Project acronym 2MoveMate4Melanoma
Project A treatment for BRAF inhibitor resistant melanoma
Researcher (PI) René BERNARDS
Host Institution (HI) STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Call Details Proof of Concept (PoC), PC1, ERC-2015-PoC
Summary Some 50% of human melanoma tumors have activating mutations in the BRAF gene. BRAF inhibitor drugs given either alone or in combination with MEK inhibitors have improved progression-free and overall survival in patients with BRAF mutant metastatic melanoma. However, drug resistance invariably limits the duration of clinical benefit of such treatments and is almost always associated with re-activation of signaling through the MAP kinase pathway in the presence of drug due to secondary mutations in the pathway. This highlights the urgent need to develop strategies to treat melanomas that have developed resistance to BRAF and/or MEK inhibitors.
As part of an ERC advanced grant, my laboratory has shown that BRAF inhibitor withdrawal in melanomas that have developed resistance to BRAF inhibitors leads to a transient growth arrest that is the consequence of temporary hyperactivation of signaling through the MAP kinase pathway, explaining the so called “drug holiday effect”. We have also found that subsequent treatment of such BRAF inhibitor resistant melanomas with Histone DeACetylase inhibitor drugs (HDACi) leads to persistent hyperactivation of MAP kinase signaling, causing both chronic proliferation arrest and cell death, ultimately leading to complete regression of BRAF-inhibitor resistant melanomas in mice.
We propose here to perform a proof of concept study in at least 10 evaluable melanoma patients that, after proven initial tumor response, have developed resistance to BRAF inhibitors to validate that subsequent treatment of such patients with an HDACi drug will result in durable responses. Translational studies on tumor biopsies taken before, during and after HDACi treatment will be performed to study the cellular effects of HDACi treatment. Our goal is to provide initial proof of concept in patients for use of this sequential BRAFi-HDACi therapy as the treatment of choice for the some 40,000 BRAF mutant melanomas that are diagnosed in the EU annually.
Summary
Some 50% of human melanoma tumors have activating mutations in the BRAF gene. BRAF inhibitor drugs given either alone or in combination with MEK inhibitors have improved progression-free and overall survival in patients with BRAF mutant metastatic melanoma. However, drug resistance invariably limits the duration of clinical benefit of such treatments and is almost always associated with re-activation of signaling through the MAP kinase pathway in the presence of drug due to secondary mutations in the pathway. This highlights the urgent need to develop strategies to treat melanomas that have developed resistance to BRAF and/or MEK inhibitors.
As part of an ERC advanced grant, my laboratory has shown that BRAF inhibitor withdrawal in melanomas that have developed resistance to BRAF inhibitors leads to a transient growth arrest that is the consequence of temporary hyperactivation of signaling through the MAP kinase pathway, explaining the so called “drug holiday effect”. We have also found that subsequent treatment of such BRAF inhibitor resistant melanomas with Histone DeACetylase inhibitor drugs (HDACi) leads to persistent hyperactivation of MAP kinase signaling, causing both chronic proliferation arrest and cell death, ultimately leading to complete regression of BRAF-inhibitor resistant melanomas in mice.
We propose here to perform a proof of concept study in at least 10 evaluable melanoma patients that, after proven initial tumor response, have developed resistance to BRAF inhibitors to validate that subsequent treatment of such patients with an HDACi drug will result in durable responses. Translational studies on tumor biopsies taken before, during and after HDACi treatment will be performed to study the cellular effects of HDACi treatment. Our goal is to provide initial proof of concept in patients for use of this sequential BRAFi-HDACi therapy as the treatment of choice for the some 40,000 BRAF mutant melanomas that are diagnosed in the EU annually.
Max ERC Funding
149 750 €
Duration
Start date: 2016-05-01, End date: 2017-10-31
Project acronym 3D-FABRIC
Project 3D Flow Analysis in Bijels Reconfigured for Interfacial Catalysis
Researcher (PI) Martin F. HAASE
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Summary
The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Max ERC Funding
1 905 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym 3D-FM
Project Taking Force Microscopy into the Third Dimension
Researcher (PI) Tjerk Hendrik Oosterkamp
Host Institution (HI) UNIVERSITEIT LEIDEN
Call Details Starting Grant (StG), PE3, ERC-2007-StG
Summary I propose to pursue two emerging Force Microscopy techniques that allow measuring structural properties below the surface of the specimen. Whereas Force Microscopy (most commonly known under the name AFM) is usually limited to measuring the surface topography and surface properties of a specimen, I will demonstrate that Force Microscopy can achieve true 3D images of the structure of the cell nucleus. In Ultrasound Force Microscopy, an ultrasound wave is launched from below towards the surface of the specimen. After the sound waves interact with structures beneath the surface of the specimen, the local variations in the amplitude and phase shift of the ultrasonic surface motion is collected by the Force Microscopy tip. Previously, measured 2D maps of the surface response have shown that the surface response is sensitive to structures below the surface. In this project I will employ miniature AFM cantilevers and nanotube tips that I have already developed in my lab. This will allow me to quickly acquire many such 2D maps at a much wider range of ultrasound frequencies and from these 2D maps calculate the full 3D structure below the surface. I expect this technique to have a resolving power better than 10 nm in three dimensions as far as 2 microns below the surface. In parallel I will introduce a major improvement to a technique based on Nuclear Magnetic Resonance (NMR). Magnetic Resonance Force Microscopy measures the interaction of a rotating nuclear spin in the field gradient of a magnetic Force Microscopy tip. However, these forces are so small that they pose an enormous challenge. Miniature cantilevers and nanotube tips, in combination with additional innovations in the detection of the cantilever motion, can overcome this problem. I expect to be able to measure the combined signal of 100 proton spins or fewer, which will allow me to measure proton densities with a resolution of 5 nm, but possibly even with atomic resolution.
Summary
I propose to pursue two emerging Force Microscopy techniques that allow measuring structural properties below the surface of the specimen. Whereas Force Microscopy (most commonly known under the name AFM) is usually limited to measuring the surface topography and surface properties of a specimen, I will demonstrate that Force Microscopy can achieve true 3D images of the structure of the cell nucleus. In Ultrasound Force Microscopy, an ultrasound wave is launched from below towards the surface of the specimen. After the sound waves interact with structures beneath the surface of the specimen, the local variations in the amplitude and phase shift of the ultrasonic surface motion is collected by the Force Microscopy tip. Previously, measured 2D maps of the surface response have shown that the surface response is sensitive to structures below the surface. In this project I will employ miniature AFM cantilevers and nanotube tips that I have already developed in my lab. This will allow me to quickly acquire many such 2D maps at a much wider range of ultrasound frequencies and from these 2D maps calculate the full 3D structure below the surface. I expect this technique to have a resolving power better than 10 nm in three dimensions as far as 2 microns below the surface. In parallel I will introduce a major improvement to a technique based on Nuclear Magnetic Resonance (NMR). Magnetic Resonance Force Microscopy measures the interaction of a rotating nuclear spin in the field gradient of a magnetic Force Microscopy tip. However, these forces are so small that they pose an enormous challenge. Miniature cantilevers and nanotube tips, in combination with additional innovations in the detection of the cantilever motion, can overcome this problem. I expect to be able to measure the combined signal of 100 proton spins or fewer, which will allow me to measure proton densities with a resolution of 5 nm, but possibly even with atomic resolution.
Max ERC Funding
1 794 960 €
Duration
Start date: 2008-08-01, End date: 2013-07-31
Project acronym 3D-JOINT
Project 3D Bioprinting of JOINT Replacements
Researcher (PI) Johannes Jos Malda
Host Institution (HI) UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Call Details Consolidator Grant (CoG), LS7, ERC-2014-CoG
Summary The world has a significant medical challenge in repairing injured or diseased joints. Joint degeneration and its related pain is a major socio-economic burden that will increase over the next decade and is currently addressed by implanting a metal prosthesis. For the long term, the ideal solution to joint injury is to successfully regenerate rather than replace the damaged cartilage with synthetic implants. Recent advances in key technologies are now bringing this “holy grail” within reach; regenerative approaches, based on cell therapy, are already clinically available albeit only for smaller focal cartilage defects.
One of these key technologies is three-dimensional (3D) bio-printing, which provides a greatly controlled placement and organization of living constructs through the layer-by-layer deposition of materials and cells. These tissue constructs can be applied as tissue models for research and screening. However, the lack of biomechanical properties of these tissue constructs has hampered their application to the regeneration of damaged, degenerated or diseased tissue.
Having established a cartilage-focussed research laboratory in the University Medical Center Utrecht, I have addressed this biomechanical limitation of hydrogels through the use of hydrogel composites. Specifically, I have pioneered a 3D bio-printing technology that combines accurately printed small diameter thermoplast filaments with cell invasive hydrogels to form strong fibre-reinforced constructs. This, in combination with bioreactor technology, is the key to the generation of larger, complex tissue constructs with cartilage-like biomechanical resilience. With 3D-JOINT I will use my in-depth bio-printing and bioreactor knowledge and experience to develop a multi-phasic 3D-printed biological replacement of the joint.
Summary
The world has a significant medical challenge in repairing injured or diseased joints. Joint degeneration and its related pain is a major socio-economic burden that will increase over the next decade and is currently addressed by implanting a metal prosthesis. For the long term, the ideal solution to joint injury is to successfully regenerate rather than replace the damaged cartilage with synthetic implants. Recent advances in key technologies are now bringing this “holy grail” within reach; regenerative approaches, based on cell therapy, are already clinically available albeit only for smaller focal cartilage defects.
One of these key technologies is three-dimensional (3D) bio-printing, which provides a greatly controlled placement and organization of living constructs through the layer-by-layer deposition of materials and cells. These tissue constructs can be applied as tissue models for research and screening. However, the lack of biomechanical properties of these tissue constructs has hampered their application to the regeneration of damaged, degenerated or diseased tissue.
Having established a cartilage-focussed research laboratory in the University Medical Center Utrecht, I have addressed this biomechanical limitation of hydrogels through the use of hydrogel composites. Specifically, I have pioneered a 3D bio-printing technology that combines accurately printed small diameter thermoplast filaments with cell invasive hydrogels to form strong fibre-reinforced constructs. This, in combination with bioreactor technology, is the key to the generation of larger, complex tissue constructs with cartilage-like biomechanical resilience. With 3D-JOINT I will use my in-depth bio-printing and bioreactor knowledge and experience to develop a multi-phasic 3D-printed biological replacement of the joint.
Max ERC Funding
1 998 871 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym 3MC
Project 3D Model Catalysts to explore new routes to sustainable fuels
Researcher (PI) Petra Elisabeth De jongh
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Consolidator Grant (CoG), PE4, ERC-2014-CoG
Summary Currently fuels, plastics, and drugs are predominantly manufactured from oil. A transition towards renewable resources critically depends on new catalysts, for instance to convert small molecules (such as solar or biomass derived hydrogen, carbon monoxide, water and carbon dioxide) into more complex ones (such as oxygenates, containing oxygen atoms in their structure). Catalyst development now often depends on trial and error rather than rational design, as the heterogeneity of these composite systems hampers detailed understanding of the role of each of the components.
I propose 3D model catalysts as a novel enabling tool to overcome this problem. Their well-defined nature allows unprecedented precision in the variation of structural parameters (morphology, spatial distribution) of the individual components, while at the same time they mimic real catalysts closely enough to allow testing under industrially relevant conditions. Using this approach I will address fundamental questions, such as:
* What are the mechanisms (structural, electronic, chemical) by which non-metal promoters influence the functionality of copper-based catalysts?
* Which nanoalloys can be formed, how does their composition influence the surface active sites and catalytic functionality under reaction conditions?
* Which size and interface effects occur, and how can we use them to tune the actitivity and selectivity towards desired products?
Our 3D model catalysts will be assembled from ordered mesoporous silica and carbon support materials and Cu-based promoted and bimetallic nanoparticles. The combination with high resolution characterization and testing under realistic conditions allows detailed insight into the role of the different components; critical for the rational design of novel catalysts for a future more sustainable production of chemicals and fuels from renewable resources.
Summary
Currently fuels, plastics, and drugs are predominantly manufactured from oil. A transition towards renewable resources critically depends on new catalysts, for instance to convert small molecules (such as solar or biomass derived hydrogen, carbon monoxide, water and carbon dioxide) into more complex ones (such as oxygenates, containing oxygen atoms in their structure). Catalyst development now often depends on trial and error rather than rational design, as the heterogeneity of these composite systems hampers detailed understanding of the role of each of the components.
I propose 3D model catalysts as a novel enabling tool to overcome this problem. Their well-defined nature allows unprecedented precision in the variation of structural parameters (morphology, spatial distribution) of the individual components, while at the same time they mimic real catalysts closely enough to allow testing under industrially relevant conditions. Using this approach I will address fundamental questions, such as:
* What are the mechanisms (structural, electronic, chemical) by which non-metal promoters influence the functionality of copper-based catalysts?
* Which nanoalloys can be formed, how does their composition influence the surface active sites and catalytic functionality under reaction conditions?
* Which size and interface effects occur, and how can we use them to tune the actitivity and selectivity towards desired products?
Our 3D model catalysts will be assembled from ordered mesoporous silica and carbon support materials and Cu-based promoted and bimetallic nanoparticles. The combination with high resolution characterization and testing under realistic conditions allows detailed insight into the role of the different components; critical for the rational design of novel catalysts for a future more sustainable production of chemicals and fuels from renewable resources.
Max ERC Funding
1 999 625 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym 4C
Project 4C technology: uncovering the multi-dimensional structure of the genome
Researcher (PI) Wouter Leonard De Laat
Host Institution (HI) KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary The architecture of DNA in the cell nucleus is an emerging epigenetic key contributor to genome function. We recently developed 4C technology, a high-throughput technique that combines state-of-the-art 3C technology with tailored micro-arrays to uniquely allow for an unbiased genome-wide search for DNA loci that interact in the nuclear space. Based on 4C technology, we were the first to provide a comprehensive overview of long-range DNA contacts of selected loci. The data showed that active and inactive chromatin domains contact many distinct regions within and between chromosomes and genes switch long-range DNA contacts in relation to their expression status. 4C technology not only allows investigating the three-dimensional structure of DNA in the nucleus, it also accurately reconstructs at least 10 megabases of the one-dimensional chromosome sequence map around the target sequence. Changes in this physical map as a result of genomic rearrangements are therefore identified by 4C technology. We recently demonstrated that 4C detects deletions, balanced inversions and translocations in patient samples at a resolution (~7kb) that allowed immediate sequencing of the breakpoints. Excitingly, 4C technology therefore offers the first high-resolution genomic approach that can identify both balanced and unbalanced genomic rearrangements. 4C is expected to become an important tool in clinical diagnosis and prognosis. Key objectives of this proposal are: 1. Explore the functional significance of DNA folding in the nucleus by systematically applying 4C technology to differentially expressed gene loci. 2. Adapt 4C technology such that it allows for massive parallel analysis of DNA interactions between regulatory elements and gene promoters. This method would greatly facilitate the identification of functionally relevant DNA elements in the genome. 3. Develop 4C technology into a clinical diagnostic tool for the accurate detection of balanced and unbalanced rearrangements.
Summary
The architecture of DNA in the cell nucleus is an emerging epigenetic key contributor to genome function. We recently developed 4C technology, a high-throughput technique that combines state-of-the-art 3C technology with tailored micro-arrays to uniquely allow for an unbiased genome-wide search for DNA loci that interact in the nuclear space. Based on 4C technology, we were the first to provide a comprehensive overview of long-range DNA contacts of selected loci. The data showed that active and inactive chromatin domains contact many distinct regions within and between chromosomes and genes switch long-range DNA contacts in relation to their expression status. 4C technology not only allows investigating the three-dimensional structure of DNA in the nucleus, it also accurately reconstructs at least 10 megabases of the one-dimensional chromosome sequence map around the target sequence. Changes in this physical map as a result of genomic rearrangements are therefore identified by 4C technology. We recently demonstrated that 4C detects deletions, balanced inversions and translocations in patient samples at a resolution (~7kb) that allowed immediate sequencing of the breakpoints. Excitingly, 4C technology therefore offers the first high-resolution genomic approach that can identify both balanced and unbalanced genomic rearrangements. 4C is expected to become an important tool in clinical diagnosis and prognosis. Key objectives of this proposal are: 1. Explore the functional significance of DNA folding in the nucleus by systematically applying 4C technology to differentially expressed gene loci. 2. Adapt 4C technology such that it allows for massive parallel analysis of DNA interactions between regulatory elements and gene promoters. This method would greatly facilitate the identification of functionally relevant DNA elements in the genome. 3. Develop 4C technology into a clinical diagnostic tool for the accurate detection of balanced and unbalanced rearrangements.
Max ERC Funding
1 225 000 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
Project acronym 4D
Project Designing Devices by Doping on Demand
Researcher (PI) Arjan HOUTEPEN
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary Electronic doping, the control over the charge carrier density, is at the heart of the success of the semiconductor industry. Promising new semiconductor materials like conductive polymers, fullerenes and quantum dots cannot be doped by traditional doping methods. The applicant and his group have developed a general method to dope these materials on demand with an electrochemical method, combined with photopolymerization of the solvents and electrolyte ions. This methods allows to precisely control the charge density in these new semiconductor materials and also allows patterning of the doping density via methods akin to photolithography used in the semiconductor industry. This enable the design of new device geometries, such as lateral pn junctions that could allow easy on chip integration of e.g. solution processable LEDs. The goal of this proof-of-concept application is to investigate the application potential of this newly developed technology. In particular it involves the development of demonstrator devices to showcase the technique’s potential, to investigate and protect the intellectual property and to analyze the interest from key industrial stakeholders in this technology. When successful, this technology has the potential to revolutionize the semiconductor industry. It could be of great economic potential and in addition may contribute to achieving sustainability goals by reducing energy consumption of lamps and displays and by offering new and improved means to harvest solar via highly efficient solution processable solar cells.
