Project acronym 1st-principles-discs
Project A First Principles Approach to Accretion Discs
Researcher (PI) Martin Elias Pessah
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE9, ERC-2012-StG_20111012
Summary Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Summary
Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Max ERC Funding
1 793 697 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym 2-3-AUT
Project Surfaces, 3-manifolds and automorphism groups
Researcher (PI) Nathalie Wahl
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE1, ERC-2009-StG
Summary The scientific goal of the proposal is to answer central questions related to diffeomorphism groups of manifolds of dimension 2 and 3, and to their deformation invariant analogs, the mapping class groups. While the classification of surfaces has been known for more than a century, their automorphism groups have yet to be fully understood. Even less is known about diffeomorphisms of 3-manifolds despite much interest, and the objects here have only been classified recently, by the breakthrough work of Perelman on the Poincar\'e and geometrization conjectures. In dimension 2, I will focus on the relationship between mapping class groups and topological conformal field theories, with applications to Hochschild homology. In dimension 3, I propose to compute the stable homology of classifying spaces of diffeomorphism groups and mapping class groups, as well as study the homotopy type of the space of diffeomorphisms. I propose moreover to establish homological stability theorems in the wider context of automorphism groups and more general families of groups. The project combines breakthrough methods from homotopy theory with methods from differential and geometric topology. The research team will consist of 3 PhD students, and 4 postdocs, which I will lead.
Summary
The scientific goal of the proposal is to answer central questions related to diffeomorphism groups of manifolds of dimension 2 and 3, and to their deformation invariant analogs, the mapping class groups. While the classification of surfaces has been known for more than a century, their automorphism groups have yet to be fully understood. Even less is known about diffeomorphisms of 3-manifolds despite much interest, and the objects here have only been classified recently, by the breakthrough work of Perelman on the Poincar\'e and geometrization conjectures. In dimension 2, I will focus on the relationship between mapping class groups and topological conformal field theories, with applications to Hochschild homology. In dimension 3, I propose to compute the stable homology of classifying spaces of diffeomorphism groups and mapping class groups, as well as study the homotopy type of the space of diffeomorphisms. I propose moreover to establish homological stability theorems in the wider context of automorphism groups and more general families of groups. The project combines breakthrough methods from homotopy theory with methods from differential and geometric topology. The research team will consist of 3 PhD students, and 4 postdocs, which I will lead.
Max ERC Funding
724 992 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym 20SComplexity
Project An integrative approach to uncover the multilevel regulation of 20S proteasome degradation
Researcher (PI) Michal Sharon
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Starting Grant (StG), LS1, ERC-2014-STG
Summary For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route.
To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation:
Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome.
Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function.
Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach.
Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.
Summary
For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route.
To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation:
Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome.
Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function.
Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach.
Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym 20SInhibitor
Project Selective 20S proteasome inhibition for multiple myeloma therapy
Researcher (PI) Michal SHARON
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary Multiple myeloma (MM) is a cancer of plasma cells, that is incurable, and the second most common form of blood cancer. Proteasome inhibitors (PIs) are considered a mainstay in the treatment of MM and mantle cell lymphoma (MCL). Current drugs, based on PIs however, target the chymotrypsin-like activity of the 20S proteasome, and inhibit the activities of both the 20S and 26S proteasomes. Thus, it is possible that selective drug intervention specifically inhibiting only the 20S proteasomes will reduce toxicity, and minimize the deleterious side effects of the current therapeutic regimens.
Our preliminary work revealed a family of 20S proteasome inhibitors, which we termed Catalytic Core Regulators (CCRs) that selectively target the 20S proteasome rather than the 26S complex. Based on sequence motif and structural elements of the CCRs we have designed an artificial protein that is capable of inhibiting the 20S proteasome. We anticipate that these findings will lead to the design of synthetic proteins, peptides or peptidomimetic compounds targeting cancer cells more specifically. This specificity will pose the compounds in an attractive light for using them in various therapeutic applications.
What is exciting from the commercialization perspective, is that pharmaceutical research has switched to revisit the use of peptides as therapeutics. Pharmaceutical companies have seen the development of peptides as a promising direction to lower their risk position. Overall, peptide therapeutics have a 20% chance of receiving regulatory approval, a probability that is 50% higher than that for the approval of small molecules, which form the basis of so called traditional drugs.
In the project, we will carry out actions, which will equip us with the sufficient IP protection strategy, business strategy, industry networks and initial contacts for taking the innovation out from the laboratory to next phase in developing therapy first for MM and MCL later on.
Summary
Multiple myeloma (MM) is a cancer of plasma cells, that is incurable, and the second most common form of blood cancer. Proteasome inhibitors (PIs) are considered a mainstay in the treatment of MM and mantle cell lymphoma (MCL). Current drugs, based on PIs however, target the chymotrypsin-like activity of the 20S proteasome, and inhibit the activities of both the 20S and 26S proteasomes. Thus, it is possible that selective drug intervention specifically inhibiting only the 20S proteasomes will reduce toxicity, and minimize the deleterious side effects of the current therapeutic regimens.
