Project acronym NaMic
Project Nanowire Atomic Force Microscopy for Real Time Imaging of Nanoscale Biological Processes
Researcher (PI) Georg Ernest Fantner
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE3, ERC-2012-StG_20111012
Summary Short summary:
The ability to measure structures with nanoscale resolution continues to transform physics, materials science and life science alike. Nevertheless, while there are excellent tools to obtain detailed molecular-level static structure (for example in biology), there are very few tools to develop an understanding of how these structures change dynamically as they fulfill their biological function. New biologically-compatible, high-speed nanoscale characterization technologies are required to perform these measurements. In this project, we will develop a nanowire-based, high-speed atomic force microscope (NW-HS-AFM) capable of imaging the dynamics of molecular processes on living cells. We will use this instrument to study the dynamic pore-formation mechanisms of novel peptide antibiotics. This increase in performance over current AFMs will be achieved through the use of electron-beam-deposited nanogranular tunneling resistors on prefabricated nanowire AFM cantilevers. By combining these cantilevers with our state of the art high-speed AFM technology, we expect to obtain nanoscale-resolution images of protein pores on living cells at rates of tens of milliseconds per image. This capability will open a whole new arena for seeing nanoscale life in action.
Summary
Short summary:
The ability to measure structures with nanoscale resolution continues to transform physics, materials science and life science alike. Nevertheless, while there are excellent tools to obtain detailed molecular-level static structure (for example in biology), there are very few tools to develop an understanding of how these structures change dynamically as they fulfill their biological function. New biologically-compatible, high-speed nanoscale characterization technologies are required to perform these measurements. In this project, we will develop a nanowire-based, high-speed atomic force microscope (NW-HS-AFM) capable of imaging the dynamics of molecular processes on living cells. We will use this instrument to study the dynamic pore-formation mechanisms of novel peptide antibiotics. This increase in performance over current AFMs will be achieved through the use of electron-beam-deposited nanogranular tunneling resistors on prefabricated nanowire AFM cantilevers. By combining these cantilevers with our state of the art high-speed AFM technology, we expect to obtain nanoscale-resolution images of protein pores on living cells at rates of tens of milliseconds per image. This capability will open a whole new arena for seeing nanoscale life in action.
Max ERC Funding
1 264 640 €
Duration
Start date: 2012-12-01, End date: 2017-11-30
Project acronym NANOMRI
Project Three-dimensional Magnetic Resonance Imaging at Molecular Resolution
Researcher (PI) Christian Degen
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), LS1, ERC-2012-StG_20111109
Summary "Determination of the atomic structure of large and complex macromolecules, indispensable for the understanding of the mechanisms of biological processes, is one of the most difficult problems in molecular biology. Examples of such structures include subcellular entities, giant protein and nucleic acid assemblies, molecular machines, fibrils, membrane proteins, as well as enveloped viruses and small bacteria. The standard tools for delivering structures at atomic resolution, X-ray crystallography and NMR spectroscopy, are overwhelmed by the complexity of such large assemblies, while cryo-electron microscopy, the highest resolution 3D microscopy used by structural biologists, is hindered by heterogeneity and moreover suffers from radiation damage and low contrast.
In this project we propose to develop and apply high-resolution MRI for the direct 3D imaging of macromolecules, comparable to electron microscopy in resolution, but without the need for averaging or staining, and with the unique contrast modalities well-known from clinical applications. Our approach is based on magnetic resonance force microscopy (MRFM), a scanning-probe variety of MRI that has recently enabled 3D imaging of individual virus particles at a spatial resolution of about 5 nm. Our effort will focus on two areas: In a first part we will lay the conceptual and instrumental groundwork needed to make this new technology applicable to biomolecules, including an improvement of the resolution to 1 nm, selective image contrast by stable-isotope labeling, and image reconstruction. In a second part we will apply MRFM to investigate four model systems carefully selected for their structural and biological relevance, including two Amyloid fibrils, a heat-shock protein, and modified virus capsids. The experiments are set to demonstrate the future potential of MRFM for elucidating the large number of disordered and heterogeneous complexes inaccessible to more established structure determination methods."