Summary
Electronic doping, the control over the charge carrier density, is at the heart of the success of the semiconductor industry. Promising new semiconductor materials like conductive polymers, fullerenes and quantum dots cannot be doped by traditional doping methods. The applicant and his group have developed a general method to dope these materials on demand with an electrochemical method, combined with photopolymerization of the solvents and electrolyte ions. This methods allows to precisely control the charge density in these new semiconductor materials and also allows patterning of the doping density via methods akin to photolithography used in the semiconductor industry. This enable the design of new device geometries, such as lateral pn junctions that could allow easy on chip integration of e.g. solution processable LEDs. The goal of this proof-of-concept application is to investigate the application potential of this newly developed technology. In particular it involves the development of demonstrator devices to showcase the technique’s potential, to investigate and protect the intellectual property and to analyze the interest from key industrial stakeholders in this technology. When successful, this technology has the potential to revolutionize the semiconductor industry. It could be of great economic potential and in addition may contribute to achieving sustainability goals by reducing energy consumption of lamps and displays and by offering new and improved means to harvest solar via highly efficient solution processable solar cells.
Max ERC Funding
150 000 €
Duration
Start date: 2019-06-01, End date: 2020-11-30
Project acronym 4D-EEG
Project 4D-EEG: A new tool to investigate the spatial and temporal activity patterns in the brain
Researcher (PI) Franciscus C.T. Van Der Helm
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Advanced Grant (AdG), PE7, ERC-2011-ADG_20110209
Summary Our first goal is to develop a new tool to determine brain activity with a high temporal (< 1 msec) and spatial (about 2 mm) resolution with the focus on motor control. High density EEG (up to 256 electrodes) will be used for EEG source localization. Advanced force-controlled robot manipulators will be used to impose continuous force perturbations to the joints. Advanced closed-loop system identification algorithms will identify the dynamic EEG response of multiple brain areas to the perturbation, leading to a functional interpretation of EEG. The propagation of the signal in time and 3D space through the cortex can be monitored: 4D-EEG. Preliminary experiments with EEG localization have shown that the continuous force perturbations resulted in a better signal-to-noise ratio and coherence than the current method using transient perturbations..
4D-EEG will be a direct measure of the neural activity in the brain with an excellent temporal response and easy to use in combination with motor control tasks. The new 4D-EEG method is expected to provide a breakthrough in comparison to functional MRI (fMRI) when elucidating the meaning of cortical map plasticity in motor learning.
Our second goal is to generate and validate new hypotheses about the longitudinal relationship between motor learning and cortical map plasticity by clinically using 4D-EEG in an intensive, repeated measurement design in patients suffering from a stroke. The application of 4D-EEG combined with haptic robots will allow us to discover how dynamics in cortical map plasticity are related with upper limb recovery after stroke in terms of neural repair and using behavioral compensation strategies while performing a meaningful motor tasks.. The non-invasive 4D-EEG technique combined with haptic robots will open the window about what and how patients (re)learn when showing motor recovery after stroke in order to allow us to develop more effective patient-tailored therapies in neuro-rehabilitation.
Summary
Our first goal is to develop a new tool to determine brain activity with a high temporal (< 1 msec) and spatial (about 2 mm) resolution with the focus on motor control. High density EEG (up to 256 electrodes) will be used for EEG source localization. Advanced force-controlled robot manipulators will be used to impose continuous force perturbations to the joints. Advanced closed-loop system identification algorithms will identify the dynamic EEG response of multiple brain areas to the perturbation, leading to a functional interpretation of EEG. The propagation of the signal in time and 3D space through the cortex can be monitored: 4D-EEG. Preliminary experiments with EEG localization have shown that the continuous force perturbations resulted in a better signal-to-noise ratio and coherence than the current method using transient perturbations..
4D-EEG will be a direct measure of the neural activity in the brain with an excellent temporal response and easy to use in combination with motor control tasks. The new 4D-EEG method is expected to provide a breakthrough in comparison to functional MRI (fMRI) when elucidating the meaning of cortical map plasticity in motor learning.
Our second goal is to generate and validate new hypotheses about the longitudinal relationship between motor learning and cortical map plasticity by clinically using 4D-EEG in an intensive, repeated measurement design in patients suffering from a stroke. The application of 4D-EEG combined with haptic robots will allow us to discover how dynamics in cortical map plasticity are related with upper limb recovery after stroke in terms of neural repair and using behavioral compensation strategies while performing a meaningful motor tasks.. The non-invasive 4D-EEG technique combined with haptic robots will open the window about what and how patients (re)learn when showing motor recovery after stroke in order to allow us to develop more effective patient-tailored therapies in neuro-rehabilitation.
Max ERC Funding
3 477 202 €
Duration
Start date: 2012-06-01, End date: 2017-05-31
Project acronym A-BINGOS
Project Accreting binary populations in Nearby Galaxies: Observations and Simulations
Researcher (PI) Andreas Zezas
Host Institution (HI) IDRYMA TECHNOLOGIAS KAI EREVNAS
Call Details Consolidator Grant (CoG), PE9, ERC-2013-CoG
Summary "High-energy observations of our Galaxy offer a good, albeit not complete, picture of the X-ray source populations, in particular the accreting binary sources. Recent ability to study accreting binaries in nearby galaxies has shown that we would be short-sighted if we restricted ourselves to our Galaxy or to a few nearby ones. I propose an ambitious project that involves a comprehensive study of all the galaxies within 10 Mpc for which we can study in detail their X-ray sources and stellar populations. The study will combine data from a unique suite of observatories (Chandra, XMM-Newton, HST, Spitzer) with state-of-the-art theoretical modelling of binary systems. I propose a novel approach that links the accreting binary populations to their parent stellar populations and surpasses any current studies of X-ray binary populations, both in scale and in scope, by: (a) combining methods and results from several different areas of astrophysics (compact objects, binary systems, stellar populations, galaxy evolution); (b) using data from almost the whole electromagnetic spectrum (infrared to X-ray bands); (c) identifying and studying the different sub-populations of accreting binaries; and (d) performing direct comparison between observations and theoretical predictions, over a broad parameter space. The project: (a) will answer the long-standing question of the formation efficiency of accreting binaries in different environments; and (b) will constrain their evolutionary paths. As by-products the project will provide eagerly awaited input to the fields of gravitational-wave sources, γ-ray bursts, and X-ray emitting galaxies at cosmological distances and it will produce a heritage multi-wavelength dataset and library of models for future studies of galaxies and accreting binaries."
Summary
"High-energy observations of our Galaxy offer a good, albeit not complete, picture of the X-ray source populations, in particular the accreting binary sources. Recent ability to study accreting binaries in nearby galaxies has shown that we would be short-sighted if we restricted ourselves to our Galaxy or to a few nearby ones. I propose an ambitious project that involves a comprehensive study of all the galaxies within 10 Mpc for which we can study in detail their X-ray sources and stellar populations. The study will combine data from a unique suite of observatories (Chandra, XMM-Newton, HST, Spitzer) with state-of-the-art theoretical modelling of binary systems. I propose a novel approach that links the accreting binary populations to their parent stellar populations and surpasses any current studies of X-ray binary populations, both in scale and in scope, by: (a) combining methods and results from several different areas of astrophysics (compact objects, binary systems, stellar populations, galaxy evolution); (b) using data from almost the whole electromagnetic spectrum (infrared to X-ray bands); (c) identifying and studying the different sub-populations of accreting binaries; and (d) performing direct comparison between observations and theoretical predictions, over a broad parameter space. The project: (a) will answer the long-standing question of the formation efficiency of accreting binaries in different environments; and (b) will constrain their evolutionary paths. As by-products the project will provide eagerly awaited input to the fields of gravitational-wave sources, γ-ray bursts, and X-ray emitting galaxies at cosmological distances and it will produce a heritage multi-wavelength dataset and library of models for future studies of galaxies and accreting binaries."
Max ERC Funding
1 242 000 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym AAATSI
Project Advanced Antenna Architecture for THZ Sensing Instruments
Researcher (PI) Andrea Neto
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Starting Grant (StG), PE7, ERC-2011-StG_20101014
Summary The Tera-Hertz portion of the spectrum presents unique potentials for advanced applications. Currently the THz spectrum is revealing the mechanisms at the origin of our universe and provides the means to monitor the health of our planet via satellite based sensing of critical gases. Potentially time domain sensing of the THz spectrum will be the ideal tool for a vast variety of medical and security applications.
Presently, systems in the THz regime are extremely expensive and consequently the THz spectrum is still the domain of only niche (expensive) scientific applications. The main problems are the lack of power and sensitivity. The wide unused THz spectral bandwidth is, herself, the only widely available resource that in the future can compensate for these problems. But, so far, when scientists try to really use the bandwidth, they run into an insurmountable physical limit: antenna dispersion. Antenna dispersion modifies the signal’s spectrum in a wavelength dependent manner in all types of radiation, but is particularly deleterious to THz signals because the spectrum is too wide and with foreseeable technology it cannot be digitized.
The goal of this proposal is to introduce break-through antenna technology that will eliminate the dispersion bottle neck and revolutionize Time Domain sensing and Spectroscopic Space Science. Achieving these goals the project will pole vault THz imaging technology into the 21-th century and develop critically important enabling technologies which will satisfy the electrical engineering needs of the next 30 years and in the long run will enable multi Tera-bit wireless communications.
In order to achieve these goals, I will first build upon two major breakthrough radiation mechanisms that I pioneered: Leaky Lenses and Connected Arrays. Eventually, ultra wide band imaging arrays constituted by thousands of components will be designed on the bases of the new theoretical findings and demonstrated.
Summary
The Tera-Hertz portion of the spectrum presents unique potentials for advanced applications. Currently the THz spectrum is revealing the mechanisms at the origin of our universe and provides the means to monitor the health of our planet via satellite based sensing of critical gases. Potentially time domain sensing of the THz spectrum will be the ideal tool for a vast variety of medical and security applications.
Presently, systems in the THz regime are extremely expensive and consequently the THz spectrum is still the domain of only niche (expensive) scientific applications. The main problems are the lack of power and sensitivity. The wide unused THz spectral bandwidth is, herself, the only widely available resource that in the future can compensate for these problems. But, so far, when scientists try to really use the bandwidth, they run into an insurmountable physical limit: antenna dispersion. Antenna dispersion modifies the signal’s spectrum in a wavelength dependent manner in all types of radiation, but is particularly deleterious to THz signals because the spectrum is too wide and with foreseeable technology it cannot be digitized.
The goal of this proposal is to introduce break-through antenna technology that will eliminate the dispersion bottle neck and revolutionize Time Domain sensing and Spectroscopic Space Science. Achieving these goals the project will pole vault THz imaging technology into the 21-th century and develop critically important enabling technologies which will satisfy the electrical engineering needs of the next 30 years and in the long run will enable multi Tera-bit wireless communications.
In order to achieve these goals, I will first build upon two major breakthrough radiation mechanisms that I pioneered: Leaky Lenses and Connected Arrays. Eventually, ultra wide band imaging arrays constituted by thousands of components will be designed on the bases of the new theoretical findings and demonstrated.
Max ERC Funding
1 499 487 €
Duration
Start date: 2011-11-01, End date: 2017-10-31
Project acronym AARTFAAC
Project Amsterdam-ASTRON Radio Transient Facility And Analysis Centre: Probing the Extremes of Astrophysics
Researcher (PI) Ralph Antoine Marie Joseph Wijers
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), PE9, ERC-2009-AdG
Summary Some of the most extreme tests of physical law come from its manifestations in the behaviour of black holes and neutron stars, and as such these objects should be used as fundamental physics labs. Due to advances in both theoretical work and observational techniques, I have a major opportunity now to significantly push this agenda forward and get better answers to questions like: How are black holes born? How can energy be extracted from black holes? What is the origin of magnetic fields and cosmic rays in jets and shocks? Is their primary energy stream hadronic or magnetic? I propose to do this by exploiting the advent of wide-field radio astronomy: extreme objects are very rare and usually transient, so not only must one survey large areas of sky, but also must one do this often. I propose to form and shape a group that will use the LOFAR wide-field radio telescope to hunt for these extreme transients and systematically collect enough well-documented examples of the behaviour of each type of transient. Furthermore, I propose to expand LOFAR with a true 24/7 all-sky monitor to catch and study even the rarest of events. Next, I will use my experience in gamma-ray burst followup to conduct a vigorous multi-wavelength programme of study of these objects, to constrain their physics from as many angles as possible. This will eventually include results from multi-messenger astrophysics, in which we use neutrinos, gravity waves, and other non-electromagnetic messengers as extra diagnostics of the physics of these sources. Finally, I will build on my experience in modelling accretion phenomena and relativistic explosions to develop a theoretical framework for these phenomena and constrain the resulting models with the rich data sets we obtain.
Summary
Some of the most extreme tests of physical law come from its manifestations in the behaviour of black holes and neutron stars, and as such these objects should be used as fundamental physics labs. Due to advances in both theoretical work and observational techniques, I have a major opportunity now to significantly push this agenda forward and get better answers to questions like: How are black holes born? How can energy be extracted from black holes? What is the origin of magnetic fields and cosmic rays in jets and shocks? Is their primary energy stream hadronic or magnetic? I propose to do this by exploiting the advent of wide-field radio astronomy: extreme objects are very rare and usually transient, so not only must one survey large areas of sky, but also must one do this often. I propose to form and shape a group that will use the LOFAR wide-field radio telescope to hunt for these extreme transients and systematically collect enough well-documented examples of the behaviour of each type of transient. Furthermore, I propose to expand LOFAR with a true 24/7 all-sky monitor to catch and study even the rarest of events. Next, I will use my experience in gamma-ray burst followup to conduct a vigorous multi-wavelength programme of study of these objects, to constrain their physics from as many angles as possible. This will eventually include results from multi-messenger astrophysics, in which we use neutrinos, gravity waves, and other non-electromagnetic messengers as extra diagnostics of the physics of these sources. Finally, I will build on my experience in modelling accretion phenomena and relativistic explosions to develop a theoretical framework for these phenomena and constrain the resulting models with the rich data sets we obtain.
Max ERC Funding
3 499 128 €
Duration
Start date: 2010-10-01, End date: 2016-09-30
Project acronym ABCTRANSPORT
Project Minimalist multipurpose ATP-binding cassette transporters
Researcher (PI) Dirk Jan Slotboom
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary Many Gram-positive (pathogenic) bacteria are dependent on the uptake of vitamins from the environment or from the infected host. We have recently discovered the long-elusive family of membrane protein complexes catalyzing such transport. The vitamin transporters have an unprecedented modular architecture consisting of a single multipurpose energizing module (the Energy Coupling Factor, ECF) and multiple exchangeable membrane proteins responsible for substrate recognition (S-components). The S-components have characteristics of ion-gradient driven transporters (secondary active transporters), whereas the energizing modules are related to ATP-binding cassette (ABC) transporters (primary active transporters).
The aim of the proposal is threefold: First, we will address the question how properties of primary and secondary transporters are combined in ECF transporters to obtain a novel transport mechanism. Second, we will study the fundamental and unresolved question how protein-protein recognition takes place in the hydrophobic environment of the lipid bilayer. The modular nature of the ECF proteins offers a natural system to study the driving forces used for membrane protein interaction. Third, we will assess whether the ECF transport systems could become targets for antibacterial drugs. ECF transporters are found exclusively in prokaryotes, and their activity is often essential for viability of Gram-positive pathogens. Thus they could turn out to be an Achilles’ heel for the organisms.
Structural and mechanistic studies (X-ray crystallography, microscopy, spectroscopy and biochemistry) will reveal how the different transport modes are combined in a single protein complex, how transport is energized and catalyzed, and how protein-protein recognition takes place. Microbiological screens will be developed to search for compounds that inhibit prokaryote-specific steps of the mechanism of ECF transporters.
Summary
Many Gram-positive (pathogenic) bacteria are dependent on the uptake of vitamins from the environment or from the infected host. We have recently discovered the long-elusive family of membrane protein complexes catalyzing such transport. The vitamin transporters have an unprecedented modular architecture consisting of a single multipurpose energizing module (the Energy Coupling Factor, ECF) and multiple exchangeable membrane proteins responsible for substrate recognition (S-components). The S-components have characteristics of ion-gradient driven transporters (secondary active transporters), whereas the energizing modules are related to ATP-binding cassette (ABC) transporters (primary active transporters).
The aim of the proposal is threefold: First, we will address the question how properties of primary and secondary transporters are combined in ECF transporters to obtain a novel transport mechanism. Second, we will study the fundamental and unresolved question how protein-protein recognition takes place in the hydrophobic environment of the lipid bilayer. The modular nature of the ECF proteins offers a natural system to study the driving forces used for membrane protein interaction. Third, we will assess whether the ECF transport systems could become targets for antibacterial drugs. ECF transporters are found exclusively in prokaryotes, and their activity is often essential for viability of Gram-positive pathogens. Thus they could turn out to be an Achilles’ heel for the organisms.
Structural and mechanistic studies (X-ray crystallography, microscopy, spectroscopy and biochemistry) will reveal how the different transport modes are combined in a single protein complex, how transport is energized and catalyzed, and how protein-protein recognition takes place. Microbiological screens will be developed to search for compounds that inhibit prokaryote-specific steps of the mechanism of ECF transporters.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-01-01, End date: 2017-12-31
Project acronym ABCvolume
Project The ABC of Cell Volume Regulation
Researcher (PI) Berend Poolman
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Advanced Grant (AdG), LS1, ERC-2014-ADG
Summary Cell volume regulation is crucial for any living cell because changes in volume determine the metabolic activity through e.g. changes in ionic strength, pH, macromolecular crowding and membrane tension. These physical chemical parameters influence interaction rates and affinities of biomolecules, folding rates, and fold stabilities in vivo. Understanding of the underlying volume regulatory mechanisms has immediate application in biotechnology and health, yet these factors are generally ignored in systems analyses of cellular functions.
My team has uncovered a number of mechanisms and insights of cell volume regulation. The next step forward is to elucidate how the components of a cell volume regulatory circuit work together and control the physicochemical conditions of the cell.
