Project acronym 2DMATER
Project Controlled Synthesis of Two-Dimensional Nanomaterials for Energy Storage and Conversion
Researcher (PI) Xinliang Feng
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2012-StG_20111012
Summary "Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
Summary
"Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-09-01, End date: 2017-08-31
Project acronym 2D–SYNETRA
Project Two-dimensional colloidal nanostructures - Synthesis and electrical transport
Researcher (PI) Christian Klinke
Host Institution (HI) UNIVERSITAET HAMBURG
Country Germany
Call Details Starting Grant (StG), PE4, ERC-2012-StG_20111012
Summary We propose to develop truly two-dimensional continuous materials and two-dimensional monolayer films composed of individual nanocrystals by the comparatively fast, inexpensive, and scalable colloidal synthesis method. The materials’ properties will be studied in detail, especially regarding their (photo-) electrical transport. This will allow developing new types of device structures, such as Coulomb blockade and field enhancement based transistors.
Recently, we demonstrated the possibility to synthesize in a controlled manner truly two-dimensional colloidal nanostructures. We will investigate their formation mechanism, synthesize further materials as “nanosheets”, develop methodologies to tune their geometrical properties, and study their (photo-) electrical properties.
Furthermore, we will use the Langmuir-Blodgett method to deposit highly ordered monolayers of monodisperse nanoparticles. Such structures show interesting transport properties governed by Coulomb blockade effects known from individual nanoparticles. This leads to semiconductor-like behavior in metal nanoparticle films. The understanding of the electric transport in such “multi-tunnel devices” is still very limited. Thus, we will investigate this concept in detail and take it to its limits. Beside improvement of quality and exchange of material we will tune the nanoparticles’ size and shape in order to gain a deeper understanding of the electrical properties of supercrystallographic assemblies. Furthermore, we will develop device concepts for diode and transistor structures which take into account the novel properties of the low-dimensional assemblies.
Nanosheets and monolayers of nanoparticles truly follow the principle of building devices by the bottom-up approach and allow electric transport measurements in a 2D regime. Highly ordered nanomaterial systems possess easy and reliably to manipulate electronic properties what make them interesting for future (inexpensive) electronic devices.
Summary
We propose to develop truly two-dimensional continuous materials and two-dimensional monolayer films composed of individual nanocrystals by the comparatively fast, inexpensive, and scalable colloidal synthesis method. The materials’ properties will be studied in detail, especially regarding their (photo-) electrical transport. This will allow developing new types of device structures, such as Coulomb blockade and field enhancement based transistors.
Recently, we demonstrated the possibility to synthesize in a controlled manner truly two-dimensional colloidal nanostructures. We will investigate their formation mechanism, synthesize further materials as “nanosheets”, develop methodologies to tune their geometrical properties, and study their (photo-) electrical properties.
Furthermore, we will use the Langmuir-Blodgett method to deposit highly ordered monolayers of monodisperse nanoparticles. Such structures show interesting transport properties governed by Coulomb blockade effects known from individual nanoparticles. This leads to semiconductor-like behavior in metal nanoparticle films. The understanding of the electric transport in such “multi-tunnel devices” is still very limited. Thus, we will investigate this concept in detail and take it to its limits. Beside improvement of quality and exchange of material we will tune the nanoparticles’ size and shape in order to gain a deeper understanding of the electrical properties of supercrystallographic assemblies. Furthermore, we will develop device concepts for diode and transistor structures which take into account the novel properties of the low-dimensional assemblies.
Nanosheets and monolayers of nanoparticles truly follow the principle of building devices by the bottom-up approach and allow electric transport measurements in a 2D regime. Highly ordered nanomaterial systems possess easy and reliably to manipulate electronic properties what make them interesting for future (inexpensive) electronic devices.
Max ERC Funding
1 497 200 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym 2F4BIODYN
Project Two-Field Nuclear Magnetic Resonance Spectroscopy for the Exploration of Biomolecular Dynamics
Researcher (PI) Fabien Ferrage
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Starting Grant (StG), PE4, ERC-2011-StG_20101014
Summary The paradigm of the structure-function relationship in proteins is outdated. Biological macromolecules and supramolecular assemblies are highly dynamic objects. Evidence that their motions are of utmost importance to their functions is regularly identified. The understanding of the physical chemistry of biological processes at an atomic level has to rely not only on the description of structure but also on the characterization of molecular motions.
The investigation of protein motions will be undertaken with a very innovative methodological approach in nuclear magnetic resonance relaxation. In order to widen the ranges of frequencies at which local motions in proteins are probed, we will first use and develop new techniques for a prototype shuttle system for the measurement of relaxation at low fields on a high-field NMR spectrometer. Second, we will develop a novel system: a set of low-field NMR spectrometers designed as accessories for high-field spectrometers. Used in conjunction with the shuttle, this system will offer (i) the sensitivity and resolution (i.e. atomic level information) of a high-field spectrometer (ii) the access to low fields of a relaxometer and (iii) the ability to measure a wide variety of relaxation rates with high accuracy. This system will benefit from the latest technology in homogeneous permanent magnet development to allow a control of spin systems identical to that of a high-resolution probe. This new apparatus will open the way to the use of NMR relaxation at low fields for the refinement of protein motions at an atomic scale.
Applications of this novel approach will focus on the bright side of protein dynamics: (i) the largely unexplored dynamics of intrinsically disordered proteins, and (ii) domain motions in large proteins. In both cases, we will investigate a series of diverse protein systems with implications in development, cancer and immunity.
Summary
The paradigm of the structure-function relationship in proteins is outdated. Biological macromolecules and supramolecular assemblies are highly dynamic objects. Evidence that their motions are of utmost importance to their functions is regularly identified. The understanding of the physical chemistry of biological processes at an atomic level has to rely not only on the description of structure but also on the characterization of molecular motions.
The investigation of protein motions will be undertaken with a very innovative methodological approach in nuclear magnetic resonance relaxation. In order to widen the ranges of frequencies at which local motions in proteins are probed, we will first use and develop new techniques for a prototype shuttle system for the measurement of relaxation at low fields on a high-field NMR spectrometer. Second, we will develop a novel system: a set of low-field NMR spectrometers designed as accessories for high-field spectrometers. Used in conjunction with the shuttle, this system will offer (i) the sensitivity and resolution (i.e. atomic level information) of a high-field spectrometer (ii) the access to low fields of a relaxometer and (iii) the ability to measure a wide variety of relaxation rates with high accuracy. This system will benefit from the latest technology in homogeneous permanent magnet development to allow a control of spin systems identical to that of a high-resolution probe. This new apparatus will open the way to the use of NMR relaxation at low fields for the refinement of protein motions at an atomic scale.