Summary
"Determination of the atomic structure of large and complex macromolecules, indispensable for the understanding of the mechanisms of biological processes, is one of the most difficult problems in molecular biology. Examples of such structures include subcellular entities, giant protein and nucleic acid assemblies, molecular machines, fibrils, membrane proteins, as well as enveloped viruses and small bacteria. The standard tools for delivering structures at atomic resolution, X-ray crystallography and NMR spectroscopy, are overwhelmed by the complexity of such large assemblies, while cryo-electron microscopy, the highest resolution 3D microscopy used by structural biologists, is hindered by heterogeneity and moreover suffers from radiation damage and low contrast.
In this project we propose to develop and apply high-resolution MRI for the direct 3D imaging of macromolecules, comparable to electron microscopy in resolution, but without the need for averaging or staining, and with the unique contrast modalities well-known from clinical applications. Our approach is based on magnetic resonance force microscopy (MRFM), a scanning-probe variety of MRI that has recently enabled 3D imaging of individual virus particles at a spatial resolution of about 5 nm. Our effort will focus on two areas: In a first part we will lay the conceptual and instrumental groundwork needed to make this new technology applicable to biomolecules, including an improvement of the resolution to 1 nm, selective image contrast by stable-isotope labeling, and image reconstruction. In a second part we will apply MRFM to investigate four model systems carefully selected for their structural and biological relevance, including two Amyloid fibrils, a heat-shock protein, and modified virus capsids. The experiments are set to demonstrate the future potential of MRFM for elucidating the large number of disordered and heterogeneous complexes inaccessible to more established structure determination methods."
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym NANOSOLID
Project Chemically Engineered Nanocrystal Solids
Researcher (PI) Maksym Kovalenko
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), PE5, ERC-2012-StG_20111012
Summary "Many materials in the form of well-defined nanoscale crystals (“nanocrystals”) exhibit unique properties due to size effects and large surface-to-volume ratios. Yet it is clear that the utilization of nanomaterials in modern technologies requires their integration into solid-state structures with programmable electronic, magnetic and optical properties. The clear challenge is the rational design of this novel type of condensed matter, in which the size-tunable individual properties of nanoscale building blocks are enhanced by their interactions and by the macroscopic properties of their ensembles. The project NANOSOLID will rethink existing approaches and propose radically new strategies for the bottom-up assembly of inorganic entities of various dimensionalities into functional inorganic materials. We identified two clear and interlinked needs that will be addressed: the proper design and understanding of nanocrystal surface chemistry, and the unconventional assembly of nanocrystals into dense nanostructured solids. The union of modern concepts from molecular and supramolecular chemistry will be used to develop nanosolids with predictable geometries and functionalities. We will combine colloidal nanocrystals with other well-established classes of materials aiming at previously unknown crystalline structures composed of strongly interacting species in search for ground-breaking advances in materials design. Among the possibilities for these investigations are covalent and non-covalent, directional and non-directional binding modes, and specific and non-specific interparticle interactions. Together, this project will contribute significantly to the fundamental knowledge about the nanocrystal surface, and will develop new synthetic design tools for complex inorganic solids. Overall, the new materials design platform is expected to bring the long-awaited innovative solutions in energy research, particularly in the areas of thin-film devices for energy conversion and storage."