I propose construction of a synthetic cell in which an osmoregulatory transporter and mechanosensitive channel form a minimal volume regulatory network. My group has developed the technology to reconstitute membrane proteins into lipid vesicles (synthetic cells). One of the challenges is to incorporate into the vesicles an efficient pathway for ATP production and maintain energy homeostasis while the load on the system varies. We aim to control the transmembrane flux of osmolytes, which requires elucidation of the molecular mechanism of gating of the osmoregulatory transporter. We will focus on the glycine betaine ABC importer, which is one of the most complex transporters known to date with ten distinct protein domains, transiently interacting with each other.
The proposed synthetic metabolic circuit constitutes a fascinating out-of-equilibrium system, allowing us to understand cell volume regulatory mechanisms in a context and at a level of complexity minimally needed for life. Analysis of this circuit will address many outstanding questions and eventually allow us to design more sophisticated vesicular systems with applications, for example as compartmentalized reaction networks.
Summary
Cell volume regulation is crucial for any living cell because changes in volume determine the metabolic activity through e.g. changes in ionic strength, pH, macromolecular crowding and membrane tension. These physical chemical parameters influence interaction rates and affinities of biomolecules, folding rates, and fold stabilities in vivo. Understanding of the underlying volume regulatory mechanisms has immediate application in biotechnology and health, yet these factors are generally ignored in systems analyses of cellular functions.
My team has uncovered a number of mechanisms and insights of cell volume regulation. The next step forward is to elucidate how the components of a cell volume regulatory circuit work together and control the physicochemical conditions of the cell.
I propose construction of a synthetic cell in which an osmoregulatory transporter and mechanosensitive channel form a minimal volume regulatory network. My group has developed the technology to reconstitute membrane proteins into lipid vesicles (synthetic cells). One of the challenges is to incorporate into the vesicles an efficient pathway for ATP production and maintain energy homeostasis while the load on the system varies. We aim to control the transmembrane flux of osmolytes, which requires elucidation of the molecular mechanism of gating of the osmoregulatory transporter. We will focus on the glycine betaine ABC importer, which is one of the most complex transporters known to date with ten distinct protein domains, transiently interacting with each other.
The proposed synthetic metabolic circuit constitutes a fascinating out-of-equilibrium system, allowing us to understand cell volume regulatory mechanisms in a context and at a level of complexity minimally needed for life. Analysis of this circuit will address many outstanding questions and eventually allow us to design more sophisticated vesicular systems with applications, for example as compartmentalized reaction networks.
Max ERC Funding
2 247 231 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym ABSENS
Project Exploring the diagnostics market for simple and fast point-of-care antibody detection
Researcher (PI) M MERKX
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary Antibody detection assays are used in many fields of biomedicine including the diagnosis of infectious diseases, autoimmune diseases and allergies. Current analytical techniques for antibody detection come with intrinsic limitations such as the requirement for multiple time-consuming incubation steps, multiple reagents, and/or sophisticated equipment. Supported by an ERC consolidator grant we have developed a highly modular sensor concept for antibody-responsive reporter enzymes (AbSens) that addresses many of these challenges. Key advantages include the ability to monitor antibodies directly in solution, easy read-out based on a simple color reaction, adaptability to target any antibody of interest, and high affinity and specificity. We believe that this generic sensor platform could find applications in low-cost point-of-care diagnostics, clinical research, and the development of therapeutic antibodies.
The goal of AbSens is to identify those opportunities in the huge market of antibody-based diagnostics where our sensor platform provides unique advantages over existing technologies, both in terms of analytical performance and economics.
To enable the next step towards commercialization, the analytical performance of our technology will be compared to current gold standards using relevant clinical samples in collaboration with commercial parties and clinicians. Other commercially important parameters are the long-term stability of the assay components and the development of a yeast-based production system to lower the cost of enzyme production. Based on an in-depth market analysis and the feedback we receive from external stakeholders on the performance of our technology, a realistic strategy will be developed for the further commercialization. In anticipation of exploring the commercialization of our AbSens technology we filed a US provisional patent application in Sept. 2012 on the key underlying technology, which was recently continued via the PCT route.
Summary
Antibody detection assays are used in many fields of biomedicine including the diagnosis of infectious diseases, autoimmune diseases and allergies. Current analytical techniques for antibody detection come with intrinsic limitations such as the requirement for multiple time-consuming incubation steps, multiple reagents, and/or sophisticated equipment. Supported by an ERC consolidator grant we have developed a highly modular sensor concept for antibody-responsive reporter enzymes (AbSens) that addresses many of these challenges. Key advantages include the ability to monitor antibodies directly in solution, easy read-out based on a simple color reaction, adaptability to target any antibody of interest, and high affinity and specificity. We believe that this generic sensor platform could find applications in low-cost point-of-care diagnostics, clinical research, and the development of therapeutic antibodies.
The goal of AbSens is to identify those opportunities in the huge market of antibody-based diagnostics where our sensor platform provides unique advantages over existing technologies, both in terms of analytical performance and economics.
To enable the next step towards commercialization, the analytical performance of our technology will be compared to current gold standards using relevant clinical samples in collaboration with commercial parties and clinicians. Other commercially important parameters are the long-term stability of the assay components and the development of a yeast-based production system to lower the cost of enzyme production. Based on an in-depth market analysis and the feedback we receive from external stakeholders on the performance of our technology, a realistic strategy will be developed for the further commercialization. In anticipation of exploring the commercialization of our AbSens technology we filed a US provisional patent application in Sept. 2012 on the key underlying technology, which was recently continued via the PCT route.
Max ERC Funding
150 000 €
Duration
Start date: 2014-09-01, End date: 2015-08-31
Project acronym ACOFORS
Project Launching Acoustic Force Spectroscopy - unlocking the potential of biomolecular bungee jumping
Researcher (PI) Gijs Jan Lodewijk Wuite
Host Institution (HI) STICHTING VU
Call Details Proof of Concept (PoC), PC1, ERC-2014-PoC
Summary ACOFORS has been designed with the ultimate goal of preparing commercialisation of Acoustic Force Spectroscopy (AFS). AFS is a completely new and powerful technique for determining biomolecular mechanics and structure of single molecules such as DNA and proteins. These studies are performed on a large scale by biologists and within pharmaceutical companies for e.g. drug discovery and development. Current technologies for force spectroscopy (FS) represent a $50+ million market, but are expensive, require high levels of specialism and are laborious. AFS, invented in the laboratory of Prof. Wuite, is much simpler to use, can be operated in high-throughput mode and can become available at relative low cost. As such, AFS vastly expands the possibilities of FS and makes it available to a much wider community. This makes AFS a very attractive technology for science and business, both from the perspective of the user and of the seller.
In ACOFORS, a team of scientists and business developers will transform the current prototype in a marketable product, strengthen the intellectual property position, build a solid business case based on an extensive market analysis and take steps towards licensing the technology to industry.
Summary
ACOFORS has been designed with the ultimate goal of preparing commercialisation of Acoustic Force Spectroscopy (AFS). AFS is a completely new and powerful technique for determining biomolecular mechanics and structure of single molecules such as DNA and proteins. These studies are performed on a large scale by biologists and within pharmaceutical companies for e.g. drug discovery and development. Current technologies for force spectroscopy (FS) represent a $50+ million market, but are expensive, require high levels of specialism and are laborious. AFS, invented in the laboratory of Prof. Wuite, is much simpler to use, can be operated in high-throughput mode and can become available at relative low cost. As such, AFS vastly expands the possibilities of FS and makes it available to a much wider community. This makes AFS a very attractive technology for science and business, both from the perspective of the user and of the seller.
In ACOFORS, a team of scientists and business developers will transform the current prototype in a marketable product, strengthen the intellectual property position, build a solid business case based on an extensive market analysis and take steps towards licensing the technology to industry.
Max ERC Funding
150 000 €
Duration
Start date: 2015-07-01, End date: 2016-06-30
Project acronym ACOM
Project Commercial feasibility of microbial therapy
Researcher (PI) Willem Meindert DE VOS
Host Institution (HI) WAGENINGEN UNIVERSITY
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary Our body is colonized by complex microbial communities (our microbiome) that are most abundant in the intestinal tract where they contribute significantly to our health and disease. It has been established that aberrations in our microbiome are of particular importance in obesity, type 2 diabetes and metabolic syndrome, rapidly growing diseases with a drug market volume of over 5 B$ per year. We have discovered in the ERC project Microbes Inside that a particular bacterium is able to modify the intestinal microbiome and may be used to develop a new approach to treat these and other metabolic diseases. The Proof of Concept project ACOM aims to confirm the commercial and technological feasibility of this approach, consolidate and expand our IP position, and develop a product development plan. These form the elements of a business plan that is expected to result in establishing a spin out company (ACOM).
Summary
Our body is colonized by complex microbial communities (our microbiome) that are most abundant in the intestinal tract where they contribute significantly to our health and disease. It has been established that aberrations in our microbiome are of particular importance in obesity, type 2 diabetes and metabolic syndrome, rapidly growing diseases with a drug market volume of over 5 B$ per year. We have discovered in the ERC project Microbes Inside that a particular bacterium is able to modify the intestinal microbiome and may be used to develop a new approach to treat these and other metabolic diseases. The Proof of Concept project ACOM aims to confirm the commercial and technological feasibility of this approach, consolidate and expand our IP position, and develop a product development plan. These form the elements of a business plan that is expected to result in establishing a spin out company (ACOM).
Max ERC Funding
142 000 €
Duration
Start date: 2014-06-01, End date: 2015-05-31
Project acronym ACTIVATION OF XCI
Project Molecular mechanisms controlling X chromosome inactivation
Researcher (PI) Joost Henk Gribnau
Host Institution (HI) ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary In mammals, gene dosage of X-chromosomal genes is equalized between sexes by random inactivation of either one of the two X chromosomes in female cells. In the initial phase of X chromosome inactivation (XCI), a counting and initiation process determines the number of X chromosomes per nucleus, and elects the future inactive X chromosome (Xi). Xist is an X-encoded gene that plays a crucial role in the XCI process. At the start of XCI Xist expression is up-regulated and Xist RNA accumulates on the future Xi thereby initiating silencing in cis. Recent work performed in my laboratory indicates that the counting and initiation process is directed by a stochastic mechanism, in which each X chromosome has an independent probability to be inactivated. We also found that this probability is determined by the X:ploïdy ratio. These results indicated the presence of at least one X-linked activator of XCI. With a BAC screen we recently identified X-encoded RNF12 to be a dose-dependent activator of XCI. Expression of RNF12 correlates with Xist expression, and a heterozygous deletion of Rnf12 results in a marked loss of XCI in female cells. The presence of a small proportion of cells that still initiate XCI, in Rnf12+/- cells, also indicated that more XCI-activators are involved in XCI. Here, we propose to investigate the molecular mechanism by which RNF12 activates XCI in mouse and human, and to search for additional XCI-activators. We will also attempt to establish the role of different inhibitors of XCI, including CTCF and the pluripotency factors OCT4, SOX2 and NANOG. We anticipate that these studies will significantly advance our understanding of XCI mechanisms, which is highly relevant for a better insight in the manifestation of X-linked diseases that are affected by XCI.
Summary
In mammals, gene dosage of X-chromosomal genes is equalized between sexes by random inactivation of either one of the two X chromosomes in female cells. In the initial phase of X chromosome inactivation (XCI), a counting and initiation process determines the number of X chromosomes per nucleus, and elects the future inactive X chromosome (Xi). Xist is an X-encoded gene that plays a crucial role in the XCI process. At the start of XCI Xist expression is up-regulated and Xist RNA accumulates on the future Xi thereby initiating silencing in cis. Recent work performed in my laboratory indicates that the counting and initiation process is directed by a stochastic mechanism, in which each X chromosome has an independent probability to be inactivated. We also found that this probability is determined by the X:ploïdy ratio. These results indicated the presence of at least one X-linked activator of XCI. With a BAC screen we recently identified X-encoded RNF12 to be a dose-dependent activator of XCI. Expression of RNF12 correlates with Xist expression, and a heterozygous deletion of Rnf12 results in a marked loss of XCI in female cells. The presence of a small proportion of cells that still initiate XCI, in Rnf12+/- cells, also indicated that more XCI-activators are involved in XCI. Here, we propose to investigate the molecular mechanism by which RNF12 activates XCI in mouse and human, and to search for additional XCI-activators. We will also attempt to establish the role of different inhibitors of XCI, including CTCF and the pluripotency factors OCT4, SOX2 and NANOG. We anticipate that these studies will significantly advance our understanding of XCI mechanisms, which is highly relevant for a better insight in the manifestation of X-linked diseases that are affected by XCI.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym ActiveBioFluids
Project Origins of Collective Motion in Active Biofluids
Researcher (PI) Daniel TAM
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary The emergence of coherent behaviour is ubiquitous in the natural world and has long captivated biologists and physicists alike. One area of growing interest is the collective motion and synchronization arising within and between simple motile organisms. My goal is to develop and use a novel experimental approach to unravel the origins of spontaneous coherent motion in three model systems of biofluids: (1) the synchronization of the two flagella of green algae Chlamydomonas Rheinhardtii, (2) the metachronal wave in the cilia of protist Paramecium and (3) the collective motion of swimming microorganisms in active suspensions. Understanding the mechanisms leading to collective motion is of tremendous importance because it is crucial to many biological processes such as mechanical signal transduction, embryonic development and biofilm formation.
Up till now, most of the work has been theoretical and has led to the dominant view that hydrodynamic interactions are the main driving force for synchronization and collective motion. Recent experiments have challenged this view and highlighted the importance of direct mechanical contact. New experimental studies are now crucially needed. The state-of-the-art of experimental approaches consists of observations of unperturbed cells. The key innovation in our approach is to dynamically interact with microorganisms in real-time, at the relevant time and length scales. I will investigate the origins of coherent motion by reproducing synthetically the mechanical signatures of physiological flows and direct mechanical interactions and track precisely the response of the organism to the perturbations. Our new approach will incorporate optical tweezers to interact with motile cells, and a unique μ-Tomographic PIV setup to track their 3D micron-scale motion.
This proposal tackles a timely question in biophysics and will yield new insight into the fundamental principles underlying collective motion in active biological matter.
Summary
The emergence of coherent behaviour is ubiquitous in the natural world and has long captivated biologists and physicists alike. One area of growing interest is the collective motion and synchronization arising within and between simple motile organisms. My goal is to develop and use a novel experimental approach to unravel the origins of spontaneous coherent motion in three model systems of biofluids: (1) the synchronization of the two flagella of green algae Chlamydomonas Rheinhardtii, (2) the metachronal wave in the cilia of protist Paramecium and (3) the collective motion of swimming microorganisms in active suspensions. Understanding the mechanisms leading to collective motion is of tremendous importance because it is crucial to many biological processes such as mechanical signal transduction, embryonic development and biofilm formation.
Up till now, most of the work has been theoretical and has led to the dominant view that hydrodynamic interactions are the main driving force for synchronization and collective motion. Recent experiments have challenged this view and highlighted the importance of direct mechanical contact. New experimental studies are now crucially needed. The state-of-the-art of experimental approaches consists of observations of unperturbed cells. The key innovation in our approach is to dynamically interact with microorganisms in real-time, at the relevant time and length scales. I will investigate the origins of coherent motion by reproducing synthetically the mechanical signatures of physiological flows and direct mechanical interactions and track precisely the response of the organism to the perturbations. Our new approach will incorporate optical tweezers to interact with motile cells, and a unique μ-Tomographic PIV setup to track their 3D micron-scale motion.
This proposal tackles a timely question in biophysics and will yield new insight into the fundamental principles underlying collective motion in active biological matter.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym ACUITY
Project Algorithms for coping with uncertainty and intractability
Researcher (PI) Nikhil Bansal
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Call Details Consolidator Grant (CoG), PE6, ERC-2013-CoG
Summary The two biggest challenges in solving practical optimization problems are computational intractability, and the presence
of uncertainty: most problems are either NP-hard, or have incomplete input data which
makes an exact computation impossible.
Recently, there has been a huge progress in our understanding of intractability, based on spectacular algorithmic and lower bound techniques. For several problems, especially those with only local constraints, we can design optimum
approximation algorithms that are provably the best possible.
However, typical optimization problems usually involve complex global constraints and are much less understood. The situation is even worse for coping with uncertainty. Most of the algorithms are based on ad-hoc techniques and there is no deeper understanding of what makes various problems easy or hard.
This proposal describes several new directions, together with concrete intermediate goals, that will break important new ground in the theory of approximation and online algorithms. The particular directions we consider are (i) extend the primal dual method to systematically design online algorithms, (ii) build a structural theory of online problems based on work functions, (iii) develop new tools to use the power of strong convex relaxations and (iv) design new algorithmic approaches based on non-constructive proof techniques.
The proposed research is at the
cutting edge of algorithm design, and builds upon the recent success of the PI in resolving several longstanding questions in these areas. Any progress is likely to be a significant contribution to theoretical
computer science and combinatorial optimization.
Summary
The two biggest challenges in solving practical optimization problems are computational intractability, and the presence
of uncertainty: most problems are either NP-hard, or have incomplete input data which
makes an exact computation impossible.
Recently, there has been a huge progress in our understanding of intractability, based on spectacular algorithmic and lower bound techniques. For several problems, especially those with only local constraints, we can design optimum
approximation algorithms that are provably the best possible.
However, typical optimization problems usually involve complex global constraints and are much less understood. The situation is even worse for coping with uncertainty. Most of the algorithms are based on ad-hoc techniques and there is no deeper understanding of what makes various problems easy or hard.
This proposal describes several new directions, together with concrete intermediate goals, that will break important new ground in the theory of approximation and online algorithms. The particular directions we consider are (i) extend the primal dual method to systematically design online algorithms, (ii) build a structural theory of online problems based on work functions, (iii) develop new tools to use the power of strong convex relaxations and (iv) design new algorithmic approaches based on non-constructive proof techniques.