Applications of this novel approach will focus on the bright side of protein dynamics: (i) the largely unexplored dynamics of intrinsically disordered proteins, and (ii) domain motions in large proteins. In both cases, we will investigate a series of diverse protein systems with implications in development, cancer and immunity.
Max ERC Funding
1 462 080 €
Duration
Start date: 2012-01-01, End date: 2017-12-31
Project acronym 2O2ACTIVATION
Project Development of Direct Dehydrogenative Couplings mediated by Dioxygen
Researcher (PI) Frederic William Patureau
Host Institution (HI) RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2016-STG
Summary The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research.
The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation.
The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event.
Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
Summary
The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research.
The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation.
The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event.
Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
Max ERC Funding
1 489 823 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym 3D-FNPWriting
Project Unprecedented spatial control of porosity and functionality in nanoporous membranes through 3D printing and microscopy for polymer writing
Researcher (PI) Annette ANDRIEU-BRUNSEN
Host Institution (HI) TECHNISCHE UNIVERSITAT DARMSTADT
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2018-STG
Summary Membranes are key materials in our life. Nature offers high performance membranes relying on a parallel local regulation of nanopore structure, functional placement, membrane composition and architecture. Existing technological membranes are key materials in separation, recycling, sensing, energy conversion, being essential components for a sustainable future. But their performance is far away from their natural counterparts. One reason for this performance gap is the lack of 3D nanolocal control in membrane design. This applies to each individual nanopore but as well to the membrane architecture. This proposal aims to implement 3D printing (additive manufacturing, top down) and complex near-field and total internal reflection (TIR) high resolution microscopy induced polymer writing (bottom up) to nanolocally control in hierarchical nanoporous membranes spatially and independent of each other: porosity, pore functionalization, membrane architecture, composition. This disruptive technology platform will make accessible to date unachieved, highly accurate asymmetric nanopores and multifunctional, hierarchical membrane architecture/ composition and thus highly selective, directed, transport with tuneable rates. 3D-FNPWriting will demonstrate this for the increasing class of metal nanoparticle/ salt pollutants aiming for tuneable, selective, directed transport based monitoring and recycling instead of size-based filtration, accumulation into sewerage and distribution into nature. Specifically, the potential of this disruptive technology with respect to transport design will be demonstrated for a) a 3D-printed in-situ functionalized nanoporous fiber architecture and b) a printed, nanolocally near-field and TIR-microscopy polymer functionalized membrane representing a thin separation layer. This will open systematic understanding of nanolocal functional control on transport and new perspectives in water/ energy management for future smart industry/ homes.
Summary
Membranes are key materials in our life. Nature offers high performance membranes relying on a parallel local regulation of nanopore structure, functional placement, membrane composition and architecture. Existing technological membranes are key materials in separation, recycling, sensing, energy conversion, being essential components for a sustainable future. But their performance is far away from their natural counterparts. One reason for this performance gap is the lack of 3D nanolocal control in membrane design. This applies to each individual nanopore but as well to the membrane architecture. This proposal aims to implement 3D printing (additive manufacturing, top down) and complex near-field and total internal reflection (TIR) high resolution microscopy induced polymer writing (bottom up) to nanolocally control in hierarchical nanoporous membranes spatially and independent of each other: porosity, pore functionalization, membrane architecture, composition. This disruptive technology platform will make accessible to date unachieved, highly accurate asymmetric nanopores and multifunctional, hierarchical membrane architecture/ composition and thus highly selective, directed, transport with tuneable rates. 3D-FNPWriting will demonstrate this for the increasing class of metal nanoparticle/ salt pollutants aiming for tuneable, selective, directed transport based monitoring and recycling instead of size-based filtration, accumulation into sewerage and distribution into nature. Specifically, the potential of this disruptive technology with respect to transport design will be demonstrated for a) a 3D-printed in-situ functionalized nanoporous fiber architecture and b) a printed, nanolocally near-field and TIR-microscopy polymer functionalized membrane representing a thin separation layer. This will open systematic understanding of nanolocal functional control on transport and new perspectives in water/ energy management for future smart industry/ homes.
Max ERC Funding
1 499 844 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym 3FLEX
Project Three-Component Fermi Gas Lattice Experiment
Researcher (PI) Selim Jochim
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Country Germany
Call Details Starting Grant (StG), PE2, ERC-2011-StG_20101014
Summary Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.
Summary
Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.
Max ERC Funding
1 469 040 €
Duration
Start date: 2011-08-01, End date: 2016-07-31
Project acronym 4DVIDEO
Project 4DVideo: 4D spatio-temporal modeling of real-world events from video streams
Researcher (PI) Marc Pollefeys
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Starting Grant (StG), PE5, ERC-2007-StG
Summary The focus of this project is the development of algorithms that allow one to capture and analyse dynamic events taking place in the real world. For this, we intend to develop smart camera networks that can perform a multitude of observation tasks, ranging from surveillance and tracking to high-fidelity, immersive reconstructions of important dynamic events (i.e. 4D videos). There are many fundamental questions in computer vision associated with these problems. Can the geometric, topologic and photometric properties of the camera network be obtained from live images? What is changing about the environment in which the network is embedded? How much information can be obtained from dynamic events that are observed by the network? What if the camera network consists of a random collection of sensors that happened to observe a particular event (think hand-held cell phone cameras)? Do we need synchronization? Those questions become even more challenging if one considers active camera networks that can adapt to the vision task at hand. How should resources be prioritized for different tasks? Can we derive optimal strategies to control camera parameters such as pan, tilt and zoom, trade-off resolution, frame-rate and bandwidth? More fundamentally, seeing cameras as points that sample incoming light rays and camera networks as a distributed sensor, how does one decide which rays should be sampled? Many of those issues are particularly interesting when we consider time-varying events. Both spatial and temporal resolution are important and heterogeneous frame-rates and resolution can offer advantages. Prior knowledge or information obtained from earlier samples can be used to restrict the possible range of solutions (e.g. smoothness assumption and motion prediction). My goal is to obtain fundamental answers to many of those question based on thorough theoretical analysis combined with practical algorithms that are proven on real applications.