Summary
"Many materials in the form of well-defined nanoscale crystals (“nanocrystals”) exhibit unique properties due to size effects and large surface-to-volume ratios. Yet it is clear that the utilization of nanomaterials in modern technologies requires their integration into solid-state structures with programmable electronic, magnetic and optical properties. The clear challenge is the rational design of this novel type of condensed matter, in which the size-tunable individual properties of nanoscale building blocks are enhanced by their interactions and by the macroscopic properties of their ensembles. The project NANOSOLID will rethink existing approaches and propose radically new strategies for the bottom-up assembly of inorganic entities of various dimensionalities into functional inorganic materials. We identified two clear and interlinked needs that will be addressed: the proper design and understanding of nanocrystal surface chemistry, and the unconventional assembly of nanocrystals into dense nanostructured solids. The union of modern concepts from molecular and supramolecular chemistry will be used to develop nanosolids with predictable geometries and functionalities. We will combine colloidal nanocrystals with other well-established classes of materials aiming at previously unknown crystalline structures composed of strongly interacting species in search for ground-breaking advances in materials design. Among the possibilities for these investigations are covalent and non-covalent, directional and non-directional binding modes, and specific and non-specific interparticle interactions. Together, this project will contribute significantly to the fundamental knowledge about the nanocrystal surface, and will develop new synthetic design tools for complex inorganic solids. Overall, the new materials design platform is expected to bring the long-awaited innovative solutions in energy research, particularly in the areas of thin-film devices for energy conversion and storage."
Max ERC Funding
1 490 319 €
Duration
Start date: 2012-12-01, End date: 2017-11-30
Project acronym NAQUOP
Project Nanodevices for Quantum Optics
Researcher (PI) Valery Zwiller
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), PE3, ERC-2012-StG_20111012
Summary We propose developing a nanodevice toolbox for single photon quantum optics. A scalable scheme to generate indistinguishable single photons, an interface to couple single photon polarization to a single electron spin and high efficiency single photon detectors represent the core of the scientific problems to be addressed in this project.
We set the following research objectives: 1- Understand to what extent quantum dots can be made indistinguishable. 2- Interface coherently single photons to single electron spins via strain engineering in quantum dots. 3- Gain a better understanding of the limits to time resolution and detection efficiency of ultrafast superconducting single photon detectors.
The proposed research effort will yield novel experiments: the realization of scalable indistinguishable quantum dot sources by frequency locking single quantum dots to atomic transitions, the demonstration of new selection rules in semiconductor nanostructures to couple photon polarization to the electron spin only, the development of ultrafast and high efficiency single photon and single plasmon detectors and their implementation in two photon interference and quantum plasmonics experiments.
To carry out the work, multidisciplinary efforts where nanofabrication, quantum optics, semiconductor and superconductor physics will be merged to demonstrate the scalability of quantum dots for quantum information processing, providing crucial new knowledge in single photon optics at the nanoscale. The impact of the project will be important and far reaching as it will address fundamental questions related to the scalability of quantum indistinguishability of remote nanostructures.
Summary
We propose developing a nanodevice toolbox for single photon quantum optics. A scalable scheme to generate indistinguishable single photons, an interface to couple single photon polarization to a single electron spin and high efficiency single photon detectors represent the core of the scientific problems to be addressed in this project.
We set the following research objectives: 1- Understand to what extent quantum dots can be made indistinguishable. 2- Interface coherently single photons to single electron spins via strain engineering in quantum dots. 3- Gain a better understanding of the limits to time resolution and detection efficiency of ultrafast superconducting single photon detectors.
The proposed research effort will yield novel experiments: the realization of scalable indistinguishable quantum dot sources by frequency locking single quantum dots to atomic transitions, the demonstration of new selection rules in semiconductor nanostructures to couple photon polarization to the electron spin only, the development of ultrafast and high efficiency single photon and single plasmon detectors and their implementation in two photon interference and quantum plasmonics experiments.
To carry out the work, multidisciplinary efforts where nanofabrication, quantum optics, semiconductor and superconductor physics will be merged to demonstrate the scalability of quantum dots for quantum information processing, providing crucial new knowledge in single photon optics at the nanoscale. The impact of the project will be important and far reaching as it will address fundamental questions related to the scalability of quantum indistinguishability of remote nanostructures.