The proposed research is at the
cutting edge of algorithm design, and builds upon the recent success of the PI in resolving several longstanding questions in these areas. Any progress is likely to be a significant contribution to theoretical
computer science and combinatorial optimization.
Max ERC Funding
1 519 285 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym AD-HOC
Project Artificial Dielectrics for High-frequency On-Chip antennas
Researcher (PI) Andrea Neto
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Proof of Concept (PoC), PC1, ERC-2015-PoC
Summary High-speed wireless communication and automotive radars are two applications with huge social and market potentials that can be revolutionized by the development of high-frequency (sub-terahertz) technology. Despite the recent advances in low-cost integrated circuits, the poor performance of on-chip antennas is nowadays the major bottleneck in converting the electrical signals (on-chip) into radiated ones (off-chip). For decades the problem of “surface waves” has prevented the efficient use of radiators on chip.
The AD-HOC project aims at exploiting the breakthrough technology of Artificial Dielectric (AD) layers as the solution to the surface-wave problem of High-frequency On-Chip antennas. The processes necessary to micro-fabricate AD layers will be optimized with the goal of achieving reliable manufacturing, while offering design flexibility at low costs. This will allow the wide exploitation of the AD layers, as they can be used by industrial technology providers as add-on components to at least double the efficiency of their integrated circuit front ends.
By overcoming the fundamental limitation of integrated antennas, AD layers have high potential to become a “standard” component in all future car-safety and wireless-communication devices. The AD-HOC project will bring this innovative technology to a pre-demonstration stage to strengthen commercialization and scaling-up opportunities.
Summary
High-speed wireless communication and automotive radars are two applications with huge social and market potentials that can be revolutionized by the development of high-frequency (sub-terahertz) technology. Despite the recent advances in low-cost integrated circuits, the poor performance of on-chip antennas is nowadays the major bottleneck in converting the electrical signals (on-chip) into radiated ones (off-chip). For decades the problem of “surface waves” has prevented the efficient use of radiators on chip.
The AD-HOC project aims at exploiting the breakthrough technology of Artificial Dielectric (AD) layers as the solution to the surface-wave problem of High-frequency On-Chip antennas. The processes necessary to micro-fabricate AD layers will be optimized with the goal of achieving reliable manufacturing, while offering design flexibility at low costs. This will allow the wide exploitation of the AD layers, as they can be used by industrial technology providers as add-on components to at least double the efficiency of their integrated circuit front ends.
By overcoming the fundamental limitation of integrated antennas, AD layers have high potential to become a “standard” component in all future car-safety and wireless-communication devices. The AD-HOC project will bring this innovative technology to a pre-demonstration stage to strengthen commercialization and scaling-up opportunities.
Max ERC Funding
150 000 €
Duration
Start date: 2016-09-01, End date: 2018-02-28
Project acronym AdaptiveResponse
Project The evolution of adaptive response mechanisms
Researcher (PI) Franz WEISSING
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Advanced Grant (AdG), LS8, ERC-2017-ADG
Summary In an era of rapid climate change there is a pressing need to understand whether and how organisms are able to adapt to novel environments. Such understanding is hampered by a major divide in the life sciences. Disciplines like systems biology or neurobiology make rapid progress in unravelling the mechanisms underlying the responses of organisms to their environment, but this knowledge is insufficiently integrated in eco-evolutionary theory. Current eco-evolutionary models focus on the response patterns themselves, largely neglecting the structures and mechanisms producing these patterns. Here I propose a new, mechanism-oriented framework that views the architecture of adaptation, rather than the resulting responses, as the primary target of natural selection. I am convinced that this change in perspective will yield fundamentally new insights, necessitating the re-evaluation of many seemingly well-established eco-evolutionary principles.
My aim is to develop a comprehensive theory of the eco-evolutionary causes and consequences of the architecture underlying adaptive responses. In three parallel lines of investigation, I will study how architecture is shaped by selection, how evolved response strategies reflect the underlying architecture, and how these responses affect the eco-evolutionary dynamics and the capacity to adapt to novel conditions. All three lines have the potential of making ground-breaking contributions to eco-evolutionary theory, including: the specification of evolutionary tipping points; resolving the puzzle that real organisms evolve much faster than predicted by current theory; a new and general explanation for the evolutionary emergence of individual variation; and a framework for studying the evolution of learning and other general-purpose mechanisms. By making use of concepts from information theory and artificial intelligence, the project will also introduce various methodological innovations.
Summary
In an era of rapid climate change there is a pressing need to understand whether and how organisms are able to adapt to novel environments. Such understanding is hampered by a major divide in the life sciences. Disciplines like systems biology or neurobiology make rapid progress in unravelling the mechanisms underlying the responses of organisms to their environment, but this knowledge is insufficiently integrated in eco-evolutionary theory. Current eco-evolutionary models focus on the response patterns themselves, largely neglecting the structures and mechanisms producing these patterns. Here I propose a new, mechanism-oriented framework that views the architecture of adaptation, rather than the resulting responses, as the primary target of natural selection. I am convinced that this change in perspective will yield fundamentally new insights, necessitating the re-evaluation of many seemingly well-established eco-evolutionary principles.
My aim is to develop a comprehensive theory of the eco-evolutionary causes and consequences of the architecture underlying adaptive responses. In three parallel lines of investigation, I will study how architecture is shaped by selection, how evolved response strategies reflect the underlying architecture, and how these responses affect the eco-evolutionary dynamics and the capacity to adapt to novel conditions. All three lines have the potential of making ground-breaking contributions to eco-evolutionary theory, including: the specification of evolutionary tipping points; resolving the puzzle that real organisms evolve much faster than predicted by current theory; a new and general explanation for the evolutionary emergence of individual variation; and a framework for studying the evolution of learning and other general-purpose mechanisms. By making use of concepts from information theory and artificial intelligence, the project will also introduce various methodological innovations.
Max ERC Funding
2 500 000 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym ADAPTIVES
Project Algorithmic Development and Analysis of Pioneer Techniques for Imaging with waVES
Researcher (PI) Chrysoula Tsogka
Host Institution (HI) IDRYMA TECHNOLOGIAS KAI EREVNAS
Call Details Starting Grant (StG), PE1, ERC-2009-StG
Summary The proposed work concerns the theoretical and numerical development of robust and adaptive methodologies for broadband imaging in clutter. The word clutter expresses our uncertainty on the wave speed of the propagation medium. Our results are expected to have a strong impact in a wide range of applications, including underwater acoustics, exploration geophysics and ultrasound non-destructive testing. Our machinery is coherent interferometry (CINT), a state-of-the-art statistically stable imaging methodology, highly suitable for the development of imaging methods in clutter. We aim to extend CINT along two complementary directions: novel types of applications, and further mathematical and numerical development so as to assess and extend its range of applicability. CINT is designed for imaging with partially coherent array data recorded in richly scattering media. It uses statistical smoothing techniques to obtain results that are independent of the clutter realization. Quantifying the amount of smoothing needed is difficult, especially when there is no a priori knowledge about the propagation medium. We intend to address this question by coupling the imaging process with the estimation of the medium's large scale features. Our algorithms rely on the residual coherence in the data. When the coherent signal is too weak, the CINT results are unsatisfactory. We propose two ways for enhancing the resolution of CINT: filter the data prior to imaging (noise reduction) and waveform design (optimize the source distribution). Finally, we propose to extend the applicability of our imaging-in-clutter methodologies by investigating the possibility of utilizing ambient noise sources to perform passive sensor imaging, as well as by studying the imaging problem in random waveguides.
Summary
The proposed work concerns the theoretical and numerical development of robust and adaptive methodologies for broadband imaging in clutter. The word clutter expresses our uncertainty on the wave speed of the propagation medium. Our results are expected to have a strong impact in a wide range of applications, including underwater acoustics, exploration geophysics and ultrasound non-destructive testing. Our machinery is coherent interferometry (CINT), a state-of-the-art statistically stable imaging methodology, highly suitable for the development of imaging methods in clutter. We aim to extend CINT along two complementary directions: novel types of applications, and further mathematical and numerical development so as to assess and extend its range of applicability. CINT is designed for imaging with partially coherent array data recorded in richly scattering media. It uses statistical smoothing techniques to obtain results that are independent of the clutter realization. Quantifying the amount of smoothing needed is difficult, especially when there is no a priori knowledge about the propagation medium. We intend to address this question by coupling the imaging process with the estimation of the medium's large scale features. Our algorithms rely on the residual coherence in the data. When the coherent signal is too weak, the CINT results are unsatisfactory. We propose two ways for enhancing the resolution of CINT: filter the data prior to imaging (noise reduction) and waveform design (optimize the source distribution). Finally, we propose to extend the applicability of our imaging-in-clutter methodologies by investigating the possibility of utilizing ambient noise sources to perform passive sensor imaging, as well as by studying the imaging problem in random waveguides.
Max ERC Funding
690 000 €
Duration
Start date: 2010-06-01, End date: 2015-11-30
Project acronym ADDICTION
Project Beyond the Genetics of Addiction
Researcher (PI) Jacqueline Mignon Vink
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Starting Grant (StG), SH4, ERC-2011-StG_20101124
Summary My proposal seeks to explain the complex interplay between genetic and environmental causes of individual variation in substance use and the risk for abuse. Substance use is common. Substances like nicotine and cannabis have well-known negative health consequences, while alcohol and caffeine use may be both beneficial and detrimental, depending on quantity and frequency of use. Twin studies (including my own) demonstrated that both heritable and environmental factors play a role.
My proposal on substance use (nicotine, alcohol, cannabis and caffeine) is organized around several key objectives: 1. To unravel the complex contribution of genetic and environmental factors to substance use by using extended twin family designs; 2. To identify and confirm genes and gene networks involved in substance use by using DNA-variant data; 3. To explore gene expression patterns with RNA data in substance users versus non-users; 4. To investigate biomarkers in substance users versus non-users using blood or urine; 5. To unravel relation between substance use and health by linking twin-family data to national medical databases.
To realize these aims I will use the extensive resources of the Netherlands Twin Register (NTR); including both the longitudinal phenotype database and the biological samples. I have been involved in data collection, coordination of data collection and analyzing NTR data since 1999. With my comprehensive experience in data collection, data analyses and my knowledge in the field of behavior genetics and addiction research I will be able to successfully lead this cutting-edge project. Additional data crucial for the project will be collected by my team. Large samples will be available for this study and state-of-the art methods will be used to analyze the data. All together, my project will offer powerful approaches to unravel the complex interaction between genetic and environmental causes of individual differences in substance use and the risk for abuse.
Summary
My proposal seeks to explain the complex interplay between genetic and environmental causes of individual variation in substance use and the risk for abuse. Substance use is common. Substances like nicotine and cannabis have well-known negative health consequences, while alcohol and caffeine use may be both beneficial and detrimental, depending on quantity and frequency of use. Twin studies (including my own) demonstrated that both heritable and environmental factors play a role.
My proposal on substance use (nicotine, alcohol, cannabis and caffeine) is organized around several key objectives: 1. To unravel the complex contribution of genetic and environmental factors to substance use by using extended twin family designs; 2. To identify and confirm genes and gene networks involved in substance use by using DNA-variant data; 3. To explore gene expression patterns with RNA data in substance users versus non-users; 4. To investigate biomarkers in substance users versus non-users using blood or urine; 5. To unravel relation between substance use and health by linking twin-family data to national medical databases.
To realize these aims I will use the extensive resources of the Netherlands Twin Register (NTR); including both the longitudinal phenotype database and the biological samples. I have been involved in data collection, coordination of data collection and analyzing NTR data since 1999. With my comprehensive experience in data collection, data analyses and my knowledge in the field of behavior genetics and addiction research I will be able to successfully lead this cutting-edge project. Additional data crucial for the project will be collected by my team. Large samples will be available for this study and state-of-the art methods will be used to analyze the data. All together, my project will offer powerful approaches to unravel the complex interaction between genetic and environmental causes of individual differences in substance use and the risk for abuse.
Max ERC Funding
1 491 964 €
Duration
Start date: 2011-12-01, End date: 2017-05-31
Project acronym AdLibYeast
Project Synthetic platforms for ad libitum remodelling of yeast central metabolism
Researcher (PI) Pascale Andrée Simone Lapujade Daran
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Consolidator Grant (CoG), LS9, ERC-2014-CoG
Summary Replacement of petrochemistry by bio-based processes is key to sustainable development and requires microbes equipped with novel-to-nature capabilities. The efficiency of such engineered microbes strongly depends on their native metabolic networks. However, aeons of evolution have optimized these networks for fitness in nature rather than for industrial performance. As a result, central metabolic networks are complex and encoded by mosaic microbial genomes in which genes, irrespective of their function, are scattered over the genome and chromosomes. This absence of a modular organization tremendously restricts genetic accessibility and presents a major hurdle for fundamental understanding and rational engineering of central metabolism. To conquer this limitation, I introduce the concept of ‘pathway swapping’, which will enable experimenters to remodel the core machinery of microbes at will.
Using the yeast Saccharomyces cerevisiae, an industrial biotechnology work horse and model eukaryotic cell, I propose to design and construct a microbial chassis in which all genes encoding enzymes in central carbon metabolism are relocated to a specialized synthetic chromosome, from which they can be easily swapped by any – homologous or heterologous – synthetic pathway. This challenging and innovative project paves the way for a modular approach to engineering of central metabolism.
Beyond providing a ground-breaking enabling technology, the ultimate goal of the pathway swapping technology is to address hitherto unanswered fundamental questions. Access to a sheer endless variety of configurations of central metabolism offers unique, new possibilities to study the fundamental design of metabolic pathways, the constraints that have shaped them and unifying principles for their structure and regulation. Moreover, this technology enables fast, combinatorial optimization studies on central metabolism to optimize its performance in biotechnological purposes.
Summary
Replacement of petrochemistry by bio-based processes is key to sustainable development and requires microbes equipped with novel-to-nature capabilities. The efficiency of such engineered microbes strongly depends on their native metabolic networks. However, aeons of evolution have optimized these networks for fitness in nature rather than for industrial performance. As a result, central metabolic networks are complex and encoded by mosaic microbial genomes in which genes, irrespective of their function, are scattered over the genome and chromosomes. This absence of a modular organization tremendously restricts genetic accessibility and presents a major hurdle for fundamental understanding and rational engineering of central metabolism. To conquer this limitation, I introduce the concept of ‘pathway swapping’, which will enable experimenters to remodel the core machinery of microbes at will.
Using the yeast Saccharomyces cerevisiae, an industrial biotechnology work horse and model eukaryotic cell, I propose to design and construct a microbial chassis in which all genes encoding enzymes in central carbon metabolism are relocated to a specialized synthetic chromosome, from which they can be easily swapped by any – homologous or heterologous – synthetic pathway. This challenging and innovative project paves the way for a modular approach to engineering of central metabolism.
Beyond providing a ground-breaking enabling technology, the ultimate goal of the pathway swapping technology is to address hitherto unanswered fundamental questions. Access to a sheer endless variety of configurations of central metabolism offers unique, new possibilities to study the fundamental design of metabolic pathways, the constraints that have shaped them and unifying principles for their structure and regulation. Moreover, this technology enables fast, combinatorial optimization studies on central metabolism to optimize its performance in biotechnological purposes.
Max ERC Funding
2 149 718 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym ADULT
Project Analysis of the Dark Universe through Lensing Tomography
Researcher (PI) Hendrik Hoekstra
Host Institution (HI) UNIVERSITEIT LEIDEN
Call Details Starting Grant (StG), PE9, ERC-2011-StG_20101014
Summary The discoveries that the expansion of the universe is accelerating due to an unknown “dark energy”
and that most of the matter is invisible, highlight our lack of understanding of the major constituents
of the universe. These surprising findings set the stage for research in cosmology at the start of the
21st century. The objective of this proposal is to advance observational constraints to a level where we can distinguish between physical mechanisms that aim to explain the properties of dark energy and the observed distribution of dark matter throughout the universe. We use a relatively new technique called weak gravitational lensing: the accurate measurement of correlations in the orientations of distant galaxies enables us to map the dark matter distribution directly and to extract the cosmological information that is encoded by the large-scale structure.
To study the dark universe we will analyse data from a new state-of-the-art imaging survey: the Kilo-
Degree Survey (KiDS) will cover 1500 square degrees in 9 filters. The combination of its large survey
area and the availability of exquisite photometric redshifts for the sources makes KiDS the first
project that can place interesting constraints on the dark energy equation-of-state using lensing data
alone. Combined with complementary results from Planck, our measurements will provide one of the
best views of the dark side of the universe before much larger space-based projects commence.
To reach the desired accuracy we need to carefully measure the shapes of distant background galaxies. We also need to account for any intrinsic alignments that arise due to tidal interactions, rather than through lensing. Reducing these observational and physical biases to negligible levels is a necessarystep to ensure the success of KiDS and an important part of our preparation for more challenging projects such as the European-led space mission Euclid.
Summary
The discoveries that the expansion of the universe is accelerating due to an unknown “dark energy”
and that most of the matter is invisible, highlight our lack of understanding of the major constituents
of the universe. These surprising findings set the stage for research in cosmology at the start of the
21st century. The objective of this proposal is to advance observational constraints to a level where we can distinguish between physical mechanisms that aim to explain the properties of dark energy and the observed distribution of dark matter throughout the universe. We use a relatively new technique called weak gravitational lensing: the accurate measurement of correlations in the orientations of distant galaxies enables us to map the dark matter distribution directly and to extract the cosmological information that is encoded by the large-scale structure.
To study the dark universe we will analyse data from a new state-of-the-art imaging survey: the Kilo-
Degree Survey (KiDS) will cover 1500 square degrees in 9 filters. The combination of its large survey
area and the availability of exquisite photometric redshifts for the sources makes KiDS the first
project that can place interesting constraints on the dark energy equation-of-state using lensing data
alone. Combined with complementary results from Planck, our measurements will provide one of the
best views of the dark side of the universe before much larger space-based projects commence.