Summary
The focus of this project is the development of algorithms that allow one to capture and analyse dynamic events taking place in the real world. For this, we intend to develop smart camera networks that can perform a multitude of observation tasks, ranging from surveillance and tracking to high-fidelity, immersive reconstructions of important dynamic events (i.e. 4D videos). There are many fundamental questions in computer vision associated with these problems. Can the geometric, topologic and photometric properties of the camera network be obtained from live images? What is changing about the environment in which the network is embedded? How much information can be obtained from dynamic events that are observed by the network? What if the camera network consists of a random collection of sensors that happened to observe a particular event (think hand-held cell phone cameras)? Do we need synchronization? Those questions become even more challenging if one considers active camera networks that can adapt to the vision task at hand. How should resources be prioritized for different tasks? Can we derive optimal strategies to control camera parameters such as pan, tilt and zoom, trade-off resolution, frame-rate and bandwidth? More fundamentally, seeing cameras as points that sample incoming light rays and camera networks as a distributed sensor, how does one decide which rays should be sampled? Many of those issues are particularly interesting when we consider time-varying events. Both spatial and temporal resolution are important and heterogeneous frame-rates and resolution can offer advantages. Prior knowledge or information obtained from earlier samples can be used to restrict the possible range of solutions (e.g. smoothness assumption and motion prediction). My goal is to obtain fundamental answers to many of those question based on thorough theoretical analysis combined with practical algorithms that are proven on real applications.
Max ERC Funding
1 757 422 €
Duration
Start date: 2008-08-01, End date: 2013-11-30
Project acronym 4TH-NU-AVENUE
Project Search for a fourth neutrino with a PBq anti-neutrino source
Researcher (PI) Thierry Michel Rene Lasserre
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Country France
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
Summary Several observed anomalies in neutrino oscillation data can be explained by a hypothetical fourth neutrino separated from the three standard neutrinos by a squared mass difference of a few eV2. This hypothesis can be tested with a PBq (ten kilocurie scale) 144Ce antineutrino beta-source deployed at the center of a large low background liquid scintillator detector, such like Borexino, KamLAND, and SNO+. In particular, the compact size of such a source could yield an energy-dependent oscillating pattern in event spatial distribution that would unambiguously determine neutrino mass differences and mixing angles.
The proposed program aims to perform the necessary research and developments to produce and deploy an intense antineutrino source in a large liquid scintillator detector. Our program will address the definition of the production process of the neutrino source as well as its experimental characterization, the detailed physics simulation of both signal and backgrounds, the complete design and the realization of the thick shielding, the preparation of the interfaces with the antineutrino detector, including the safety and security aspects.
Summary
Several observed anomalies in neutrino oscillation data can be explained by a hypothetical fourth neutrino separated from the three standard neutrinos by a squared mass difference of a few eV2. This hypothesis can be tested with a PBq (ten kilocurie scale) 144Ce antineutrino beta-source deployed at the center of a large low background liquid scintillator detector, such like Borexino, KamLAND, and SNO+. In particular, the compact size of such a source could yield an energy-dependent oscillating pattern in event spatial distribution that would unambiguously determine neutrino mass differences and mixing angles.
The proposed program aims to perform the necessary research and developments to produce and deploy an intense antineutrino source in a large liquid scintillator detector. Our program will address the definition of the production process of the neutrino source as well as its experimental characterization, the detailed physics simulation of both signal and backgrounds, the complete design and the realization of the thick shielding, the preparation of the interfaces with the antineutrino detector, including the safety and security aspects.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym a SMILE
Project analyse Soluble + Membrane complexes with Improved LILBID Experiments
Researcher (PI) Nina Morgner
Host Institution (HI) JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Country Germany
Call Details Starting Grant (StG), PE4, ERC-2013-StG
Summary Crucial processes within cells depend on specific non-covalent interactions which mediate the assembly of proteins and other biomolecules. Deriving structural information to understand the function of these complex systems is the primary goal of Structural Biology.
In this application, the recently developed LILBID method (Laser Induced Liquid Bead Ion Desorption) will be optimized for investigation of macromolecular complexes with a mass accuracy two orders of magnitude better than in 1st generation spectrometers.
Controlled disassembly of the multiprotein complexes in the mass spectrometric analysis while keeping the 3D structure intact, will allow for the determination of complex stoichiometry and connectivity of the constituting proteins. Methods for such controlled disassembly will be developed in two separate units of the proposed LILBID spectrometer, in a collision chamber and in a laser dissociation chamber, enabling gas phase dissociation of protein complexes and removal of excess water/buffer molecules. As a third unit, a chamber allowing determination of ion mobility (IM) will be integrated to determine collisional cross sections (CCS). From CCS, unique information regarding the spatial arrangement of proteins in complexes or subcomplexes will then be obtainable from LILBID.
The proposed design of the new spectrometer will offer fundamentally new possibilities for the investigation of non-covalent RNA, soluble and membrane protein complexes, as well as broadening the applicability of non-covalent MS towards supercomplexes.
Summary
Crucial processes within cells depend on specific non-covalent interactions which mediate the assembly of proteins and other biomolecules. Deriving structural information to understand the function of these complex systems is the primary goal of Structural Biology.
In this application, the recently developed LILBID method (Laser Induced Liquid Bead Ion Desorption) will be optimized for investigation of macromolecular complexes with a mass accuracy two orders of magnitude better than in 1st generation spectrometers.
Controlled disassembly of the multiprotein complexes in the mass spectrometric analysis while keeping the 3D structure intact, will allow for the determination of complex stoichiometry and connectivity of the constituting proteins. Methods for such controlled disassembly will be developed in two separate units of the proposed LILBID spectrometer, in a collision chamber and in a laser dissociation chamber, enabling gas phase dissociation of protein complexes and removal of excess water/buffer molecules. As a third unit, a chamber allowing determination of ion mobility (IM) will be integrated to determine collisional cross sections (CCS). From CCS, unique information regarding the spatial arrangement of proteins in complexes or subcomplexes will then be obtainable from LILBID.
The proposed design of the new spectrometer will offer fundamentally new possibilities for the investigation of non-covalent RNA, soluble and membrane protein complexes, as well as broadening the applicability of non-covalent MS towards supercomplexes.