Max ERC Funding
1 500 000 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym NEOTROPICS
Project The Past, Present and Future of Neotropical Biodiversity
Researcher (PI) Alexandre Marcos Antonelli
Host Institution (HI) GOETEBORGS UNIVERSITET
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary The American tropics – the Neotropics – comprise more species than any other region on Earth, including thousands of species used as crops, medicines and crafts. Understanding the evolution of this biodiversity and predicting the effects of climate and habitat changes on species losses constitute a major scientific challenge.
This project will:
1) Estimate the rates of historical migration, speciation and extinction among and within all major Neotropical biomes and regions, thereby identifying key areas for ‘evolutionary’ conservation (i.e., those necessary for biotic interchange and vegetation shifts, and those that may function as ‘species pumps’ to the rest of the continent).
2) Test competing hypotheses of speciation (soil specialisation, temperature increases, polyploidy, habitat shifts, range expansion) for the two main centres of Neotropical biodiversity: the tropical Andes and Amazonia.
3) Produce new estimates on species losses due to on-going climate and habitat changes based on our new findings in 1) and 2) above.
To achieve these goals we will develop novel bioinformatics pipelines that will greatly improve our use of biological databases. We will analyse DNA sequences, georeferences and biotic traits for tens of thousands of plant and animal species. Our tools will enable continuously up-to-date inferences and allow the easy integration of new data by students and researchers interested in the evolution of particular species groups or biomes.
This is a multi-disciplinary project that requires a wide range of skills in molecular phylogenetics, bioinformatics, field botany, ecology and palaeontology. It will greatly profit from the well-established scientific network I have built up in my career, the vast collections of Neotropical species deposited at European natural history collections, and the excellent laboratory and cultivation facilities available in Gothenburg, Sweden.
Summary
The American tropics – the Neotropics – comprise more species than any other region on Earth, including thousands of species used as crops, medicines and crafts. Understanding the evolution of this biodiversity and predicting the effects of climate and habitat changes on species losses constitute a major scientific challenge.
This project will:
1) Estimate the rates of historical migration, speciation and extinction among and within all major Neotropical biomes and regions, thereby identifying key areas for ‘evolutionary’ conservation (i.e., those necessary for biotic interchange and vegetation shifts, and those that may function as ‘species pumps’ to the rest of the continent).
2) Test competing hypotheses of speciation (soil specialisation, temperature increases, polyploidy, habitat shifts, range expansion) for the two main centres of Neotropical biodiversity: the tropical Andes and Amazonia.
3) Produce new estimates on species losses due to on-going climate and habitat changes based on our new findings in 1) and 2) above.
To achieve these goals we will develop novel bioinformatics pipelines that will greatly improve our use of biological databases. We will analyse DNA sequences, georeferences and biotic traits for tens of thousands of plant and animal species. Our tools will enable continuously up-to-date inferences and allow the easy integration of new data by students and researchers interested in the evolution of particular species groups or biomes.
This is a multi-disciplinary project that requires a wide range of skills in molecular phylogenetics, bioinformatics, field botany, ecology and palaeontology. It will greatly profit from the well-established scientific network I have built up in my career, the vast collections of Neotropical species deposited at European natural history collections, and the excellent laboratory and cultivation facilities available in Gothenburg, Sweden.
Max ERC Funding
1 499 855 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym NIGOCAT
Project Nature-Inspired Gold Catalytic Tools
Researcher (PI) Cristina Nevado
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Starting Grant (StG), PE5, ERC-2012-StG_20111012
Summary The study of biologically relevant processes heavily relays on “small molecules”. Thus, the demand for novel chemical probes is of highest importance not only for chemistry, but also for closely related disciplines such as biology, medicine or material science. As the construction of complex molecular architectures from chemical building blocks still remains a far-from-routine task, the development of methodologies to increase the control over chemical reactivity and achieve molecular complexity with higher levels of efficiency has become one of the frontier challenges of chemistry in the 21st century.