To reach the desired accuracy we need to carefully measure the shapes of distant background galaxies. We also need to account for any intrinsic alignments that arise due to tidal interactions, rather than through lensing. Reducing these observational and physical biases to negligible levels is a necessarystep to ensure the success of KiDS and an important part of our preparation for more challenging projects such as the European-led space mission Euclid.
Max ERC Funding
1 316 880 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym AFFORDS-HIGHER
Project Skilled Intentionality for 'Higher' Embodied Cognition: Joining forces with a field of affordances in flux
Researcher (PI) Dirk Willem Rietveld
Host Institution (HI) ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Call Details Starting Grant (StG), SH4, ERC-2015-STG
Summary In many situations experts act adequately, yet without deliberation. Architects e.g, immediately sense opportunities offered by the site of a new project. One could label these manifestations of expert intuition as ‘higher-level’ cognition, but still these experts act unreflectively. The aim of my project is to develop the Skilled Intentionality Framework (SIF), a new conceptual framework for the field of embodied/enactive cognitive science (Chemero, 2009; Thompson, 2007). I argue that affordances - possibilities for action provided by our surroundings - are highly significant in cases of unreflective and reflective ‘higher’ cognition. Skilled Intentionality is skilled coordination with multiple affordances simultaneously.
The two central ideas behind this proposal are (a) that episodes of skilled ‘higher’ cognition can be understood as responsiveness to affordances for ‘higher’ cognition and (b) that our surroundings are highly resourceful and contribute to skillful action and cognition in a far more fundamental way than is generally acknowledged. I use embedded philosophical research in a particular practice of architecture to shed new light on the ways in which affordances for ‘higher’ cognition support creative imagination, anticipation, explicit planning and self-reflection.
The Skilled Intentionality Framework is groundbreaking in relating findings established at several complementary levels of analysis: philosophy/phenomenology, ecological psychology, affective science and neurodynamics.
Empirical findings thought to be exclusively valid for everyday unreflective action can now be used to explain skilled ‘higher’ cognition as well. Moreover, SIF brings both the context and the social back into cognitive science. I will show SIF’s relevance for Friston’s work on the anticipating brain, and apply it in the domain of architecture and public health. SIF will radically widen the scope of the increasingly influential field of embodied cognitive science.
Summary
In many situations experts act adequately, yet without deliberation. Architects e.g, immediately sense opportunities offered by the site of a new project. One could label these manifestations of expert intuition as ‘higher-level’ cognition, but still these experts act unreflectively. The aim of my project is to develop the Skilled Intentionality Framework (SIF), a new conceptual framework for the field of embodied/enactive cognitive science (Chemero, 2009; Thompson, 2007). I argue that affordances - possibilities for action provided by our surroundings - are highly significant in cases of unreflective and reflective ‘higher’ cognition. Skilled Intentionality is skilled coordination with multiple affordances simultaneously.
The two central ideas behind this proposal are (a) that episodes of skilled ‘higher’ cognition can be understood as responsiveness to affordances for ‘higher’ cognition and (b) that our surroundings are highly resourceful and contribute to skillful action and cognition in a far more fundamental way than is generally acknowledged. I use embedded philosophical research in a particular practice of architecture to shed new light on the ways in which affordances for ‘higher’ cognition support creative imagination, anticipation, explicit planning and self-reflection.
The Skilled Intentionality Framework is groundbreaking in relating findings established at several complementary levels of analysis: philosophy/phenomenology, ecological psychology, affective science and neurodynamics.
Empirical findings thought to be exclusively valid for everyday unreflective action can now be used to explain skilled ‘higher’ cognition as well. Moreover, SIF brings both the context and the social back into cognitive science. I will show SIF’s relevance for Friston’s work on the anticipating brain, and apply it in the domain of architecture and public health. SIF will radically widen the scope of the increasingly influential field of embodied cognitive science.
Max ERC Funding
1 499 850 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym AFMIDMOA
Project "Applying Fundamental Mathematics in Discrete Mathematics, Optimization, and Algorithmics"
Researcher (PI) Alexander Schrijver
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), PE1, ERC-2013-ADG
Summary "This proposal aims at strengthening the connections between more fundamentally oriented areas of mathematics like algebra, geometry, analysis, and topology, and the more applied oriented and more recently emerging disciplines of discrete mathematics, optimization, and algorithmics.
The overall goal of the project is to obtain, with methods from fundamental mathematics, new effective tools to unravel the complexity of structures like graphs, networks, codes, knots, polynomials, and tensors, and to get a grip on such complex structures by new efficient characterizations, sharper bounds, and faster algorithms.
In the last few years, there have been several new developments where methods from representation theory, invariant theory, algebraic geometry, measure theory, functional analysis, and topology found new applications in discrete mathematics and optimization, both theoretically and algorithmically. Among the typical application areas are networks, coding, routing, timetabling, statistical and quantum physics, and computer science.
The project focuses in particular on:
A. Understanding partition functions with invariant theory and algebraic geometry
B. Graph limits, regularity, Hilbert spaces, and low rank approximation of polynomials
C. Reducing complexity in optimization by exploiting symmetry with representation theory
D. Reducing complexity in discrete optimization by homotopy and cohomology
These research modules are interconnected by themes like symmetry, regularity, and complexity, and by common methods from algebra, analysis, geometry, and topology."
Summary
"This proposal aims at strengthening the connections between more fundamentally oriented areas of mathematics like algebra, geometry, analysis, and topology, and the more applied oriented and more recently emerging disciplines of discrete mathematics, optimization, and algorithmics.
The overall goal of the project is to obtain, with methods from fundamental mathematics, new effective tools to unravel the complexity of structures like graphs, networks, codes, knots, polynomials, and tensors, and to get a grip on such complex structures by new efficient characterizations, sharper bounds, and faster algorithms.
In the last few years, there have been several new developments where methods from representation theory, invariant theory, algebraic geometry, measure theory, functional analysis, and topology found new applications in discrete mathematics and optimization, both theoretically and algorithmically. Among the typical application areas are networks, coding, routing, timetabling, statistical and quantum physics, and computer science.
The project focuses in particular on:
A. Understanding partition functions with invariant theory and algebraic geometry
B. Graph limits, regularity, Hilbert spaces, and low rank approximation of polynomials
C. Reducing complexity in optimization by exploiting symmetry with representation theory
D. Reducing complexity in discrete optimization by homotopy and cohomology
These research modules are interconnected by themes like symmetry, regularity, and complexity, and by common methods from algebra, analysis, geometry, and topology."
Max ERC Funding
2 001 598 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym AGGLONANOCOAT
Project The interplay between agglomeration and coating of nanoparticles in the gas phase
Researcher (PI) Jan Rudolf Van Ommen
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Starting Grant (StG), PE8, ERC-2011-StG_20101014
Summary This proposal aims to develop a generic synthesis approach for core-shell nanoparticles by unravelling the relevant mechanisms. Core-shell nanoparticles have high potential in heterogeneous catalysis, energy storage, and medical applications. However, on a fundamental level there is currently a poor understanding of how to produce such nanostructured particles in a controllable and scalable manner.
The main barriers to achieving this goal are understanding how nanoparticles agglomerate to loose dynamic clusters and controlling the agglomeration process in gas flows during coating, such that uniform coatings can be made. This is very challenging because of the two-way coupling between agglomeration and coating. During the coating we change the particle surfaces and thus the way the particles stick together. Correspondingly, the stickiness of particles determines how easy reactants can reach the surface.
Innovatively the project will be the first systematic study into this multi-scale phenomenon with investigations at all relevant length scales. Current synthesis approaches – mostly carried out in the liquid phase – are typically developed case by case. I will coat nanoparticles in the gas phase with atomic layer deposition (ALD): a technique from the semi-conductor industry that can deposit a wide range of materials. ALD applied to flat substrates offers excellent control over layer thickness. I will investigate the modification of single particle surfaces, particle-particle interaction, the structure of agglomerates, and the flow behaviour of large number of agglomerates. To this end, I will apply a multidisciplinary approach, combining disciplines as physical chemistry, fluid dynamics, and reaction engineering.
Summary
This proposal aims to develop a generic synthesis approach for core-shell nanoparticles by unravelling the relevant mechanisms. Core-shell nanoparticles have high potential in heterogeneous catalysis, energy storage, and medical applications. However, on a fundamental level there is currently a poor understanding of how to produce such nanostructured particles in a controllable and scalable manner.
The main barriers to achieving this goal are understanding how nanoparticles agglomerate to loose dynamic clusters and controlling the agglomeration process in gas flows during coating, such that uniform coatings can be made. This is very challenging because of the two-way coupling between agglomeration and coating. During the coating we change the particle surfaces and thus the way the particles stick together. Correspondingly, the stickiness of particles determines how easy reactants can reach the surface.
Innovatively the project will be the first systematic study into this multi-scale phenomenon with investigations at all relevant length scales. Current synthesis approaches – mostly carried out in the liquid phase – are typically developed case by case. I will coat nanoparticles in the gas phase with atomic layer deposition (ALD): a technique from the semi-conductor industry that can deposit a wide range of materials. ALD applied to flat substrates offers excellent control over layer thickness. I will investigate the modification of single particle surfaces, particle-particle interaction, the structure of agglomerates, and the flow behaviour of large number of agglomerates. To this end, I will apply a multidisciplinary approach, combining disciplines as physical chemistry, fluid dynamics, and reaction engineering.
Max ERC Funding
1 409 952 €
Duration
Start date: 2011-12-01, End date: 2016-11-30
Project acronym aidsocpro
Project Aiding Social Protection: the political economy of externally financing social policy in developing countries
Researcher (PI) Andrew Martin Fischer
Host Institution (HI) ERASMUS UNIVERSITEIT ROTTERDAM
Call Details Starting Grant (StG), SH2, ERC-2014-STG
Summary This research proposal explores the political economy of international development assistance (aid) directed towards social expenditures, examined through the lens of a particular financial quandary that has been ignored in the literature despite having important economic and political repercussions. The quandary is that aid cannot be directly spent on expenditures denominated in domestic currency. Instead, aid needs to be first converted into domestic currency whereas the foreign exchange provided is used for other purposes, resulting in a process prone to complex politics regarding domestic monetary policy and spending commitments.
The implications require a serious rethink of many of the accepted premises in the political economy of aid and related literatures.
It is urgent to engage in this rethinking given tensions between two dynamics in the current global political economy: a tightening financial cycle facing developing countries versus an increasing emphasis in international development agendas of directing aid towards social expenditures. The financial quandary might exacerbate these tensions, restricting recipient government policy space despite donor commitments of respecting national ownership.
The proposed research examines these implications through the emerging social protection agenda among donors, which serves as an ideal policy case given that social protection expenditures are almost entirely based on domestic currency. This will be researched through a mixed-method comparative case study of six developing countries, combining quantitative analysis of balance of payments and financing constraints with qualitative process tracing based on elite interviews and documentary research. The objective is to re-orient our thinking on these issues for a deeper appreciation of the systemic political and economic challenges facing global redistribution towards poorer countries, particularly with respect to the forthcoming Sustainable Development Goals.
Summary
This research proposal explores the political economy of international development assistance (aid) directed towards social expenditures, examined through the lens of a particular financial quandary that has been ignored in the literature despite having important economic and political repercussions. The quandary is that aid cannot be directly spent on expenditures denominated in domestic currency. Instead, aid needs to be first converted into domestic currency whereas the foreign exchange provided is used for other purposes, resulting in a process prone to complex politics regarding domestic monetary policy and spending commitments.
The implications require a serious rethink of many of the accepted premises in the political economy of aid and related literatures.
It is urgent to engage in this rethinking given tensions between two dynamics in the current global political economy: a tightening financial cycle facing developing countries versus an increasing emphasis in international development agendas of directing aid towards social expenditures. The financial quandary might exacerbate these tensions, restricting recipient government policy space despite donor commitments of respecting national ownership.
The proposed research examines these implications through the emerging social protection agenda among donors, which serves as an ideal policy case given that social protection expenditures are almost entirely based on domestic currency. This will be researched through a mixed-method comparative case study of six developing countries, combining quantitative analysis of balance of payments and financing constraints with qualitative process tracing based on elite interviews and documentary research. The objective is to re-orient our thinking on these issues for a deeper appreciation of the systemic political and economic challenges facing global redistribution towards poorer countries, particularly with respect to the forthcoming Sustainable Development Goals.
Max ERC Funding
1 459 529 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym AIDSRIGHTS
Project "Rights, Responsibilities, and the HIV/AIDS Pandemic: Global Impact on Moral and Political Subjectivity"
Researcher (PI) Jarrett Zigon
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Starting Grant (StG), SH2, ERC-2011-StG_20101124
Summary "This project will undertake a transnational, multi-sited ethnographic study of moral and political subjectivity in HIV/AIDS prevention and treatment programs from the perspective of socio-cultural anthropology. The main research question is: what kinds of politico-moral persons are constituted in institutional contexts that combine human rights and personal responsibility approaches to health, and how these kinds of subjectivities relate to local, national, and global forms of the politico-moral represented in health policies? In particular, this research will be carried out in Indonesia (Jakarta and Bali), South Africa (Western Cape), USA (New York City), and various locations throughout Eastern Europe in HIV/AIDS programs and institutions that increasingly combine human rights and personal responsibility approaches to treatment and prevention. This project is the first anthropological research on health governance done on a global scale. Until now most anthropological studies have focused on one health program in one location without simultaneously studying similar processes in comparable contexts in other parts of the world. In contrast, this project will take a global perspective on the relationship between health issues, morality, and governance by doing transnational multi-sited research. This project will significantly contribute to the current anthropological focus on bio-citizenship and push it in new directions, resulting in a new anthropological theory of global bio-political governance and global politico-moral subjectivities. This theory will describe and explain recent transnational processes of shaping particular kinds of politico-moral subjectivities through health initiatives. By doing research in comparable world areas this project will significantly contribute to the development of a theory of politico-moral governance with global reach."
Summary
"This project will undertake a transnational, multi-sited ethnographic study of moral and political subjectivity in HIV/AIDS prevention and treatment programs from the perspective of socio-cultural anthropology. The main research question is: what kinds of politico-moral persons are constituted in institutional contexts that combine human rights and personal responsibility approaches to health, and how these kinds of subjectivities relate to local, national, and global forms of the politico-moral represented in health policies? In particular, this research will be carried out in Indonesia (Jakarta and Bali), South Africa (Western Cape), USA (New York City), and various locations throughout Eastern Europe in HIV/AIDS programs and institutions that increasingly combine human rights and personal responsibility approaches to treatment and prevention. This project is the first anthropological research on health governance done on a global scale. Until now most anthropological studies have focused on one health program in one location without simultaneously studying similar processes in comparable contexts in other parts of the world. In contrast, this project will take a global perspective on the relationship between health issues, morality, and governance by doing transnational multi-sited research. This project will significantly contribute to the current anthropological focus on bio-citizenship and push it in new directions, resulting in a new anthropological theory of global bio-political governance and global politico-moral subjectivities. This theory will describe and explain recent transnational processes of shaping particular kinds of politico-moral subjectivities through health initiatives. By doing research in comparable world areas this project will significantly contribute to the development of a theory of politico-moral governance with global reach."
Max ERC Funding
1 499 370 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym AIM
Project Adaptive Imaging Microscopy
Researcher (PI) Michel Verhaegen
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Proof of Concept (PoC), PC1, ERC-2016-PoC
Summary The project has a goal of starting up a small business producing highly special customizable microscope systems for biomedical research. Microscopic imaging is one of the major drivers of the progress in biomedical and life sciences. The development of novel concepts, addressing the challenges of advanced optical microscopy, represents the front line of scientific research. Modern microscopes are not purely optical devices anymore. They have developed into complex integrated systems, combining optics, mechanics, electronics, feedback control systems, and image processing Many novel concepts of modern microscopy, while very interesting for research, still have to prove the commercial profitability. Such developments can be effectively addressed by start-up companies with a goal of either custom development, production and service of these advanced systems, or development and selling the IP to a larger player.
The major goal of this proposal is the creation of the first commercial optical microscope, the performance of which depends completely on the adaptive optics feedback controls. To prove the feasibility of this approach, we select a highly attractive technical concept of adaptive light sheet microscope, developed in our group in the framework of the ERC project. In this aspect, our development relates to ordinary microscope system in the same way as “fly by wire” airplane relates to an old-fashioned one.
Our contribution in the development of instrumentation for biomedical research will bring a positive impact on our knowledge about the nature and ourselves, the quality of life and life expectation of the population. Our proposal addresses the largest societal challenge of Europe: the healthcare. Our instrument will contribute to the understanding of complex diseases and support the greying population to stay healthy and self-supportive for extended period of time.
Summary
The project has a goal of starting up a small business producing highly special customizable microscope systems for biomedical research. Microscopic imaging is one of the major drivers of the progress in biomedical and life sciences. The development of novel concepts, addressing the challenges of advanced optical microscopy, represents the front line of scientific research. Modern microscopes are not purely optical devices anymore. They have developed into complex integrated systems, combining optics, mechanics, electronics, feedback control systems, and image processing Many novel concepts of modern microscopy, while very interesting for research, still have to prove the commercial profitability. Such developments can be effectively addressed by start-up companies with a goal of either custom development, production and service of these advanced systems, or development and selling the IP to a larger player.
The major goal of this proposal is the creation of the first commercial optical microscope, the performance of which depends completely on the adaptive optics feedback controls. To prove the feasibility of this approach, we select a highly attractive technical concept of adaptive light sheet microscope, developed in our group in the framework of the ERC project. In this aspect, our development relates to ordinary microscope system in the same way as “fly by wire” airplane relates to an old-fashioned one.
Our contribution in the development of instrumentation for biomedical research will bring a positive impact on our knowledge about the nature and ourselves, the quality of life and life expectation of the population. Our proposal addresses the largest societal challenge of Europe: the healthcare. Our instrument will contribute to the understanding of complex diseases and support the greying population to stay healthy and self-supportive for extended period of time.