Max ERC Funding
1 264 477 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym A-LIFE
Project The asymmetry of life: towards a unified view of the emergence of biological homochirality
Researcher (PI) Cornelia MEINERT
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Starting Grant (StG), PE4, ERC-2018-STG
Summary What is responsible for the emergence of homochirality, the almost exclusive use of one enantiomer over its mirror image? And what led to the evolution of life’s homochiral biopolymers, DNA/RNA, proteins and lipids, where all the constituent monomers exhibit the same handedness?
Based on in-situ observations and laboratory studies, we propose that this handedness occurs when chiral biomolecules are synthesized asymmetrically through interaction with circularly polarized photons in interstellar space. The ultimate goal of this project will be to demonstrate how the diverse set of heterogeneous enantioenriched molecules, available from meteoritic impact, assembles into homochiral pre-biopolymers, by simulating the evolutionary stages on early Earth. My recent research has shown that the central chiral unit of RNA, ribose, forms readily under simulated comet conditions and this has provided valuable new insights into the accessibility of precursors of genetic material in interstellar environments. The significance of this project arises due to the current lack of experimental demonstration that amino acids, sugars and lipids can simultaneously and asymmetrically be synthesized by a universal physical selection process.
A synergistic methodology will be developed to build a unified theory for the origin of all chiral biological building blocks and their assembly into homochiral supramolecular entities. For the first time, advanced analyses of astrophysical-relevant samples, asymmetric photochemistry triggered by circularly polarized synchrotron and laser sources, and chiral amplification due to polymerization processes will be combined. Intermediates and autocatalytic reaction kinetics will be monitored and supported by quantum calculations to understand the underlying processes. A unified theory on the asymmetric formation and self-assembly of life’s biopolymers is groundbreaking and will impact the whole conceptual foundation of the origin of life.
Summary
What is responsible for the emergence of homochirality, the almost exclusive use of one enantiomer over its mirror image? And what led to the evolution of life’s homochiral biopolymers, DNA/RNA, proteins and lipids, where all the constituent monomers exhibit the same handedness?
Based on in-situ observations and laboratory studies, we propose that this handedness occurs when chiral biomolecules are synthesized asymmetrically through interaction with circularly polarized photons in interstellar space. The ultimate goal of this project will be to demonstrate how the diverse set of heterogeneous enantioenriched molecules, available from meteoritic impact, assembles into homochiral pre-biopolymers, by simulating the evolutionary stages on early Earth. My recent research has shown that the central chiral unit of RNA, ribose, forms readily under simulated comet conditions and this has provided valuable new insights into the accessibility of precursors of genetic material in interstellar environments. The significance of this project arises due to the current lack of experimental demonstration that amino acids, sugars and lipids can simultaneously and asymmetrically be synthesized by a universal physical selection process.
A synergistic methodology will be developed to build a unified theory for the origin of all chiral biological building blocks and their assembly into homochiral supramolecular entities. For the first time, advanced analyses of astrophysical-relevant samples, asymmetric photochemistry triggered by circularly polarized synchrotron and laser sources, and chiral amplification due to polymerization processes will be combined. Intermediates and autocatalytic reaction kinetics will be monitored and supported by quantum calculations to understand the underlying processes. A unified theory on the asymmetric formation and self-assembly of life’s biopolymers is groundbreaking and will impact the whole conceptual foundation of the origin of life.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym ABIOS
Project ABIOtic Synthesis of RNA: an investigation on how life started before biology existed
Researcher (PI) Guillaume STIRNEMANN
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Starting Grant (StG), PE4, ERC-2017-STG
Summary The emergence of life is one of the most fascinating and yet largely unsolved questions in the natural sciences, and thus a significant challenge for scientists from many disciplines. There is growing evidence that ribonucleic acid (RNA) polymers, which are capable of genetic information storage and self-catalysis, were involved in the early forms of life. But despite recent progress, RNA synthesis without biological machineries is very challenging. The current project aims at understanding how to synthesize RNA in abiotic conditions. I will solve problems associated with three critical aspects of RNA formation that I will rationalize at a molecular level: (i) accumulation of precursors, (ii) formation of a chemical bond between RNA monomers, and (iii) tolerance for alternative backbone sugars or linkages. Because I will study problems ranging from the formation of chemical bonds up to the stability of large biopolymers, I propose an original computational multi-scale approach combining techniques that range from quantum calculations to large-scale all-atom simulations, employed together with efficient enhanced-sampling algorithms, forcefield improvement, cutting-edge analysis methods and model development.
My objectives are the following:
1 • To explain why the poorly-understood thermally-driven process of thermophoresis can contribute to the accumulation of dilute precursors.
2 • To understand why linking RNA monomers with phosphoester bonds is so difficult, to understand the molecular mechanism of possible catalysts and to suggest key improvements.
3 • To rationalize the molecular basis for RNA tolerance for alternative backbone sugars or linkages that have probably been incorporated in abiotic conditions.
This unique in-silico laboratory setup should significantly impact our comprehension of life’s origin by overcoming major obstacles to RNA abiotic formation, and in addition will reveal significant orthogonal outcomes for (bio)technological applications.
Summary
The emergence of life is one of the most fascinating and yet largely unsolved questions in the natural sciences, and thus a significant challenge for scientists from many disciplines. There is growing evidence that ribonucleic acid (RNA) polymers, which are capable of genetic information storage and self-catalysis, were involved in the early forms of life. But despite recent progress, RNA synthesis without biological machineries is very challenging. The current project aims at understanding how to synthesize RNA in abiotic conditions. I will solve problems associated with three critical aspects of RNA formation that I will rationalize at a molecular level: (i) accumulation of precursors, (ii) formation of a chemical bond between RNA monomers, and (iii) tolerance for alternative backbone sugars or linkages. Because I will study problems ranging from the formation of chemical bonds up to the stability of large biopolymers, I propose an original computational multi-scale approach combining techniques that range from quantum calculations to large-scale all-atom simulations, employed together with efficient enhanced-sampling algorithms, forcefield improvement, cutting-edge analysis methods and model development.
My objectives are the following:
1 • To explain why the poorly-understood thermally-driven process of thermophoresis can contribute to the accumulation of dilute precursors.
2 • To understand why linking RNA monomers with phosphoester bonds is so difficult, to understand the molecular mechanism of possible catalysts and to suggest key improvements.
3 • To rationalize the molecular basis for RNA tolerance for alternative backbone sugars or linkages that have probably been incorporated in abiotic conditions.