NIGOCAT aims to substantially contribute towards this goal. The general objective of this proposal is the design, synthesis and application in catalysis of novel, nature-inspired gold(I) and gold(III)-catalytic tools able to mimic nature´s efficiency and exquisite taste for the synthesis and stereoselective functionalization of “small molecules”. The proposed research tackles three main challenges faced by current synthetic methods: 1. Efficient generation of structural complexity; 2. Selective C-H bond functionalization; 3. High levels of stereocontrol in asymmetric catalysis.
We aim to streamline the construction of molecular complexity based on modular, unprecedented multi-center gold factories. Our hypothesis is that the assembly of different reactive sites within a single catalyst will provide an increased level of efficiency in gold-orchestrated catalytic cascades from simple starting materials, thus mimicking the way nature assembles its complex primary metabolites. Second, we aim to tackle the flexible, selective functionalization of C-H bonds using novel metaloenzyme-inspired ligands on gold. Third, we aim to develop novel gold peptide-based catalytic systems as general tools able to provide high levels of absolute stereocontrol in gold catalysis.
Summary
The study of biologically relevant processes heavily relays on “small molecules”. Thus, the demand for novel chemical probes is of highest importance not only for chemistry, but also for closely related disciplines such as biology, medicine or material science. As the construction of complex molecular architectures from chemical building blocks still remains a far-from-routine task, the development of methodologies to increase the control over chemical reactivity and achieve molecular complexity with higher levels of efficiency has become one of the frontier challenges of chemistry in the 21st century.
NIGOCAT aims to substantially contribute towards this goal. The general objective of this proposal is the design, synthesis and application in catalysis of novel, nature-inspired gold(I) and gold(III)-catalytic tools able to mimic nature´s efficiency and exquisite taste for the synthesis and stereoselective functionalization of “small molecules”. The proposed research tackles three main challenges faced by current synthetic methods: 1. Efficient generation of structural complexity; 2. Selective C-H bond functionalization; 3. High levels of stereocontrol in asymmetric catalysis.
We aim to streamline the construction of molecular complexity based on modular, unprecedented multi-center gold factories. Our hypothesis is that the assembly of different reactive sites within a single catalyst will provide an increased level of efficiency in gold-orchestrated catalytic cascades from simple starting materials, thus mimicking the way nature assembles its complex primary metabolites. Second, we aim to tackle the flexible, selective functionalization of C-H bonds using novel metaloenzyme-inspired ligands on gold. Third, we aim to develop novel gold peptide-based catalytic systems as general tools able to provide high levels of absolute stereocontrol in gold catalysis.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym NOVEL_MYOKINE
Project Irisin - a novel myokine protective against metabolic disease
Researcher (PI) Pontus Almer Boström
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Cardiovascular disease and diabetes constitute the major disease burden in the western world with growing morbidity. Exercise is known to ameliorate many of the key processes in the pathogenesis of these diseases, but the underlying mechanism is not clear. Especially little is known about how exercise affects non-muscle tissues such as the heart, fat and liver. Knowledge of such pathways could lead to new therapeutic possibilities for diabetes and cardiovascular diseases.
I have recently discovered a new hormone, named Irisin. Irisin is regulated by PGC1α, secreted from muscle to plasma after exercise and promotes the formation of brown fat via an unknown receptor. Furthermore, irisin is 100% conserved between mice and humans at the amino acid level (89% identity between zebfrafish and human). Nanomolar levels of this protein increase uncoupling protein 1 (UCP1) in cultures of primary white fat cells by 50 fold or more, resulting in very large increases in uncoupled respiration. Perhaps more remarkable, in vivo delivery of irisin stimulates a robust increase in UCP1, increased energy expenditure and reversal of type II diabetes in high fat fed mice. It is thus likely that irisin is responsible for at least some of the beneficial effects of exercise on the browning of adipose tissues and increases in energy expenditure. The therapeutic potential of irisin is obvious; it is a conserved endogenous polypeptide, induced with exercise and with powerful anti-diabetic properties. Irisin could, for example, be administered exogenously, or the secretion of irisin could be enhanced. These approaches, however, require additional studies, and my aim in this project is to advance the knowledge around irisin for future therapeutic testing.