Max ERC Funding
149 998 €
Duration
Start date: 2017-05-01, End date: 2018-10-31
Project acronym ALDof 2DTMDs
Project Atomic layer deposition of two-dimensional transition metal dichalcogenide nanolayers
Researcher (PI) Ageeth Bol
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Call Details Consolidator Grant (CoG), PE5, ERC-2014-CoG
Summary Two-dimensional transition metal dichalcogenides (2D-TMDs) are an exciting class of new materials. Their ultrathin body, optical band gap and unusual spin and valley polarization physics make them very promising candidates for a vast new range of (opto-)electronic applications. So far, most experimental work on 2D-TMDs has been performed on exfoliated flakes made by the ‘Scotch tape’ technique. The major next challenge is the large-area synthesis of 2D-TMDs by a technique that ultimately can be used for commercial device fabrication.
Building upon pure 2D-TMDs, even more functionalities can be gained from 2D-TMD alloys and heterostructures. Theoretical work on these derivates reveals exciting new phenomena, but experimentally this field is largely unexplored due to synthesis technique limitations.
The goal of this proposal is to combine atomic layer deposition with plasma chemistry to create a novel surface-controlled, industry-compatible synthesis technique that will make large area 2D-TMDs, 2D-TMD alloys and 2D-TMD heterostructures a reality. This innovative approach will enable systematic layer dependent studies, likely revealing exciting new properties, and provide integration pathways for a multitude of applications.
Atomistic simulations will guide the process development and, together with in- and ex-situ analysis, increase the understanding of the surface chemistry involved. State-of-the-art high resolution transmission electron microscopy will be used to study the alloying process and the formation of heterostructures. Luminescence spectroscopy and electrical characterization will reveal the potential of the synthesized materials for (opto)-electronic applications.
The synergy between the excellent background of the PI in 2D materials for nanoelectronics and the group’s leading expertise in ALD and plasma science is unique and provides an ideal stepping stone to develop the synthesis of large-area 2D-TMDs and derivatives.
Summary
Two-dimensional transition metal dichalcogenides (2D-TMDs) are an exciting class of new materials. Their ultrathin body, optical band gap and unusual spin and valley polarization physics make them very promising candidates for a vast new range of (opto-)electronic applications. So far, most experimental work on 2D-TMDs has been performed on exfoliated flakes made by the ‘Scotch tape’ technique. The major next challenge is the large-area synthesis of 2D-TMDs by a technique that ultimately can be used for commercial device fabrication.
Building upon pure 2D-TMDs, even more functionalities can be gained from 2D-TMD alloys and heterostructures. Theoretical work on these derivates reveals exciting new phenomena, but experimentally this field is largely unexplored due to synthesis technique limitations.
The goal of this proposal is to combine atomic layer deposition with plasma chemistry to create a novel surface-controlled, industry-compatible synthesis technique that will make large area 2D-TMDs, 2D-TMD alloys and 2D-TMD heterostructures a reality. This innovative approach will enable systematic layer dependent studies, likely revealing exciting new properties, and provide integration pathways for a multitude of applications.
Atomistic simulations will guide the process development and, together with in- and ex-situ analysis, increase the understanding of the surface chemistry involved. State-of-the-art high resolution transmission electron microscopy will be used to study the alloying process and the formation of heterostructures. Luminescence spectroscopy and electrical characterization will reveal the potential of the synthesized materials for (opto)-electronic applications.
The synergy between the excellent background of the PI in 2D materials for nanoelectronics and the group’s leading expertise in ALD and plasma science is unique and provides an ideal stepping stone to develop the synthesis of large-area 2D-TMDs and derivatives.
Max ERC Funding
1 968 709 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym ALERT
Project ALERT - The Apertif-LOFAR Exploration of the Radio Transient Sky
Researcher (PI) Albert Van Leeuwen
Host Institution (HI) STICHTING ASTRON, NETHERLANDS INSTITUTE FOR RADIO ASTRONOMY
Call Details Consolidator Grant (CoG), PE9, ERC-2013-CoG
Summary "In our largely unchanging radio Universe, a highly dynamic component was recently discovered: flashes of bright radio emission that last only milliseconds but appear all over the sky. Some of these radio bursts can be traced to intermittently pulsating neutron stars. Other bursts however, apparently originate far outside our Galaxy. Due to great observational challenges, the evolution of the neutron stars is not understood, while more importantly, the nature of the extragalactic bursts remains an outright mystery.
My overall aim is to understand the physics that drives both kinds of brief and luminous bursts.
My primary goal is to identify the highly compact astrophysical explosions powering the extragalactic bursts. My previous surveys are the state of the art in fast-transient detection; I will now increase by a factor of 10 this exploration volume. In real-time I will provide arcsec positions, 10,000-fold more accurate than currently possible, to localize such extragalactic bursts for the first time and understand their origin.
My secondary goal is to unravel the unexplained evolution of intermittently pulsating neutron stars (building on e.g., my recent papers in Science, 2013), by doubling their number and modeling their population.
To achieve these goals, I will carry out a highly innovative survey: the Apertif-LOFAR Exploration of the Radio Transient Sky. ALERT is over an order of magnitude more sensitive than all current state-of-the art fast-transient surveys.
Through its novel, extremely wide field-of-view, Westerbork/Apertif will detect many tens of extragalactic bursts. Through real-time triggers to LOFAR I will next provide the precise localisation that is essential for radio, optical and high-energy follow-up to, for the first time, shed light on the physics and objects driving these bursts – evaporating primordial black holes; explosions in host galaxies; or, the unknown?"
Summary
"In our largely unchanging radio Universe, a highly dynamic component was recently discovered: flashes of bright radio emission that last only milliseconds but appear all over the sky. Some of these radio bursts can be traced to intermittently pulsating neutron stars. Other bursts however, apparently originate far outside our Galaxy. Due to great observational challenges, the evolution of the neutron stars is not understood, while more importantly, the nature of the extragalactic bursts remains an outright mystery.
My overall aim is to understand the physics that drives both kinds of brief and luminous bursts.
My primary goal is to identify the highly compact astrophysical explosions powering the extragalactic bursts. My previous surveys are the state of the art in fast-transient detection; I will now increase by a factor of 10 this exploration volume. In real-time I will provide arcsec positions, 10,000-fold more accurate than currently possible, to localize such extragalactic bursts for the first time and understand their origin.
My secondary goal is to unravel the unexplained evolution of intermittently pulsating neutron stars (building on e.g., my recent papers in Science, 2013), by doubling their number and modeling their population.
To achieve these goals, I will carry out a highly innovative survey: the Apertif-LOFAR Exploration of the Radio Transient Sky. ALERT is over an order of magnitude more sensitive than all current state-of-the art fast-transient surveys.
Through its novel, extremely wide field-of-view, Westerbork/Apertif will detect many tens of extragalactic bursts. Through real-time triggers to LOFAR I will next provide the precise localisation that is essential for radio, optical and high-energy follow-up to, for the first time, shed light on the physics and objects driving these bursts – evaporating primordial black holes; explosions in host galaxies; or, the unknown?"
Max ERC Funding
1 999 823 €
Duration
Start date: 2014-12-01, End date: 2019-11-30
Project acronym ALEX
Project ALgorithms EXposed. Investigating Automated Personalization and Filtering for Research and Activism
Researcher (PI) Stefania MILAN
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary Personalization algorithms—filtering content on the basis of someone's profile—increasingly mediate the web experience of users. By forging a specific reality for each individual, they silently shape customized 'information diets': in other words, they determine which news, opinions and rumors users are exposed to. Restricting users’ possibilities, they ultimately infringe on their agency. As exposed by the recent Cambridge Analytica scandal, they are supported by questionable data sharing practices at the core of the business models of the social media industry. Yet, personalization algorithms are proprietary and thus remain inaccessible to end users. The few experiments auditing these algorithms rely on data provided by platform companies themselves. They are highly technical, hardly scalable, and fail to put social media users in the driver seat. The ALgorithms EXposed (ALEX) project aims at unmasking the functioning of personalization algorithms on social media platforms, taking Facebook as a test case. It is 'data activism' in practice, as it uses publicly available data for awareness raising and citizen empowerment. ALEX will pursue five goals: 1) software development and stabilization, building on the alpha version of facebook.tracking.exposed (fbtrex), a working prototype of a browser extension analyzing the outcomes of Facebook's News Feed algorithms; 2) the release of two spin-off products building on fbtrex, namely AudIT, enabling researchers to do expert analysis on algorithmic biases, and RealityCheck, allowing users to monitor their own social media consumption patterns; 3) testing the technical feasibility of adapting the ALEX approach to analyze algorithmic personalization on other platforms such as Twitter and Google; 4) the design and organization of data literacy modules on algorithmic personalization, and 5) the launch of a consultancy service to promote tool take-up and the future sustainability of the project.
Summary
Personalization algorithms—filtering content on the basis of someone's profile—increasingly mediate the web experience of users. By forging a specific reality for each individual, they silently shape customized 'information diets': in other words, they determine which news, opinions and rumors users are exposed to. Restricting users’ possibilities, they ultimately infringe on their agency. As exposed by the recent Cambridge Analytica scandal, they are supported by questionable data sharing practices at the core of the business models of the social media industry. Yet, personalization algorithms are proprietary and thus remain inaccessible to end users. The few experiments auditing these algorithms rely on data provided by platform companies themselves. They are highly technical, hardly scalable, and fail to put social media users in the driver seat. The ALgorithms EXposed (ALEX) project aims at unmasking the functioning of personalization algorithms on social media platforms, taking Facebook as a test case. It is 'data activism' in practice, as it uses publicly available data for awareness raising and citizen empowerment. ALEX will pursue five goals: 1) software development and stabilization, building on the alpha version of facebook.tracking.exposed (fbtrex), a working prototype of a browser extension analyzing the outcomes of Facebook's News Feed algorithms; 2) the release of two spin-off products building on fbtrex, namely AudIT, enabling researchers to do expert analysis on algorithmic biases, and RealityCheck, allowing users to monitor their own social media consumption patterns; 3) testing the technical feasibility of adapting the ALEX approach to analyze algorithmic personalization on other platforms such as Twitter and Google; 4) the design and organization of data literacy modules on algorithmic personalization, and 5) the launch of a consultancy service to promote tool take-up and the future sustainability of the project.
Max ERC Funding
149 922 €
Duration
Start date: 2018-12-01, End date: 2020-02-29
Project acronym ALGSTRONGCRYPTO
Project Algebraic Methods for Stronger Crypto
Researcher (PI) Ronald John Fitzgerald CRAMER
Host Institution (HI) STICHTING NEDERLANDSE WETENSCHAPPELIJK ONDERZOEK INSTITUTEN
Call Details Advanced Grant (AdG), PE6, ERC-2016-ADG
Summary Our field is cryptology. Our overarching objective is to advance significantly the frontiers in
design and analysis of high-security cryptography for the future generation.
Particularly, we wish to enhance the efficiency, functionality, and, last-but-not-least, fundamental understanding of cryptographic security against very powerful adversaries.
Our approach here is to develop completely novel methods by
deepening, strengthening and broadening the
algebraic foundations of the field.
Concretely, our lens builds on
the arithmetic codex. This is a general, abstract cryptographic primitive whose basic theory we recently developed and whose asymptotic part, which relies on algebraic geometry, enjoys crucial applications in surprising foundational results on constant communication-rate two-party cryptography. A codex is a linear (error correcting) code that, when endowing its ambient vector space just with coordinate-wise multiplication, can be viewed as simulating, up to some degree, richer arithmetical structures such as finite fields (or products thereof), or generally, finite-dimensional algebras over finite fields. Besides this degree, coordinate-localities for which simulation holds and for which it does not at all are also captured.
Our method is based on novel perspectives on codices which significantly
widen their scope and strengthen their utility. Particularly, we bring
symmetries, computational- and complexity theoretic aspects, and connections with algebraic number theory, -geometry, and -combinatorics into play in novel ways. Our applications range from public-key cryptography to secure multi-party computation.
Our proposal is subdivided into 3 interconnected modules:
(1) Algebraic- and Number Theoretical Cryptanalysis
(2) Construction of Algebraic Crypto Primitives
(3) Advanced Theory of Arithmetic Codices
Summary
Our field is cryptology. Our overarching objective is to advance significantly the frontiers in
design and analysis of high-security cryptography for the future generation.
Particularly, we wish to enhance the efficiency, functionality, and, last-but-not-least, fundamental understanding of cryptographic security against very powerful adversaries.
Our approach here is to develop completely novel methods by
deepening, strengthening and broadening the
algebraic foundations of the field.
Concretely, our lens builds on
the arithmetic codex. This is a general, abstract cryptographic primitive whose basic theory we recently developed and whose asymptotic part, which relies on algebraic geometry, enjoys crucial applications in surprising foundational results on constant communication-rate two-party cryptography. A codex is a linear (error correcting) code that, when endowing its ambient vector space just with coordinate-wise multiplication, can be viewed as simulating, up to some degree, richer arithmetical structures such as finite fields (or products thereof), or generally, finite-dimensional algebras over finite fields. Besides this degree, coordinate-localities for which simulation holds and for which it does not at all are also captured.
Our method is based on novel perspectives on codices which significantly
widen their scope and strengthen their utility. Particularly, we bring
symmetries, computational- and complexity theoretic aspects, and connections with algebraic number theory, -geometry, and -combinatorics into play in novel ways. Our applications range from public-key cryptography to secure multi-party computation.
Our proposal is subdivided into 3 interconnected modules:
(1) Algebraic- and Number Theoretical Cryptanalysis
(2) Construction of Algebraic Crypto Primitives
(3) Advanced Theory of Arithmetic Codices
Max ERC Funding
2 447 439 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym ALLEGRO
Project unrAvelLing sLow modE travelinG and tRaffic: with innOvative data to a new transportation and traffic theory for pedestrians and bicycles
Researcher (PI) Serge Hoogendoorn
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Advanced Grant (AdG), SH3, ERC-2014-ADG
Summary A major challenge in contemporary traffic and transportation theory is having a comprehensive understanding of pedestrians and cyclists behaviour. This is notoriously hard to observe, since sensors providing abundant and detailed information about key variables characterising this behaviour have not been available until very recently. The behaviour is also far more complex than that of the much better understood fast mode. This is due to the many degrees of freedom in decision-making, the interactions among slow traffic participants that are more involved and far less guided by traffic rules and regulations than those between car-drivers, and the many fascinating but complex phenomena in slow traffic flows (self-organised patterns, turbulence, spontaneous phase transitions, herding, etc.) that are very hard to predict accurately.
With slow traffic modes gaining ground in terms of mode share in many cities, lack of empirical insights, behavioural theories, predictively valid analytical and simulation models, and tools to support planning, design, management and control is posing a major societal problem as well: examples of major accidents due to bad planning, organisation and management of events are manifold, as are locations where safety of slow modes is a serious issue due to interactions with fast modes.
This programme is geared towards establishing a comprehensive theory of slow mode traffic behaviour, considering the different behavioural levels relevant for understanding, reproducing and predicting slow mode traffic flows in cities. The levels deal with walking and cycling operations, activity scheduling and travel behaviour, and knowledge representation and learning. Major scientific breakthroughs are expected at each of these levels, in terms of theory and modelling, by using innovative (big) data collection and experimentation, analysis and fusion techniques, including social media data analytics, using augmented reality, and remote and crowd sensing.
Summary
A major challenge in contemporary traffic and transportation theory is having a comprehensive understanding of pedestrians and cyclists behaviour. This is notoriously hard to observe, since sensors providing abundant and detailed information about key variables characterising this behaviour have not been available until very recently. The behaviour is also far more complex than that of the much better understood fast mode. This is due to the many degrees of freedom in decision-making, the interactions among slow traffic participants that are more involved and far less guided by traffic rules and regulations than those between car-drivers, and the many fascinating but complex phenomena in slow traffic flows (self-organised patterns, turbulence, spontaneous phase transitions, herding, etc.) that are very hard to predict accurately.
With slow traffic modes gaining ground in terms of mode share in many cities, lack of empirical insights, behavioural theories, predictively valid analytical and simulation models, and tools to support planning, design, management and control is posing a major societal problem as well: examples of major accidents due to bad planning, organisation and management of events are manifold, as are locations where safety of slow modes is a serious issue due to interactions with fast modes.
This programme is geared towards establishing a comprehensive theory of slow mode traffic behaviour, considering the different behavioural levels relevant for understanding, reproducing and predicting slow mode traffic flows in cities. The levels deal with walking and cycling operations, activity scheduling and travel behaviour, and knowledge representation and learning. Major scientific breakthroughs are expected at each of these levels, in terms of theory and modelling, by using innovative (big) data collection and experimentation, analysis and fusion techniques, including social media data analytics, using augmented reality, and remote and crowd sensing.
Max ERC Funding
2 458 700 €
Duration
Start date: 2015-11-01, End date: 2020-10-31
Project acronym ALMP_ECON
Project Effective evaluation of active labour market policies in social insurance programs - improving the interaction between econometric evaluation estimators and economic theory
Researcher (PI) Bas Van Der Klaauw
Host Institution (HI) STICHTING VU
Call Details Starting Grant (StG), SH1, ERC-2007-StG
Summary In most European countries social insurance programs, like welfare, unemployment insurance and disability insurance are characterized by low reemployment rates. Therefore, governments spend huge amounts of money on active labour market programs, which should help individuals in finding work. Recent surveys indicate that programs which aim at intensifying job search behaviour are much more effective than schooling programs for improving human capital. A second conclusion from these surveys is that despite the size of the spendings on these programs, evidence on its effectiveness is limited. This research proposal aims at developing an economic framework that will be used to evaluate the effectiveness of popular programs like offering reemployment bonuses, fraud detection, workfare and job search monitoring. The main innovation is that I will combine economic theory with recently developed econometric techniques and detailed administrative data sets, which have not been explored before. While most of the literature only focuses on short-term outcomes, the available data allow me to also consider the long-term effectiveness of programs. The key advantage of an economic model is that I can compare the effectiveness of the different programs, consider modifications of programs and combinations of programs. Furthermore, using an economic model I can construct profiling measures to improve the targeting of programs to subsamples of the population. This is particularly relevant if the effectiveness of programs differs between individuals or depends on the moment in time the program is offered. Therefore, the results from this research will not only be of scientific interest, but will also be of great value to policymakers.