This unique in-silico laboratory setup should significantly impact our comprehension of life’s origin by overcoming major obstacles to RNA abiotic formation, and in addition will reveal significant orthogonal outcomes for (bio)technological applications.
Max ERC Funding
1 497 031 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym AcetyLys
Project Unravelling the role of lysine acetylation in the regulation of glycolysis in cancer cells through the development of synthetic biology-based tools
Researcher (PI) Eyal Arbely
Host Institution (HI) BEN-GURION UNIVERSITY OF THE NEGEV
Country Israel
Call Details Starting Grant (StG), LS9, ERC-2015-STG
Summary Synthetic biology is an emerging discipline that offers powerful tools to control and manipulate fundamental processes in living matter. We propose to develop and apply such tools to modify the genetic code of cultured mammalian cells and bacteria with the aim to study the role of lysine acetylation in the regulation of metabolism and in cancer development. Thousands of lysine acetylation sites were recently discovered on non-histone proteins, suggesting that acetylation is a widespread and evolutionarily conserved post translational modification, similar in scope to phosphorylation and ubiquitination. Specifically, it has been found that most of the enzymes of metabolic processes—including glycolysis—are acetylated, implying that acetylation is key regulator of cellular metabolism in general and in glycolysis in particular. The regulation of metabolic pathways is of particular importance to cancer research, as misregulation of metabolic pathways, especially upregulation of glycolysis, is common to most transformed cells and is now considered a new hallmark of cancer. These data raise an immediate question: what is the role of acetylation in the regulation of glycolysis and in the metabolic reprogramming of cancer cells? While current methods rely on mutational analyses, we will genetically encode the incorporation of acetylated lysine and directly measure the functional role of each acetylation site in cancerous and non-cancerous cell lines. Using this methodology, we will study the structural and functional implications of all the acetylation sites in glycolytic enzymes. We will also decipher the mechanism by which acetylation is regulated by deacetylases and answer a long standing question – how 18 deacetylases recognise their substrates among thousands of acetylated proteins? The developed methodologies can be applied to a wide range of protein families known to be acetylated, thereby making this study relevant to diverse research fields.
Summary
Synthetic biology is an emerging discipline that offers powerful tools to control and manipulate fundamental processes in living matter. We propose to develop and apply such tools to modify the genetic code of cultured mammalian cells and bacteria with the aim to study the role of lysine acetylation in the regulation of metabolism and in cancer development. Thousands of lysine acetylation sites were recently discovered on non-histone proteins, suggesting that acetylation is a widespread and evolutionarily conserved post translational modification, similar in scope to phosphorylation and ubiquitination. Specifically, it has been found that most of the enzymes of metabolic processes—including glycolysis—are acetylated, implying that acetylation is key regulator of cellular metabolism in general and in glycolysis in particular. The regulation of metabolic pathways is of particular importance to cancer research, as misregulation of metabolic pathways, especially upregulation of glycolysis, is common to most transformed cells and is now considered a new hallmark of cancer. These data raise an immediate question: what is the role of acetylation in the regulation of glycolysis and in the metabolic reprogramming of cancer cells? While current methods rely on mutational analyses, we will genetically encode the incorporation of acetylated lysine and directly measure the functional role of each acetylation site in cancerous and non-cancerous cell lines. Using this methodology, we will study the structural and functional implications of all the acetylation sites in glycolytic enzymes. We will also decipher the mechanism by which acetylation is regulated by deacetylases and answer a long standing question – how 18 deacetylases recognise their substrates among thousands of acetylated proteins? The developed methodologies can be applied to a wide range of protein families known to be acetylated, thereby making this study relevant to diverse research fields.
Max ERC Funding
1 499 375 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym ACTAR TPC
Project Active Target and Time Projection Chamber
Researcher (PI) Gwen Grinyer
Host Institution (HI) GRAND ACCELERATEUR NATIONAL D'IONS LOURDS
Country France
Call Details Starting Grant (StG), PE2, ERC-2013-StG
Summary The active target and time projection chamber (ACTAR TPC) is a novel gas-filled detection system that will permit new studies into the structure and decays of the most exotic nuclei. The use of a gas volume that acts as a sensitive detection medium and as the reaction target itself (an “active target”) offers considerable advantages over traditional nuclear physics detectors and techniques. In high-energy physics, TPC detectors have found profitable applications but their use in nuclear physics has been limited. With the ACTAR TPC design, individual detection pad sizes of 2 mm are the smallest ever attempted in either discipline but is a requirement for high-efficiency and high-resolution nuclear spectroscopy. The corresponding large number of electronic channels (16000 from a surface of only 25×25 cm) requires new developments in high-density electronics and data-acquisition systems that are not yet available in the nuclear physics domain. New experiments in regions of the nuclear chart that cannot be presently contemplated will become feasible with ACTAR TPC.
Summary
The active target and time projection chamber (ACTAR TPC) is a novel gas-filled detection system that will permit new studies into the structure and decays of the most exotic nuclei. The use of a gas volume that acts as a sensitive detection medium and as the reaction target itself (an “active target”) offers considerable advantages over traditional nuclear physics detectors and techniques. In high-energy physics, TPC detectors have found profitable applications but their use in nuclear physics has been limited. With the ACTAR TPC design, individual detection pad sizes of 2 mm are the smallest ever attempted in either discipline but is a requirement for high-efficiency and high-resolution nuclear spectroscopy. The corresponding large number of electronic channels (16000 from a surface of only 25×25 cm) requires new developments in high-density electronics and data-acquisition systems that are not yet available in the nuclear physics domain. New experiments in regions of the nuclear chart that cannot be presently contemplated will become feasible with ACTAR TPC.
Max ERC Funding
1 290 000 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ActiDrops
Project Synthetic Active Droplets Inspired by Life
Researcher (PI) Job BOEKHOVEN
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2019-STG
Summary Active droplets are made of molecular building blocks that are activated and deactivated by a chemical reaction cycle. In the activation, a precursor is converted into a building block for droplets driven by the consumption of fuel. In the deactivation, the building blocks react back to the precursor. In other words, active droplets emerge when fuel is supplied, but decay when fuel is depleted. Theoretical studies show active droplets all evolve to the same size. Another work predicts that the droplets can spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division are pivotal to the functioning of life. If we could engineer these behaviors in synthetic materials, we would obtain a better understanding of active assembly which is directly relevant to biology and the origin of life.