Given success of the ERC grant application, I will move from Harvard/Boston 2012 and start my lab at the department of Cell- and Molecular Biology, Karolinska Institute, Sweden. As seen in my list of publication, Im well prepared for this task
Summary
Cardiovascular disease and diabetes constitute the major disease burden in the western world with growing morbidity. Exercise is known to ameliorate many of the key processes in the pathogenesis of these diseases, but the underlying mechanism is not clear. Especially little is known about how exercise affects non-muscle tissues such as the heart, fat and liver. Knowledge of such pathways could lead to new therapeutic possibilities for diabetes and cardiovascular diseases.
I have recently discovered a new hormone, named Irisin. Irisin is regulated by PGC1α, secreted from muscle to plasma after exercise and promotes the formation of brown fat via an unknown receptor. Furthermore, irisin is 100% conserved between mice and humans at the amino acid level (89% identity between zebfrafish and human). Nanomolar levels of this protein increase uncoupling protein 1 (UCP1) in cultures of primary white fat cells by 50 fold or more, resulting in very large increases in uncoupled respiration. Perhaps more remarkable, in vivo delivery of irisin stimulates a robust increase in UCP1, increased energy expenditure and reversal of type II diabetes in high fat fed mice. It is thus likely that irisin is responsible for at least some of the beneficial effects of exercise on the browning of adipose tissues and increases in energy expenditure. The therapeutic potential of irisin is obvious; it is a conserved endogenous polypeptide, induced with exercise and with powerful anti-diabetic properties. Irisin could, for example, be administered exogenously, or the secretion of irisin could be enhanced. These approaches, however, require additional studies, and my aim in this project is to advance the knowledge around irisin for future therapeutic testing.
Given success of the ERC grant application, I will move from Harvard/Boston 2012 and start my lab at the department of Cell- and Molecular Biology, Karolinska Institute, Sweden. As seen in my list of publication, Im well prepared for this task
Max ERC Funding
1 999 433 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym NovelTAP
Project Novel diagnostic Tools for Alzheimer's and Parkinson's diseases
Researcher (PI) Hilal Ahmed LASHUEL
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Proof of Concept (PoC), PC1, ERC-2012-PoC
Summary Neurodegeneration associated with Parkinson’s (PD) and Alzheimer’s (AD) diseases begins several years prior to the appearance of clinical symptoms and in total, over eight million people in Europe were living with PD or AD in year 2010. Currently, there are no diagnostic tools which allow for early diagnose and/or monitoring the progression these diseases in living patients and the available therapeutic methods only offer transient symptomatic relief. Increasing evidence suggest that early diagnosis and intervention are crucial for any future therapeutic strategies to treat and/or slow the progression of these devastating diseases.
The target of the PoC project is to establish the innovation potential of using the antibodies developed by the PI as diagnostic tools in PD and AD. To fulfill this target, testing and commercialization activities will take place. Specifically, the PoC project will focus on the in-vitro and in-vivo testing of the antibodies using the blood and the cerebrospinal fluid obtained post-mortem from PD and AD patients as well as from animal transgenic models. If successful, these novel antibodies would enable the development of preclinical diagnostic tools for detecting and measuring protein aggregation and other biomarkers, which could ultimately lead to the development of novel and desperately needed pre-diagnostic and therapeutic strategies for treating and/or preventing neurodegeneration in PD and AD. With the help of the PI’s research team, the Technology Transfer Office of EPFL and subcontractors, the PI will develop a commercialization roadmap required to establish proof of concept.
Summary
Neurodegeneration associated with Parkinson’s (PD) and Alzheimer’s (AD) diseases begins several years prior to the appearance of clinical symptoms and in total, over eight million people in Europe were living with PD or AD in year 2010. Currently, there are no diagnostic tools which allow for early diagnose and/or monitoring the progression these diseases in living patients and the available therapeutic methods only offer transient symptomatic relief. Increasing evidence suggest that early diagnosis and intervention are crucial for any future therapeutic strategies to treat and/or slow the progression of these devastating diseases.