Summary
In most European countries social insurance programs, like welfare, unemployment insurance and disability insurance are characterized by low reemployment rates. Therefore, governments spend huge amounts of money on active labour market programs, which should help individuals in finding work. Recent surveys indicate that programs which aim at intensifying job search behaviour are much more effective than schooling programs for improving human capital. A second conclusion from these surveys is that despite the size of the spendings on these programs, evidence on its effectiveness is limited. This research proposal aims at developing an economic framework that will be used to evaluate the effectiveness of popular programs like offering reemployment bonuses, fraud detection, workfare and job search monitoring. The main innovation is that I will combine economic theory with recently developed econometric techniques and detailed administrative data sets, which have not been explored before. While most of the literature only focuses on short-term outcomes, the available data allow me to also consider the long-term effectiveness of programs. The key advantage of an economic model is that I can compare the effectiveness of the different programs, consider modifications of programs and combinations of programs. Furthermore, using an economic model I can construct profiling measures to improve the targeting of programs to subsamples of the population. This is particularly relevant if the effectiveness of programs differs between individuals or depends on the moment in time the program is offered. Therefore, the results from this research will not only be of scientific interest, but will also be of great value to policymakers.
Max ERC Funding
550 000 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
Project acronym ALPROS
Project Artificial Life-like Processive Systems
Researcher (PI) Roeland Johannes Maria Nolte
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), PE5, ERC-2011-ADG_20110209
Summary Toroidal processive enzymes (e.g. enzymes/proteins that are able to thread onto biopolymers and to perform stepwise reactions along the polymer chain) are among the most fascinating tools involved in the clockwork machinery of life. Processive catalysis is ubiquitous in Nature, viz. DNA polymerases, endo- and exo-nucleases and; it plays a crucial role in numerous events of the cell’s life, including most of the replication, transmission, and expression and repair processes of the genetic information. In the case of DNA polymerases the protein catalyst encircles the DNA and whilst moving along it, make copies of high fidelity. Although numerous works have been reported in relation with the synthesis of natural enzymes' analogues, very few efforts have been paid in comparison to mimic these processive properties. It is the goal of this proposal to rectify this oversight and unravel the essential components of Nature’s polymer catalysts. The individual projects are designed to specifically target the essential aspects of processive catalysis, i.e. rate of motion, rate of catalysis, and transfer of information. One project is aimed at extending the research into a processive catalytic system that is more suitable for industrial application. Two projects involve more farsighted studies and are designed to push the research way beyond the current boundaries into the area of Turing machines and bio-rotaxane catalysts which can modify DNA in a non-natural process. The vision of this proposal is to open up the field of ‘processive catalysis’ and invigorate the next generation of chemists to develop information transfer and toroidal processive catalysts. The construction of synthetic analogues of processive enzymes could open a gate toward a large range of applications, ranging from intelligent tailoring of polymers to information storage and processing.
Summary
Toroidal processive enzymes (e.g. enzymes/proteins that are able to thread onto biopolymers and to perform stepwise reactions along the polymer chain) are among the most fascinating tools involved in the clockwork machinery of life. Processive catalysis is ubiquitous in Nature, viz. DNA polymerases, endo- and exo-nucleases and; it plays a crucial role in numerous events of the cell’s life, including most of the replication, transmission, and expression and repair processes of the genetic information. In the case of DNA polymerases the protein catalyst encircles the DNA and whilst moving along it, make copies of high fidelity. Although numerous works have been reported in relation with the synthesis of natural enzymes' analogues, very few efforts have been paid in comparison to mimic these processive properties. It is the goal of this proposal to rectify this oversight and unravel the essential components of Nature’s polymer catalysts. The individual projects are designed to specifically target the essential aspects of processive catalysis, i.e. rate of motion, rate of catalysis, and transfer of information. One project is aimed at extending the research into a processive catalytic system that is more suitable for industrial application. Two projects involve more farsighted studies and are designed to push the research way beyond the current boundaries into the area of Turing machines and bio-rotaxane catalysts which can modify DNA in a non-natural process. The vision of this proposal is to open up the field of ‘processive catalysis’ and invigorate the next generation of chemists to develop information transfer and toroidal processive catalysts. The construction of synthetic analogues of processive enzymes could open a gate toward a large range of applications, ranging from intelligent tailoring of polymers to information storage and processing.
Max ERC Funding
1 603 699 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym AlterMateria
Project Designer Quantum Materials Out of Equilibrium
Researcher (PI) Andrea Caviglia
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Starting Grant (StG), PE3, ERC-2015-STG
Summary Recently, ‘designer’ quantum materials, synthesised layer by layer, have been realised, sparking ground-breaking new scientific insights. These artificial materials, such as oxide heterostructures, are interesting building blocks for a new generation of technologies, provided that one is able to access, study and ultimately control their quantum phases in practical conditions such as at room temperature and high speeds.
On the other hand, an independent research area is emerging that uses ultra-short bursts of light to stimulate changes in the macroscopic electronic properties of solids at unprecedented speeds.
Here I propose to bridge the gap between material design and ultrafast control of solids. This new synergy will allow us to explore fundamental research questions on the non-equilibrium dynamics of quantum materials with competing ground states. Specifically, I will utilize intense THz and mid-infrared electromagnetic fields to manipulate the electronic properties of artificial quantum materials on pico- to femto-second time scales. Beyond the development of novel techniques to generate THz electric fields of unprecedented intensity, I will investigate metal-insulator and magnetic transitions in oxide heterostructures as they unfold in time. This research programme takes oxide electronics in a new direction and establishes a new methodology for the control of quantum phases at high temperature and high speed.
Summary
Recently, ‘designer’ quantum materials, synthesised layer by layer, have been realised, sparking ground-breaking new scientific insights. These artificial materials, such as oxide heterostructures, are interesting building blocks for a new generation of technologies, provided that one is able to access, study and ultimately control their quantum phases in practical conditions such as at room temperature and high speeds.
On the other hand, an independent research area is emerging that uses ultra-short bursts of light to stimulate changes in the macroscopic electronic properties of solids at unprecedented speeds.
Here I propose to bridge the gap between material design and ultrafast control of solids. This new synergy will allow us to explore fundamental research questions on the non-equilibrium dynamics of quantum materials with competing ground states. Specifically, I will utilize intense THz and mid-infrared electromagnetic fields to manipulate the electronic properties of artificial quantum materials on pico- to femto-second time scales. Beyond the development of novel techniques to generate THz electric fields of unprecedented intensity, I will investigate metal-insulator and magnetic transitions in oxide heterostructures as they unfold in time. This research programme takes oxide electronics in a new direction and establishes a new methodology for the control of quantum phases at high temperature and high speed.
Max ERC Funding
1 499 982 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym ANAMMOX
Project Anaerobic ammonium oxidizing bacteria: unique prokayotes with exceptional properties
Researcher (PI) Michael Silvester Maria Jetten
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), LS8, ERC-2008-AdG
Summary For over a century it was believed that ammonium could only be oxidized by microbes in the presence of oxygen. The possibility of anaerobic ammonium oxidation (anammox) was considered impossible. However, about 10 years ago the microbes responsible for the anammox reaction were discovered in a wastewater plant. This was followed by the identification of the responsible bacteria. Recently, the widespread environmental occurrence of the anammox bacteria was demonstrated leading to the realization that anammox bacteria may play a major role in biological nitrogen cycling. The anammox bacteria are unique microbes with many unusual properties. These include the biological turn-over of hydrazine, a well known rocket fuel, the biological synthesis of ladderane lipids, and the presence of a prokaryotic organelle in the cytoplasma of anammox bacteria. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the anammox bacteria. Such understanding contributes directly to our environment and economy because the anammox bacteria form a new opportunity for nitrogen removal from wastewater, cheaper, with lower carbon dioxide emissions than existing technology. Scientifically the results will contribute to the understanding how hydrazine and dinitrogen gas are made by the anammox bacteria. The research will show which gene products are responsible for the anammox reaction, and how their expression is regulated. Furthermore, the experiments proposed will show if the prokaryotic organelle in anammox bacteria is involved in energy generation. Together the environmental and metabolic data will help to understand why anammox bacteria are so successful in the biogeochemical nitrogen cycle and thus shape our planets atmosphere. The different research lines will employ state of the art microbial and molecular methods to unravel the exceptional properties of these highly unusual and important anammox bacteria.
Summary
For over a century it was believed that ammonium could only be oxidized by microbes in the presence of oxygen. The possibility of anaerobic ammonium oxidation (anammox) was considered impossible. However, about 10 years ago the microbes responsible for the anammox reaction were discovered in a wastewater plant. This was followed by the identification of the responsible bacteria. Recently, the widespread environmental occurrence of the anammox bacteria was demonstrated leading to the realization that anammox bacteria may play a major role in biological nitrogen cycling. The anammox bacteria are unique microbes with many unusual properties. These include the biological turn-over of hydrazine, a well known rocket fuel, the biological synthesis of ladderane lipids, and the presence of a prokaryotic organelle in the cytoplasma of anammox bacteria. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the anammox bacteria. Such understanding contributes directly to our environment and economy because the anammox bacteria form a new opportunity for nitrogen removal from wastewater, cheaper, with lower carbon dioxide emissions than existing technology. Scientifically the results will contribute to the understanding how hydrazine and dinitrogen gas are made by the anammox bacteria. The research will show which gene products are responsible for the anammox reaction, and how their expression is regulated. Furthermore, the experiments proposed will show if the prokaryotic organelle in anammox bacteria is involved in energy generation. Together the environmental and metabolic data will help to understand why anammox bacteria are so successful in the biogeochemical nitrogen cycle and thus shape our planets atmosphere. The different research lines will employ state of the art microbial and molecular methods to unravel the exceptional properties of these highly unusual and important anammox bacteria.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym AncientAdhesives
Project Ancient Adhesives - A window on prehistoric technological complexity
Researcher (PI) Geeske LANGEJANS
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Starting Grant (StG), SH6, ERC-2018-STG
Summary AncientAdhesives addresses the most crucial problem in Palaeolithic archaeology: How to reliably infer cognitively complex behaviour in the deep past. To study the evolution of Neandertal and modern human cognitive capacities, certain find categories are taken to reflect behavioural and thus cognitive complexitye.g. Among these are art objects, personal ornaments and complex technology. Of these technology is best-suited to trace changing behavioural complexity, because 1) it is the least vulnerable to differential preservation, and 2) technological behaviours are present throughout the history of our genus. Adhesives are the oldest examples of highly complex technology. They are also known earlier from Neandertal than from modern human contexts. Understanding their technological complexity is thus essential to resolve debates on differences in cognitive complexity of both species. However, currently, there is no agreed-upon method to measure technological complexity.
The aim of AncientAdhesives is to create the first reliable method to compare the complexity of Neandertal and modern human technologies. This is achieved through three main objectives:
1. Collate the first comprehensive body of knowledge on adhesives, including ethnography, archaeology and (experimental) material properties (e.g. preservation, production).
2. Develop a new archaeological methodology by modifying industrial process modelling for archaeological applications.
3. Evaluate the development of adhesive technological complexity through time and across species using a range of explicit complexity measures.
By analysing adhesives, it is possible to measure technological complexity, to identify idiosyncratic behaviours and to track adoption and loss of complex technological know-how. This represents a step-change in debates about the development of behavioural complexity and differences/similarities between Neanderthals and modern humans.
Summary
AncientAdhesives addresses the most crucial problem in Palaeolithic archaeology: How to reliably infer cognitively complex behaviour in the deep past. To study the evolution of Neandertal and modern human cognitive capacities, certain find categories are taken to reflect behavioural and thus cognitive complexitye.g. Among these are art objects, personal ornaments and complex technology. Of these technology is best-suited to trace changing behavioural complexity, because 1) it is the least vulnerable to differential preservation, and 2) technological behaviours are present throughout the history of our genus. Adhesives are the oldest examples of highly complex technology. They are also known earlier from Neandertal than from modern human contexts. Understanding their technological complexity is thus essential to resolve debates on differences in cognitive complexity of both species. However, currently, there is no agreed-upon method to measure technological complexity.
The aim of AncientAdhesives is to create the first reliable method to compare the complexity of Neandertal and modern human technologies. This is achieved through three main objectives:
1. Collate the first comprehensive body of knowledge on adhesives, including ethnography, archaeology and (experimental) material properties (e.g. preservation, production).
2. Develop a new archaeological methodology by modifying industrial process modelling for archaeological applications.
3. Evaluate the development of adhesive technological complexity through time and across species using a range of explicit complexity measures.
By analysing adhesives, it is possible to measure technological complexity, to identify idiosyncratic behaviours and to track adoption and loss of complex technological know-how. This represents a step-change in debates about the development of behavioural complexity and differences/similarities between Neanderthals and modern humans.
Max ERC Funding
1 499 926 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym APOLOGY
Project Political Apologies across Cultures
Researcher (PI) Juliëtte Schaafsma
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT BRABANT
Call Details Consolidator Grant (CoG), SH2, ERC-2015-CoG
Summary In the past decades, there has been a considerable rise in the number of apologies offered by states for injustices and human rights violations. Among transitional justice scholars, there is significant debate about how useful such apologies are. Whereas some have applauded these gestures as an important step in peacemaking processes, others have argued that they may not fit in all cultures and may even be a risky tool for peacemaking. Unfortunately, theorizing and research in the field of transitional justice is still in its infancy and has not systematically addressed questions of cross-cultural variability yet. So, at present, we do not know whether political apologies are a universally viable way to restore justice and harmony. My project addresses this challenge. Using an innovative, interdisciplinary, and multi-method approach with in-depth interviews, (experimental) surveys, and content analyses of apologies, I analyze whether there are universals in how political apologies are valued, expressed, and interpreted or whether this varies as a function of cross-cultural differences in key values (collectivism and individualism) and norms (face and honor). Based on these findings, I build a theoretical framework that will fundamentally advance our understanding of the potential value and role of apologies in transitional justice processes. This project breaks new ground because it is the first to take the difficult step to collect cross-cultural data to examine whether key assumptions regarding political apologies hold across cultures. It is also the first in this area to use a multi-method approach, which makes it possible to take into account the complex reality of political apologies. Combining insights from transitional justice, cross-cultural psychology and anthropology, this project places theorizing on transitional justice on a much firmer footing and paves the way to more cross-culturally valid models to restore justice and promote reconciliation.
Summary
In the past decades, there has been a considerable rise in the number of apologies offered by states for injustices and human rights violations. Among transitional justice scholars, there is significant debate about how useful such apologies are. Whereas some have applauded these gestures as an important step in peacemaking processes, others have argued that they may not fit in all cultures and may even be a risky tool for peacemaking. Unfortunately, theorizing and research in the field of transitional justice is still in its infancy and has not systematically addressed questions of cross-cultural variability yet. So, at present, we do not know whether political apologies are a universally viable way to restore justice and harmony. My project addresses this challenge. Using an innovative, interdisciplinary, and multi-method approach with in-depth interviews, (experimental) surveys, and content analyses of apologies, I analyze whether there are universals in how political apologies are valued, expressed, and interpreted or whether this varies as a function of cross-cultural differences in key values (collectivism and individualism) and norms (face and honor). Based on these findings, I build a theoretical framework that will fundamentally advance our understanding of the potential value and role of apologies in transitional justice processes. This project breaks new ground because it is the first to take the difficult step to collect cross-cultural data to examine whether key assumptions regarding political apologies hold across cultures. It is also the first in this area to use a multi-method approach, which makes it possible to take into account the complex reality of political apologies. Combining insights from transitional justice, cross-cultural psychology and anthropology, this project places theorizing on transitional justice on a much firmer footing and paves the way to more cross-culturally valid models to restore justice and promote reconciliation.
Max ERC Funding
1 917 713 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym APPROAcH
Project APPROAcH: Antimicrobial and Save 3D-Printable Polymers for Oral Health
Researcher (PI) Andreas Herrmann
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Proof of Concept (PoC), PC1, ERC-2014-PoC
Summary A major problem in dental care restorations is bacterial infiltration. Bacteria between the tooth and the restoration is a potential cause of postoperative sensitivity, pulp inflammation, and necrosis. In orthodontics, the formation of biofilms during treatment bears the risk of enamel decalcification, cavity formation, and gingival inflammation due to the fact that colonized bacteria are extremely hard to remove in presence of orthodontic appliances. Another related problem is that the current fabrication of dental restorations and braces is labor intensive, requiring highly skilled technicians. Recently, steps have been taken to change the traditional workflow and introduce 3D printing (3DP) technology in this field. 3DP enables a more patient specific way of working, increasing the quality of dental care on the one hand and reducing the costs on the other hand. To address both problems, a highly innovative 3DP antimicrobial polymer system for applications in dentistry and orthodontics will be developed in this proposal. Since the materials will be in contact to or incorporated into the body, attention needs to be paid to render these systems non-toxic and biocompatible. Second, the commercial, IPR and business opportunities of these novel materials will be investigated.
Summary
A major problem in dental care restorations is bacterial infiltration. Bacteria between the tooth and the restoration is a potential cause of postoperative sensitivity, pulp inflammation, and necrosis. In orthodontics, the formation of biofilms during treatment bears the risk of enamel decalcification, cavity formation, and gingival inflammation due to the fact that colonized bacteria are extremely hard to remove in presence of orthodontic appliances. Another related problem is that the current fabrication of dental restorations and braces is labor intensive, requiring highly skilled technicians. Recently, steps have been taken to change the traditional workflow and introduce 3D printing (3DP) technology in this field. 3DP enables a more patient specific way of working, increasing the quality of dental care on the one hand and reducing the costs on the other hand. To address both problems, a highly innovative 3DP antimicrobial polymer system for applications in dentistry and orthodontics will be developed in this proposal. Since the materials will be in contact to or incorporated into the body, attention needs to be paid to render these systems non-toxic and biocompatible. Second, the commercial, IPR and business opportunities of these novel materials will be investigated.