I thus aim to synthesize active droplets and study their life-like properties. Two types of active droplets will be investigated; one type based on oil-molecules that phase separate in water, and one type based on cationic peptides in a complex coacervate with RNA. My team will develop reaction cycles that drive the droplet formation, thereby making them active. We will study their spontaneous emergence in response to energy, and disappearance when energy is scarce. Moreover, we study their collective behavior, like how they grow into one large droplet, or all converge to the same droplet volume. Finally, we test their division into daughter droplets. Our systematic approach will test how kinetic parameters, like the activation rate, affect the behavior of the droplets.
The results will mark a massive step forward in the engineering of materials with life-like behaviors, which can also serve as experimental models for membrane-less organelles. We expect to elucidate mechanisms that could have played a role in the origin of life. Finally, our findings could form stepping stones towards a synthetic cel.
Summary
Active droplets are made of molecular building blocks that are activated and deactivated by a chemical reaction cycle. In the activation, a precursor is converted into a building block for droplets driven by the consumption of fuel. In the deactivation, the building blocks react back to the precursor. In other words, active droplets emerge when fuel is supplied, but decay when fuel is depleted. Theoretical studies show active droplets all evolve to the same size. Another work predicts that the droplets can spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division are pivotal to the functioning of life. If we could engineer these behaviors in synthetic materials, we would obtain a better understanding of active assembly which is directly relevant to biology and the origin of life.
I thus aim to synthesize active droplets and study their life-like properties. Two types of active droplets will be investigated; one type based on oil-molecules that phase separate in water, and one type based on cationic peptides in a complex coacervate with RNA. My team will develop reaction cycles that drive the droplet formation, thereby making them active. We will study their spontaneous emergence in response to energy, and disappearance when energy is scarce. Moreover, we study their collective behavior, like how they grow into one large droplet, or all converge to the same droplet volume. Finally, we test their division into daughter droplets. Our systematic approach will test how kinetic parameters, like the activation rate, affect the behavior of the droplets.
The results will mark a massive step forward in the engineering of materials with life-like behaviors, which can also serve as experimental models for membrane-less organelles. We expect to elucidate mechanisms that could have played a role in the origin of life. Finally, our findings could form stepping stones towards a synthetic cel.
Max ERC Funding
1 491 350 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
Project acronym ADONIS
Project Attosecond Dynamics On Interfaces and Solids
Researcher (PI) Reinhard Kienberger
Host Institution (HI) Klinik Max Planck Institut für Psychiatrie
Country Germany
Call Details Starting Grant (StG), PE2, ERC-2007-StG
Summary New insight into ever smaller microscopic units of matter as well as in ever faster evolving chemical, physical or atomic processes pushes the frontiers in many fields in science. Pump/probe experiments turned out to be the most direct approach to time-domain investigations of fast-evolving microscopic processes. Accessing atomic and molecular inner-shell processes directly in the time-domain requires a combination of short wavelengths in the few hundred eV range and sub-femtosecond pulse duration. The concept of light-field-controlled XUV photoemission employs an XUV pulse achieved by High-order Harmonic Generation (HHG) as a pump and the light pulse as a probe or vice versa. The basic prerequisite, namely the generation and measurement of isolated sub-femtosecond XUV pulses synchronized to a strong few-cycle light pulse with attosecond precision, opens up a route to time-resolved inner-shell atomic and molecular spectroscopy with present day sources. Studies of attosecond electronic motion (1 as = 10-18 s) in solids and on surfaces and interfaces have until now remained out of reach. The unprecedented time resolution of the aforementioned technique will enable for the first time monitoring of sub-fs dynamics of such systems in the time domain. These dynamics – of electronic excitation, relaxation, and wave packet motion – are of broad scientific interest and pertinent to the development of many modern technologies including semiconductor and molecular electronics, optoelectronics, information processing, photovoltaics, and optical nano-structuring. The purpose of this project is to investigate phenomena like the temporal evolution of direct photoemission, interference effects in resonant photoemission, fast adsorbate-substrate charge transfer, and electronic dynamics in supramolecular assemblies, in a series of experiments in order to overcome the temporal limits of measurements in solid state physics and to better understand processes in microcosm.
Summary
New insight into ever smaller microscopic units of matter as well as in ever faster evolving chemical, physical or atomic processes pushes the frontiers in many fields in science. Pump/probe experiments turned out to be the most direct approach to time-domain investigations of fast-evolving microscopic processes. Accessing atomic and molecular inner-shell processes directly in the time-domain requires a combination of short wavelengths in the few hundred eV range and sub-femtosecond pulse duration. The concept of light-field-controlled XUV photoemission employs an XUV pulse achieved by High-order Harmonic Generation (HHG) as a pump and the light pulse as a probe or vice versa. The basic prerequisite, namely the generation and measurement of isolated sub-femtosecond XUV pulses synchronized to a strong few-cycle light pulse with attosecond precision, opens up a route to time-resolved inner-shell atomic and molecular spectroscopy with present day sources. Studies of attosecond electronic motion (1 as = 10-18 s) in solids and on surfaces and interfaces have until now remained out of reach. The unprecedented time resolution of the aforementioned technique will enable for the first time monitoring of sub-fs dynamics of such systems in the time domain. These dynamics – of electronic excitation, relaxation, and wave packet motion – are of broad scientific interest and pertinent to the development of many modern technologies including semiconductor and molecular electronics, optoelectronics, information processing, photovoltaics, and optical nano-structuring. The purpose of this project is to investigate phenomena like the temporal evolution of direct photoemission, interference effects in resonant photoemission, fast adsorbate-substrate charge transfer, and electronic dynamics in supramolecular assemblies, in a series of experiments in order to overcome the temporal limits of measurements in solid state physics and to better understand processes in microcosm.