The target of the PoC project is to establish the innovation potential of using the antibodies developed by the PI as diagnostic tools in PD and AD. To fulfill this target, testing and commercialization activities will take place. Specifically, the PoC project will focus on the in-vitro and in-vivo testing of the antibodies using the blood and the cerebrospinal fluid obtained post-mortem from PD and AD patients as well as from animal transgenic models. If successful, these novel antibodies would enable the development of preclinical diagnostic tools for detecting and measuring protein aggregation and other biomarkers, which could ultimately lead to the development of novel and desperately needed pre-diagnostic and therapeutic strategies for treating and/or preventing neurodegeneration in PD and AD. With the help of the PI’s research team, the Technology Transfer Office of EPFL and subcontractors, the PI will develop a commercialization roadmap required to establish proof of concept.
Max ERC Funding
147 936 €
Duration
Start date: 2013-07-01, End date: 2014-06-30
Project acronym NucEnv
Project Nuclear Envelope Biogenesis, Function and Dynamics
Researcher (PI) Ulrike Kutay
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), LS1, ERC-2012-ADG_20120314
Summary The nuclear envelope (NE) harbors key roles in cellular and organismal homeostasis, reflected by a variety of diseases caused by mutations in NE proteins. Despite the fundamental role of the NE in protecting and organizing the genome, still little is known about the molecular mechanisms underlying NE biogenesis, dynamics and functionality. We will address 3 open questions in NE biology, using vertebrate cells as model system. (1) To understand how the functional specification of the NE by transmembrane proteins is generated, we will decipher how membrane proteins are sorted to the inner nuclear membrane (INM). To reach this goal, we will define targeting signals and the mode of NPC passage of INM proteins, and identify the molecular requirements for transport. (2) Based on structural analysis, we will investigate how the molecular organization of LINC complexes, which are formed by interacting pairs of SUN and KASH proteins spanning the NE, determines their role in NE architecture and as tethers of the NE to the cytoskeleton. (3) We will study dynamic changes of the NE that occur at the onset of ’open’ mitosis, when the nuclear compartment is disintegrated to allow for the formation of a cytoplasmic mitotic spindle. NE breakdown (NEBD) presents a dramatic change of cellular architecture and comprises a series of events including disassembly of nuclear pore complexes, the nuclear lamina and retraction of NE membranes into the endoplasmic reticulum. To elucidate the molecular mechanisms controlling and executing these steps of nuclear disassembly, we will characterize the cellular machinery involved in NEBD and unravel the molecular function of identified components. All these questions will be addressed by a blend of in vivo approaches relying on high-end fluorescence imaging linked to computational image analysis, RNAi screening, as well as powerful in vitro systems recapitulating protein transport to the INM or NEBD that we have developed, and biochemical methods.
Summary
The nuclear envelope (NE) harbors key roles in cellular and organismal homeostasis, reflected by a variety of diseases caused by mutations in NE proteins. Despite the fundamental role of the NE in protecting and organizing the genome, still little is known about the molecular mechanisms underlying NE biogenesis, dynamics and functionality. We will address 3 open questions in NE biology, using vertebrate cells as model system. (1) To understand how the functional specification of the NE by transmembrane proteins is generated, we will decipher how membrane proteins are sorted to the inner nuclear membrane (INM). To reach this goal, we will define targeting signals and the mode of NPC passage of INM proteins, and identify the molecular requirements for transport. (2) Based on structural analysis, we will investigate how the molecular organization of LINC complexes, which are formed by interacting pairs of SUN and KASH proteins spanning the NE, determines their role in NE architecture and as tethers of the NE to the cytoskeleton. (3) We will study dynamic changes of the NE that occur at the onset of ’open’ mitosis, when the nuclear compartment is disintegrated to allow for the formation of a cytoplasmic mitotic spindle. NE breakdown (NEBD) presents a dramatic change of cellular architecture and comprises a series of events including disassembly of nuclear pore complexes, the nuclear lamina and retraction of NE membranes into the endoplasmic reticulum. To elucidate the molecular mechanisms controlling and executing these steps of nuclear disassembly, we will characterize the cellular machinery involved in NEBD and unravel the molecular function of identified components. All these questions will be addressed by a blend of in vivo approaches relying on high-end fluorescence imaging linked to computational image analysis, RNAi screening, as well as powerful in vitro systems recapitulating protein transport to the INM or NEBD that we have developed, and biochemical methods.