Max ERC Funding
150 000 €
Duration
Start date: 2016-04-01, End date: 2017-09-30
Project acronym APROCS
Project Automated Linear Parameter-Varying Modeling and Control Synthesis for Nonlinear Complex Systems
Researcher (PI) Roland TOTH
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Call Details Starting Grant (StG), PE7, ERC-2016-STG
Summary Linear Parameter-Varying (LPV) systems are flexible mathematical models capable of representing Nonlinear (NL)/Time-Varying (TV) dynamical behaviors of complex physical systems (e.g., wafer scanners, car engines, chemical reactors), often encountered in engineering, via a linear structure. The LPV framework provides computationally efficient and robust approaches to synthesize digital controllers that can ensure desired operation of such systems - making it attractive to (i) high-tech mechatronic, (ii) automotive and (iii) chemical-process applications. Such a framework is important to meet with the increasing operational demands of systems in these industrial sectors and to realize future technological targets. However, recent studies have shown that, to fully exploit the potential of the LPV framework, a number of limiting factors of the underlying theory ask a for serious innovation, as currently it is not understood how to (1) automate exact and low-complexity LPV modeling of real-world applications and how to refine uncertain aspects of these models efficiently by the help of measured data, (2) incorporate control objectives directly into modeling and to develop model reduction approaches for control, and (3) how to see modeling & control synthesis as a unified, closed-loop system synthesis approach directly oriented for the underlying NL/TV system. Furthermore, due to the increasingly cyber-physical nature of applications, (4) control synthesis is needed in a plug & play fashion, where if sub-systems are modified or exchanged, then the control design and the model of the whole system are only incrementally updated. This project aims to surmount Challenges (1)-(4) by establishing an innovative revolution of the LPV framework supported by a software suite and extensive empirical studies on real-world industrial applications; with a potential to ensure a leading role of technological innovation of the EU in the high-impact industrial sectors (i)-(iii).
Summary
Linear Parameter-Varying (LPV) systems are flexible mathematical models capable of representing Nonlinear (NL)/Time-Varying (TV) dynamical behaviors of complex physical systems (e.g., wafer scanners, car engines, chemical reactors), often encountered in engineering, via a linear structure. The LPV framework provides computationally efficient and robust approaches to synthesize digital controllers that can ensure desired operation of such systems - making it attractive to (i) high-tech mechatronic, (ii) automotive and (iii) chemical-process applications. Such a framework is important to meet with the increasing operational demands of systems in these industrial sectors and to realize future technological targets. However, recent studies have shown that, to fully exploit the potential of the LPV framework, a number of limiting factors of the underlying theory ask a for serious innovation, as currently it is not understood how to (1) automate exact and low-complexity LPV modeling of real-world applications and how to refine uncertain aspects of these models efficiently by the help of measured data, (2) incorporate control objectives directly into modeling and to develop model reduction approaches for control, and (3) how to see modeling & control synthesis as a unified, closed-loop system synthesis approach directly oriented for the underlying NL/TV system. Furthermore, due to the increasingly cyber-physical nature of applications, (4) control synthesis is needed in a plug & play fashion, where if sub-systems are modified or exchanged, then the control design and the model of the whole system are only incrementally updated. This project aims to surmount Challenges (1)-(4) by establishing an innovative revolution of the LPV framework supported by a software suite and extensive empirical studies on real-world industrial applications; with a potential to ensure a leading role of technological innovation of the EU in the high-impact industrial sectors (i)-(iii).
Max ERC Funding
1 493 561 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym ARCAS
Project ARCAS: Analysis of the Route to Commercialisation of MVA based influenza vaccines
Researcher (PI) Albertus Dominicus Marcellinus Erasmus OSTERHAUS
Host Institution (HI) ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Call Details Proof of Concept (PoC), PC1, ERC-2012-PoC
Summary ARCAS will investigate the commercial potential and commercialization strategy of a platform of continuously updated repository of pandemic influenza vaccine candidates that was developed under the ERC project FLUPLAN. This platform is based on a novel vector technology using recombinant modified vaccinia virus Ankara (MVA) to develop pandemic influenza vaccines. There are two major advantages of the platform in comparison to current pandemic influenza vaccine platforms using adjuvanted-inactivated and live-attenuated influenza vaccines: i) the high immunogenicity induced in the absence of adjuvants, even at very low dosages, and ii) higher and faster vaccine production capacity. This addresses today’s key unmet needs of pandemic influenza vaccines: strong and broad immunogenicity as well as virtually unlimited production capacity for large scale vaccination campaigns needed in the face of an emerging influenza pandemic. While FLUPLAN addresses the technical development of the platform, including one of the promising candidate vaccines (MVA-based influenza A/H5N1 vaccine), ARCAS will focus on the commercial potential and the commercialization strategy for the platform. This will be achieved by conducting an extensive market study to determine the potential for the novel vaccine repository platform, by analyzing the IP position to build a solid IP portfolio, and by conducting a technical evaluation on the potential of the platform. This will provide the basis to determine the commercial potential and subsequently the most viable commercialization strategy for the platform, to be detailed in a strategic business plan. Furthermore, as part of the strategic business plan, we aim to develop a sound factsheet that will allow potential commercial partners to invest in the technology, addressing the current influenza market needs, given the competitive advantage offered by the platform.
Summary
ARCAS will investigate the commercial potential and commercialization strategy of a platform of continuously updated repository of pandemic influenza vaccine candidates that was developed under the ERC project FLUPLAN. This platform is based on a novel vector technology using recombinant modified vaccinia virus Ankara (MVA) to develop pandemic influenza vaccines. There are two major advantages of the platform in comparison to current pandemic influenza vaccine platforms using adjuvanted-inactivated and live-attenuated influenza vaccines: i) the high immunogenicity induced in the absence of adjuvants, even at very low dosages, and ii) higher and faster vaccine production capacity. This addresses today’s key unmet needs of pandemic influenza vaccines: strong and broad immunogenicity as well as virtually unlimited production capacity for large scale vaccination campaigns needed in the face of an emerging influenza pandemic. While FLUPLAN addresses the technical development of the platform, including one of the promising candidate vaccines (MVA-based influenza A/H5N1 vaccine), ARCAS will focus on the commercial potential and the commercialization strategy for the platform. This will be achieved by conducting an extensive market study to determine the potential for the novel vaccine repository platform, by analyzing the IP position to build a solid IP portfolio, and by conducting a technical evaluation on the potential of the platform. This will provide the basis to determine the commercial potential and subsequently the most viable commercialization strategy for the platform, to be detailed in a strategic business plan. Furthermore, as part of the strategic business plan, we aim to develop a sound factsheet that will allow potential commercial partners to invest in the technology, addressing the current influenza market needs, given the competitive advantage offered by the platform.
Max ERC Funding
149 840 €
Duration
Start date: 2012-12-01, End date: 2013-11-30
Project acronym ARGO
Project The Quest of the Argonautes - from Myth to Reality
Researcher (PI) JOHN VAN DER OOST
Host Institution (HI) WAGENINGEN UNIVERSITY
Call Details Advanced Grant (AdG), LS1, ERC-2018-ADG
Summary Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Summary
Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Max ERC Funding
2 177 158 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym ARMOS
Project Advanced multifunctional Reactors for green Mobility and Solar fuels
Researcher (PI) Athanasios Konstandopoulos
Host Institution (HI) ETHNIKO KENTRO EREVNAS KAI TECHNOLOGIKIS ANAPTYXIS
Call Details Advanced Grant (AdG), PE8, ERC-2010-AdG_20100224
Summary Green Mobility requires an integrated approach to the chain fuel/engine/emissions. The present project aims at ground breaking advances in the area of Green Mobility by (a) enabling the production of affordable, carbon-neutral, clean, solar fuels using exclusively renewable/recyclable raw materials, namely solar energy, water and captured Carbon Dioxide from combustion power plants (b) developing a highly compact, multifunctional reactor, able to eliminate gaseous and particulate emissions from the exhaust of engines operated on such clean fuels.
The overall research approach will be based on material science, engineering and simulation technology developed by the PI over the past 20 years in the area of Diesel Emission Control Reactors, which will be further extended and cross-fertilized in the area of Solar Thermochemical Reactors, an emerging discipline of high importance for sustainable development, where the PI’s research group has already made significant contributions, and received the 2006 European Commission’s Descartes Prize for the development of the first ever solar reactor, holding the potential to produce on a large scale, pure renewable Hydrogen from the thermochemical splitting of water, also known as the HYDROSOL technology.
Summary
Green Mobility requires an integrated approach to the chain fuel/engine/emissions. The present project aims at ground breaking advances in the area of Green Mobility by (a) enabling the production of affordable, carbon-neutral, clean, solar fuels using exclusively renewable/recyclable raw materials, namely solar energy, water and captured Carbon Dioxide from combustion power plants (b) developing a highly compact, multifunctional reactor, able to eliminate gaseous and particulate emissions from the exhaust of engines operated on such clean fuels.
The overall research approach will be based on material science, engineering and simulation technology developed by the PI over the past 20 years in the area of Diesel Emission Control Reactors, which will be further extended and cross-fertilized in the area of Solar Thermochemical Reactors, an emerging discipline of high importance for sustainable development, where the PI’s research group has already made significant contributions, and received the 2006 European Commission’s Descartes Prize for the development of the first ever solar reactor, holding the potential to produce on a large scale, pure renewable Hydrogen from the thermochemical splitting of water, also known as the HYDROSOL technology.
Max ERC Funding
1 750 000 €
Duration
Start date: 2011-02-01, End date: 2017-01-31
Project acronym ART
Project Development of an Anger Regulation Tool for Hand-Held Devices
Researcher (PI) Sander Leon KOOLE
Host Institution (HI) STICHTING VU
Call Details Proof of Concept (PoC), PC1, ERC-2015-PoC
Summary Our research team at the Amsterdam Emotion regulation Lab (emotionregulationlab.com) has recently established that avoidance movements can lower anger and aggression among individuals with chronic anger management problems. Building on and extending these findings, we propose to develop, test, and market an interactive application that runs on mobile devices such as smart phones and tablets. This Anger Reduction Tool (ART) will consist of a ‘serious game’ that trains people to make avoidance movements to angry faces. The ART will be commercialized through a freemium model, such that it will be made freely available, while users can purchase additional functionalities using bio- and neuro-feedback modules. The ART will be marketed to mental health professionals with clients who are not willing or able to respond to traditional cognitive interventions, such as high school children or lower-educated violent offenders. By harnessing the possibilities of smart technology, the ART allows people to become co-managers of their (mental) health and well-being.
Summary
Our research team at the Amsterdam Emotion regulation Lab (emotionregulationlab.com) has recently established that avoidance movements can lower anger and aggression among individuals with chronic anger management problems. Building on and extending these findings, we propose to develop, test, and market an interactive application that runs on mobile devices such as smart phones and tablets. This Anger Reduction Tool (ART) will consist of a ‘serious game’ that trains people to make avoidance movements to angry faces. The ART will be commercialized through a freemium model, such that it will be made freely available, while users can purchase additional functionalities using bio- and neuro-feedback modules. The ART will be marketed to mental health professionals with clients who are not willing or able to respond to traditional cognitive interventions, such as high school children or lower-educated violent offenders. By harnessing the possibilities of smart technology, the ART allows people to become co-managers of their (mental) health and well-being.
Max ERC Funding
150 000 €
Duration
Start date: 2017-01-01, End date: 2018-06-30
Project acronym ARTECHNE
Project Technique in the Arts. Concepts, Practices, Expertise (1500-1950)
Researcher (PI) Sven Georges Mathieu Dupré
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Consolidator Grant (CoG), SH5, ERC-2014-CoG
Summary The transmission of ‘technique’ in art has been a conspicuous ‘black box’ resisting analysis. The tools of the humanities used to study the transmission of ideas and concepts are insufficient when it comes to understanding the transmission of something as non-propositional and non-verbal as ‘technique’. The insights of the neurosciences in, for example, the acquisition and transmission of drawing skills are not yet sufficiently advanced to be historically restrictive. However, only in the most recent years, the history of science and technology has turned to how-to instructions as given in recipes. This project proposes to undertake the experimental reconstruction of historical recipes to finally open the black box of the transmission of technique in the visual and decorative arts. Considering ‘technique’ as a textual, material and social practice, this project will write a long-term history of the theory and practice of the study of ‘technique’ in the visual and decorative arts between 1500 and 1950. The three central research questions here are: (1) what is technique in the visual and decorative arts, (2) how is technique transmitted and studied, and (3) who is considered expert in technique, and why? This project will make a breakthrough in our understanding of the transmission of technique in the arts by integrating methodologies typical for the humanities and historical disciplines with laboratory work. Also, by providing a history of technique in the arts, this project lays the historical foundations of the epistemologies of conservation, restoration and technical art history precisely at a moment of greatest urgency. The connection between the history of science and technology and the expertise in conservation, restoration and technical art history (in the Ateliergebouw in Amsterdam) this project envisions builds the intellectual infrastructure of a new field of interdisciplinary research, unique in Europe.
Summary
The transmission of ‘technique’ in art has been a conspicuous ‘black box’ resisting analysis. The tools of the humanities used to study the transmission of ideas and concepts are insufficient when it comes to understanding the transmission of something as non-propositional and non-verbal as ‘technique’. The insights of the neurosciences in, for example, the acquisition and transmission of drawing skills are not yet sufficiently advanced to be historically restrictive. However, only in the most recent years, the history of science and technology has turned to how-to instructions as given in recipes. This project proposes to undertake the experimental reconstruction of historical recipes to finally open the black box of the transmission of technique in the visual and decorative arts. Considering ‘technique’ as a textual, material and social practice, this project will write a long-term history of the theory and practice of the study of ‘technique’ in the visual and decorative arts between 1500 and 1950. The three central research questions here are: (1) what is technique in the visual and decorative arts, (2) how is technique transmitted and studied, and (3) who is considered expert in technique, and why? This project will make a breakthrough in our understanding of the transmission of technique in the arts by integrating methodologies typical for the humanities and historical disciplines with laboratory work. Also, by providing a history of technique in the arts, this project lays the historical foundations of the epistemologies of conservation, restoration and technical art history precisely at a moment of greatest urgency. The connection between the history of science and technology and the expertise in conservation, restoration and technical art history (in the Ateliergebouw in Amsterdam) this project envisions builds the intellectual infrastructure of a new field of interdisciplinary research, unique in Europe.
Max ERC Funding
1 907 944 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym ARTimmune
Project Programmable ARTificial immune systems to fight cancer
Researcher (PI) Carl FIGDOR
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), LS7, ERC-2018-ADG
Summary Immunotherapy has entered centre stage as a novel treatment modality for cancer. Notwithstanding this major step forward, toxicity and immunosuppression remain major obstacles, and illustrate the pressing need for more powerful and specific immunotherapies against cancer. To overcome these roadblocks, in ARTimmune, I propose to follow a radically different approach by developing local rather than systemic immunotherapies. Taking advantage of the architecture of a lymph node (LN), I aim to design fully synthetic immune niches to locally instruct immune cell function. I hypothesize that programmable synthetic immune niches, when injected next to a tumour, will act as local powerhouses to generate bursts of cytotoxic T cells for tumour destruction, without toxic side effects. Single cell transcriptomics on LN, obtained from patients that are vaccinated against cancer, will provide unique insight in communication within immune cell clusters and provide a blueprint for the intelligent design of synthetic immune niches. Chemical tools will be used to build branched polymeric structures decorated with immunomodulating molecules to mimic LN architecture. These will be injected, mixed with sponge-like scaffolds to provide porosity needed for immune cell infiltration. Programming of immune cell function will be accomplished by in vivo targeting- and proteolytic activation- of immunomodulators for fine-tuning, and to extend the life span of these local powerhouses. The innovative character of ARTimmune comes from: 1) novel fundamental immunological insight in complex communication within LN cell clusters, 2) a revolutionary new approach in immunotherapy, by the development of 3) injectable- and 4) programmable- synthetic immune niches by state-of-the-art chemical technology. When successful, it will revolutionize cancer immunotherapy, moving from maximal tolerable dose systemic treatment with significant toxicity to local low dose treatment in the direct vicinity of a tumour
Summary
Immunotherapy has entered centre stage as a novel treatment modality for cancer. Notwithstanding this major step forward, toxicity and immunosuppression remain major obstacles, and illustrate the pressing need for more powerful and specific immunotherapies against cancer. To overcome these roadblocks, in ARTimmune, I propose to follow a radically different approach by developing local rather than systemic immunotherapies. Taking advantage of the architecture of a lymph node (LN), I aim to design fully synthetic immune niches to locally instruct immune cell function. I hypothesize that programmable synthetic immune niches, when injected next to a tumour, will act as local powerhouses to generate bursts of cytotoxic T cells for tumour destruction, without toxic side effects. Single cell transcriptomics on LN, obtained from patients that are vaccinated against cancer, will provide unique insight in communication within immune cell clusters and provide a blueprint for the intelligent design of synthetic immune niches. Chemical tools will be used to build branched polymeric structures decorated with immunomodulating molecules to mimic LN architecture. These will be injected, mixed with sponge-like scaffolds to provide porosity needed for immune cell infiltration. Programming of immune cell function will be accomplished by in vivo targeting- and proteolytic activation- of immunomodulators for fine-tuning, and to extend the life span of these local powerhouses. The innovative character of ARTimmune comes from: 1) novel fundamental immunological insight in complex communication within LN cell clusters, 2) a revolutionary new approach in immunotherapy, by the development of 3) injectable- and 4) programmable- synthetic immune niches by state-of-the-art chemical technology. When successful, it will revolutionize cancer immunotherapy, moving from maximal tolerable dose systemic treatment with significant toxicity to local low dose treatment in the direct vicinity of a tumour
Max ERC Funding
2 500 000 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