Max ERC Funding
1 296 000 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym AGALT
Project Asymptotic Geometric Analysis and Learning Theory
Researcher (PI) Shahar Mendelson
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Country Israel
Call Details Starting Grant (StG), PE1, ERC-2007-StG
Summary In a typical learning problem one tries to approximate an unknown function by a function from a given class using random data, sampled according to an unknown measure. In this project we will be interested in parameters that govern the complexity of a learning problem. It turns out that this complexity is determined by the geometry of certain sets in high dimension that are connected to the given class (random coordinate projections of the class). Thus, one has to understand the structure of these sets as a function of the dimension - which is given by the cardinality of the random sample. The resulting analysis leads to many theoretical questions in Asymptotic Geometric Analysis, Probability (most notably, Empirical Processes Theory) and Combinatorics, which are of independent interest beyond the application to Learning Theory. Our main goal is to describe the role of various complexity parameters involved in a learning problem, to analyze the connections between them and to investigate the way they determine the geometry of the relevant high dimensional sets. Some of the questions we intend to tackle are well known open problems and making progress towards their solution will have a significant theoretical impact. Moreover, this project should lead to a more complete theory of learning and is likely to have some practical impact, for example, in the design of more efficient learning algorithms.
Summary
In a typical learning problem one tries to approximate an unknown function by a function from a given class using random data, sampled according to an unknown measure. In this project we will be interested in parameters that govern the complexity of a learning problem. It turns out that this complexity is determined by the geometry of certain sets in high dimension that are connected to the given class (random coordinate projections of the class). Thus, one has to understand the structure of these sets as a function of the dimension - which is given by the cardinality of the random sample. The resulting analysis leads to many theoretical questions in Asymptotic Geometric Analysis, Probability (most notably, Empirical Processes Theory) and Combinatorics, which are of independent interest beyond the application to Learning Theory. Our main goal is to describe the role of various complexity parameters involved in a learning problem, to analyze the connections between them and to investigate the way they determine the geometry of the relevant high dimensional sets. Some of the questions we intend to tackle are well known open problems and making progress towards their solution will have a significant theoretical impact. Moreover, this project should lead to a more complete theory of learning and is likely to have some practical impact, for example, in the design of more efficient learning algorithms.
Max ERC Funding
750 000 €
Duration
Start date: 2009-03-01, End date: 2014-02-28
Project acronym AgeingStemCellFate
Project The Role of Ectopic Adipocyte Progenitors in Age-related Stem Cell Dysfunction, Systemic Inflammation, and Metabolic Disease
Researcher (PI) Tim Julius Schulz
Host Institution (HI) DEUTSCHES INSTITUT FUER ERNAEHRUNGSFORSCHUNG POTSDAM REHBRUECKE
Country Germany
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Ageing is accompanied by ectopic white adipose tissue depositions in skeletal muscle and other anatomical locations, such as brown adipose tissue and the bone marrow. Ectopic fat accrual contributes to organ dysfunction, systemic insulin resistance, and other perturbations that have been implicated in metabolic diseases.
This research proposal aims to identify the regulatory cues that control the development of ectopic progenitor cells that give rise to this type of fat. It is hypothesized that an age-related dysfunction of the stem cell niche leads to an imbalance between (1) tissue-specific stem cells and (2) fibroblast-like, primarily adipogenic progenitors that reside within many tissues. Novel methodologies that assess stem/progenitor cell characteristics on the single cell level will be combined with animal models of lineage tracing to determine the developmental origin of these adipogenic progenitors and processes that regulate their function.
Notch signalling is a key signalling pathway that relies on direct physical interaction to control stem cell fate. It is proposed that impaired Notch activity contributes to the phenotypical shift of precursor cell distribution in aged tissues.
Lastly, the role of the stem cell niche in ectopic adipocyte progenitor formation will be analyzed. External signals originating from the surrounding niche cells regulate the developmental fate of stem cells. Secreted factors and their role in the formation of ectopic adipocyte precursors during senescence will be identified using a combination of biochemical and systems biology approaches.
Accomplishment of these studies will help to understand the basic processes of stem cell ageing and identify mechanisms of age-related functional decline in tissue regeneration. By targeting the population of tissue-resident adipogenic progenitor cells, therapeutic strategies could be developed to counteract metabolic complications associated with the ageing process.
Summary
Ageing is accompanied by ectopic white adipose tissue depositions in skeletal muscle and other anatomical locations, such as brown adipose tissue and the bone marrow. Ectopic fat accrual contributes to organ dysfunction, systemic insulin resistance, and other perturbations that have been implicated in metabolic diseases.
This research proposal aims to identify the regulatory cues that control the development of ectopic progenitor cells that give rise to this type of fat. It is hypothesized that an age-related dysfunction of the stem cell niche leads to an imbalance between (1) tissue-specific stem cells and (2) fibroblast-like, primarily adipogenic progenitors that reside within many tissues. Novel methodologies that assess stem/progenitor cell characteristics on the single cell level will be combined with animal models of lineage tracing to determine the developmental origin of these adipogenic progenitors and processes that regulate their function.
Notch signalling is a key signalling pathway that relies on direct physical interaction to control stem cell fate. It is proposed that impaired Notch activity contributes to the phenotypical shift of precursor cell distribution in aged tissues.
Lastly, the role of the stem cell niche in ectopic adipocyte progenitor formation will be analyzed. External signals originating from the surrounding niche cells regulate the developmental fate of stem cells. Secreted factors and their role in the formation of ectopic adipocyte precursors during senescence will be identified using a combination of biochemical and systems biology approaches.
Accomplishment of these studies will help to understand the basic processes of stem cell ageing and identify mechanisms of age-related functional decline in tissue regeneration. By targeting the population of tissue-resident adipogenic progenitor cells, therapeutic strategies could be developed to counteract metabolic complications associated with the ageing process.
Max ERC Funding
1 496 444 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym AlCHIMIE
Project From hydrocarbons to original chiral building blocks: new solutions for sustainable & asymmetric CH functionalization of alkanes
Researcher (PI) Joanna WENCEL-DELORD
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Starting Grant (StG), PE5, ERC-2020-STG
Summary Over the last decade, major environmental concerns, a growing worldwide population and an increasing energy demand, combined with the depletion of natural resources, have become crucial issues. Sustainable chemistry-ably to supply society with key chemical products in an eco-compatible manner-has therefore rapidly become an urgent challenge. The AlCHiMIE aims at providing new solutions towards this important defy by developing a set of complementary approaches to convert hydrocarbons, the simplest feedstock, into high value-added chiral alkanes-essential building blocks for medicinal chemistry. Two approaches are thus proposed. First, undirected, metal-free functionalization of hydrocarbons will be achieved by means of regio- and stereo-selective hypervalent bromine-enabled C-H functionalization. This unique reactivity will be attaint by discovering a largely uncharted, yet extremely appealing field of bromanes. The second approach concerns earth-abundant metal-catalyzed C(sp3)-H activation. To obviate the inherent difficulties of this field, namely the low reactivity of alkanes and arduous stereoinduction while using 3d metals, I will develop bifunctional ligands for Co- and Ni-catalyzed C-H activation. In addition to the role of metal coordination, these ligands featuring a second coordinating motif, will enhance the metallation event and will promote the substrate’s activation, thus unlocking the door towards previously inaccessible modes of reactivity. The combination of both strategies will allow unprecedented hydrocarbon valorization by means of undirected, hypervalent bromine-enabled first functionalization followed by exploiting the newly installed coordinating motif to promote directed, asymmetric Co- and Ni-catalyzed C-H activations. Finally, I will also endeavor in establishing new reactivities arising from the application of diversely substituted hypervalent bromines as coupling partners in enantioselective Co- and Ni-catalyzed C-H activations.