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym OTEGS
Project Organic Thermoelectric Generators
Researcher (PI) Xavier Dominique Etienne Crispin
Host Institution (HI) LINKOPINGS UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2012-StG_20111012
Summary At the moment, there is no viable technology to produce electricity from natural heat sources (T<200°C) and from 50% of the waste heat (electricity production, industries, buildings and transports) stored in large volume of warm fluids (T<200°C). To extract heat from large volumes of fluids, the thermoelectric generators would need to cover large areas in new designed heat exchangers. To develop into a viable technology platform, thermoelectric devices must be fabricated on large areas via low-cost processes. But no thermoelectric material exists for this purpose.
Recently, the applicant has discovered that the low-cost conducting polymer poly(ethylene dioxythiophene) possesses a figure-of-merit ZT=0.25 at room temperature. Conducting polymers can be processed from solution, they are flexible and possess an intrinsic low thermal conductivity. This combination of unique properties motivate further investigations to reveal the true potential of organic materials for thermoelectric applications: this is the essence of this project.
My goal is to organize an interdisciplinary team of researchers focused on the characterization, understanding, design and fabrication of p- and n-doped organic-based thermoelectric materials; and the demonstration of those materials in organic thermoelectric generators (OTEGs). Firstly, we will create the first generation of efficient organic thermoelectric materials with ZT> 0.8 at room temperature: (i) by optimizing not only the power factor but also the thermal conductivity; (ii) by demonstrating that a large power factor is obtained in inorganic-organic nanocomposites. Secondly, we will optimize thermoelectrochemical cells by considering various types of electrolytes.
The research activities proposed are at the cutting edge in material sciences and involve chemical synthesis, interface studies, thermal physics, electrical, electrochemical and structural characterization, device physics. The project is held at Linköping University holding a world leading research in polymer electronics.
Summary
At the moment, there is no viable technology to produce electricity from natural heat sources (T<200°C) and from 50% of the waste heat (electricity production, industries, buildings and transports) stored in large volume of warm fluids (T<200°C). To extract heat from large volumes of fluids, the thermoelectric generators would need to cover large areas in new designed heat exchangers. To develop into a viable technology platform, thermoelectric devices must be fabricated on large areas via low-cost processes. But no thermoelectric material exists for this purpose.
Recently, the applicant has discovered that the low-cost conducting polymer poly(ethylene dioxythiophene) possesses a figure-of-merit ZT=0.25 at room temperature. Conducting polymers can be processed from solution, they are flexible and possess an intrinsic low thermal conductivity. This combination of unique properties motivate further investigations to reveal the true potential of organic materials for thermoelectric applications: this is the essence of this project.
My goal is to organize an interdisciplinary team of researchers focused on the characterization, understanding, design and fabrication of p- and n-doped organic-based thermoelectric materials; and the demonstration of those materials in organic thermoelectric generators (OTEGs). Firstly, we will create the first generation of efficient organic thermoelectric materials with ZT> 0.8 at room temperature: (i) by optimizing not only the power factor but also the thermal conductivity; (ii) by demonstrating that a large power factor is obtained in inorganic-organic nanocomposites. Secondly, we will optimize thermoelectrochemical cells by considering various types of electrolytes.
The research activities proposed are at the cutting edge in material sciences and involve chemical synthesis, interface studies, thermal physics, electrical, electrochemical and structural characterization, device physics. The project is held at Linköping University holding a world leading research in polymer electronics.
Max ERC Funding
1 453 690 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