Our preliminary work revealed a family of 20S proteasome inhibitors, which we termed Catalytic Core Regulators (CCRs) that selectively target the 20S proteasome rather than the 26S complex. Based on sequence motif and structural elements of the CCRs we have designed an artificial protein that is capable of inhibiting the 20S proteasome. We anticipate that these findings will lead to the design of synthetic proteins, peptides or peptidomimetic compounds targeting cancer cells more specifically. This specificity will pose the compounds in an attractive light for using them in various therapeutic applications.
What is exciting from the commercialization perspective, is that pharmaceutical research has switched to revisit the use of peptides as therapeutics. Pharmaceutical companies have seen the development of peptides as a promising direction to lower their risk position. Overall, peptide therapeutics have a 20% chance of receiving regulatory approval, a probability that is 50% higher than that for the approval of small molecules, which form the basis of so called traditional drugs.
In the project, we will carry out actions, which will equip us with the sufficient IP protection strategy, business strategy, industry networks and initial contacts for taking the innovation out from the laboratory to next phase in developing therapy first for MM and MCL later on.
Max ERC Funding
150 000 €
Duration
Start date: 2019-04-01, End date: 2020-09-30
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 321
Project from Cubic To Linear complexity in computational electromagnetics
Researcher (PI) Francesco Paolo ANDRIULLI
Host Institution (HI) POLITECNICO DI TORINO
Call Details Consolidator Grant (CoG), PE7, ERC-2016-COG
Summary Computational Electromagnetics (CEM) is the scientific field at the origin of all new modeling and simulation tools required by the constantly arising design challenges of emerging and future technologies in applied electromagnetics. As in many other technological fields, however, the trend in all emerging technologies in electromagnetic engineering is going towards miniaturized, higher density and multi-scale scenarios. Computationally speaking this translates in the steep increase of the number of degrees of freedom. Given that the design cost (the cost of a multi-right-hand side problem dominated by matrix inversion) can scale as badly as cubically with these degrees of freedom, this fact, as pointed out by many, will sensibly compromise the practical impact of CEM on future and emerging technologies.
For this reason, the CEM scientific community has been looking for years for a FFT-like paradigm shift: a dynamic fast direct solver providing a design cost that would scale only linearly with the degrees of freedom. Such a fast solver is considered today a Holy Grail of the discipline.
The Grand Challenge of 321 will be to tackle this Holy Grail in Computational Electromagnetics by investigating a dynamic Fast Direct Solver for Maxwell Problems that would run in a linear-instead-of-cubic complexity for an arbitrary number and configuration of degrees of freedom.
The failure of all previous attempts will be overcome by a game-changing transformation of the CEM classical problem that will leverage on a recent breakthrough of the PI. Starting from this, the project will investigate an entire new paradigm for impacting algorithms to achieve this grand challenge.
The impact of the FFT’s quadratic-to-linear paradigm shift shows how computational complexity reductions can be groundbreaking on applications. The cubic-to-linear paradigm shift, which the 321 project will aim for, will have such a rupturing impact on electromagnetic science and technology.
Summary
Computational Electromagnetics (CEM) is the scientific field at the origin of all new modeling and simulation tools required by the constantly arising design challenges of emerging and future technologies in applied electromagnetics. As in many other technological fields, however, the trend in all emerging technologies in electromagnetic engineering is going towards miniaturized, higher density and multi-scale scenarios. Computationally speaking this translates in the steep increase of the number of degrees of freedom. Given that the design cost (the cost of a multi-right-hand side problem dominated by matrix inversion) can scale as badly as cubically with these degrees of freedom, this fact, as pointed out by many, will sensibly compromise the practical impact of CEM on future and emerging technologies.
For this reason, the CEM scientific community has been looking for years for a FFT-like paradigm shift: a dynamic fast direct solver providing a design cost that would scale only linearly with the degrees of freedom. Such a fast solver is considered today a Holy Grail of the discipline.
The Grand Challenge of 321 will be to tackle this Holy Grail in Computational Electromagnetics by investigating a dynamic Fast Direct Solver for Maxwell Problems that would run in a linear-instead-of-cubic complexity for an arbitrary number and configuration of degrees of freedom.
The failure of all previous attempts will be overcome by a game-changing transformation of the CEM classical problem that will leverage on a recent breakthrough of the PI. Starting from this, the project will investigate an entire new paradigm for impacting algorithms to achieve this grand challenge.
The impact of the FFT’s quadratic-to-linear paradigm shift shows how computational complexity reductions can be groundbreaking on applications. The cubic-to-linear paradigm shift, which the 321 project will aim for, will have such a rupturing impact on electromagnetic science and technology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym 3D-COUNT
Project 3D-Integrated single photon detector
Researcher (PI) Fabio SCIARRINO
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Proof of Concept (PoC), PC1, ERC-2015-PoC
Summary Photonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers.
The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems.
In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.
Summary
Photonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers.
The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems.
In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.
Max ERC Funding
150 000 €
Duration
Start date: 2016-02-01, End date: 2017-07-31
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