Summary
Over the last decade, major environmental concerns, a growing worldwide population and an increasing energy demand, combined with the depletion of natural resources, have become crucial issues. Sustainable chemistry-ably to supply society with key chemical products in an eco-compatible manner-has therefore rapidly become an urgent challenge. The AlCHiMIE aims at providing new solutions towards this important defy by developing a set of complementary approaches to convert hydrocarbons, the simplest feedstock, into high value-added chiral alkanes-essential building blocks for medicinal chemistry. Two approaches are thus proposed. First, undirected, metal-free functionalization of hydrocarbons will be achieved by means of regio- and stereo-selective hypervalent bromine-enabled C-H functionalization. This unique reactivity will be attaint by discovering a largely uncharted, yet extremely appealing field of bromanes. The second approach concerns earth-abundant metal-catalyzed C(sp3)-H activation. To obviate the inherent difficulties of this field, namely the low reactivity of alkanes and arduous stereoinduction while using 3d metals, I will develop bifunctional ligands for Co- and Ni-catalyzed C-H activation. In addition to the role of metal coordination, these ligands featuring a second coordinating motif, will enhance the metallation event and will promote the substrate’s activation, thus unlocking the door towards previously inaccessible modes of reactivity. The combination of both strategies will allow unprecedented hydrocarbon valorization by means of undirected, hypervalent bromine-enabled first functionalization followed by exploiting the newly installed coordinating motif to promote directed, asymmetric Co- and Ni-catalyzed C-H activations. Finally, I will also endeavor in establishing new reactivities arising from the application of diversely substituted hypervalent bromines as coupling partners in enantioselective Co- and Ni-catalyzed C-H activations.
Max ERC Funding
1 499 800 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
Project acronym AlgTateGro
Project Constructing line bundles on algebraic varieties -- around conjectures of Tate and Grothendieck
Researcher (PI) Francois CHARLES
Host Institution (HI) UNIVERSITE PARIS-SACLAY
Country France
Call Details Starting Grant (StG), PE1, ERC-2016-STG
Summary The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences.
My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.
Summary
The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences.
My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.
Max ERC Funding
1 222 329 €
Duration
Start date: 2016-12-01, End date: 2021-11-30
Project acronym Allosteric-CRISPR
Project Computational Investigations of Allostery between Proteins and Nucleic Acids in CRISPR-Cas9
Researcher (PI) Giulia Palermo
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), PE4, ERC-2020-STG
Summary Allostery is a fundamental property of proteins, which regulates biochemical information transfer between spatially distant sites. Many emerging allosteric targets are large protein/nucleic acid complexes responsible for genome editing and regulation, whose underlying signaling remains poorly understood. Here, we focus on CRISPR-Cas9, a large nucleoprotein complex widely employed as a genome editing tool with enormous promises for medicine and biotechnology. In this system, an intricate allosteric signaling is suggested to span the multi-domain Cas9 protein and its associated nucleic acids, controlling the system’s function and specificity. However, in spite of extensive experimental characterization, the molecular basis for this allosteric response are largely unknown, hampering also efficient engineering for improving its genome editing capability. Allosteric-CRISPR will investigate the allosteric regulation in CRISPR-Cas9 by introducing a novel synergistic approach. This will implement the combination of state-of-the-art theoretical methods, including enhanced and multiscale approaches based on classical and ab-initio methods, with network models derived from graph theory and novel centrality analyses that are emerging as powerful to investigate allostery. This will create an innovative protocol that will enable determining the allosteric network of communication over multiple timescales, as well as the relation between allostery and catalysis, which remains unaddressed through classical approaches. This novel way to describe allostery can impact future studies of large nucleoprotein complexes, including newly discovered CRISPR systems, which are governed by similar allosteric rules and hold tremendous potential for genome editing. Finally, by delivering fundamental knowledge on the basic mechanisms underlying genome editing, Allosteric-CRISPR will help the design of improved genome editing tools, impacting their application across the field of life sciences.
Summary
Allostery is a fundamental property of proteins, which regulates biochemical information transfer between spatially distant sites. Many emerging allosteric targets are large protein/nucleic acid complexes responsible for genome editing and regulation, whose underlying signaling remains poorly understood. Here, we focus on CRISPR-Cas9, a large nucleoprotein complex widely employed as a genome editing tool with enormous promises for medicine and biotechnology. In this system, an intricate allosteric signaling is suggested to span the multi-domain Cas9 protein and its associated nucleic acids, controlling the system’s function and specificity. However, in spite of extensive experimental characterization, the molecular basis for this allosteric response are largely unknown, hampering also efficient engineering for improving its genome editing capability. Allosteric-CRISPR will investigate the allosteric regulation in CRISPR-Cas9 by introducing a novel synergistic approach. This will implement the combination of state-of-the-art theoretical methods, including enhanced and multiscale approaches based on classical and ab-initio methods, with network models derived from graph theory and novel centrality analyses that are emerging as powerful to investigate allostery. This will create an innovative protocol that will enable determining the allosteric network of communication over multiple timescales, as well as the relation between allostery and catalysis, which remains unaddressed through classical approaches. This novel way to describe allostery can impact future studies of large nucleoprotein complexes, including newly discovered CRISPR systems, which are governed by similar allosteric rules and hold tremendous potential for genome editing. Finally, by delivering fundamental knowledge on the basic mechanisms underlying genome editing, Allosteric-CRISPR will help the design of improved genome editing tools, impacting their application across the field of life sciences.
Max ERC Funding
1 399 632 €
Duration
Start date: 2021-08-01, End date: 2026-07-31