Project acronym 2D-4-CO2
Project DESIGNING 2D NANOSHEETS FOR CO2 REDUCTION AND INTEGRATION INTO vdW HETEROSTRUCTURES FOR ARTIFICIAL PHOTOSYNTHESIS
Researcher (PI) Damien VOIRY
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary CO2 reduction reaction (CO2RR) holds great promise for conversion of the green-house gas carbon dioxide into chemical fuels. The absence of catalytic materials demonstrating high performance and high selectivity currently hampers practical demonstration. CO2RR is also limited by the low solubility of CO2 in the electrolyte solution and therefore electrocatalytic reactions in gas phase using gas diffusion electrodes would be preferred. 2D materials have recently emerged as a novel class of electrocatalytic materials thanks to their rich structures and electronic properties. The synthesis of novel 2D catalysts and their implementation into photocatalytic systems would be a major step towards the development of devices for storing solar energy in the form of chemical fuels. With 2D-4-CO2, I propose to: 1) develop novel class of CO2RR catalysts based on conducting 2D nanosheets and 2) demonstrate photocatalytic conversion of CO2 into chemical fuels using structure engineered gas diffusion electrodes made of 2D conducting catalysts. To reach this goal, the first objective of 2D-4-CO2 is to provide guidelines for the development of novel cutting-edge 2D catalysts towards CO2 conversion into chemical fuel. This will be possible by using a multidisciplinary approach based on 2D materials engineering, advanced methods of characterization and novel designs of gas diffusion electrodes for the reduction of CO2 in gas phase. The second objective is to develop practical photocatalytic systems using van der Waals (vdW) heterostructures for the efficient conversion of CO2 into chemical fuels. vdW heterostructures will consist in rational designs of 2D materials and 2D-like materials deposited by atomic layer deposition in order to achieve highly efficient light conversion and prolonged stability. This project will not only enable a deeper understanding of the CO2RR but it will also provide practical strategies for large-scale application of CO2RR for solar fuel production.
Summary
CO2 reduction reaction (CO2RR) holds great promise for conversion of the green-house gas carbon dioxide into chemical fuels. The absence of catalytic materials demonstrating high performance and high selectivity currently hampers practical demonstration. CO2RR is also limited by the low solubility of CO2 in the electrolyte solution and therefore electrocatalytic reactions in gas phase using gas diffusion electrodes would be preferred. 2D materials have recently emerged as a novel class of electrocatalytic materials thanks to their rich structures and electronic properties. The synthesis of novel 2D catalysts and their implementation into photocatalytic systems would be a major step towards the development of devices for storing solar energy in the form of chemical fuels. With 2D-4-CO2, I propose to: 1) develop novel class of CO2RR catalysts based on conducting 2D nanosheets and 2) demonstrate photocatalytic conversion of CO2 into chemical fuels using structure engineered gas diffusion electrodes made of 2D conducting catalysts. To reach this goal, the first objective of 2D-4-CO2 is to provide guidelines for the development of novel cutting-edge 2D catalysts towards CO2 conversion into chemical fuel. This will be possible by using a multidisciplinary approach based on 2D materials engineering, advanced methods of characterization and novel designs of gas diffusion electrodes for the reduction of CO2 in gas phase. The second objective is to develop practical photocatalytic systems using van der Waals (vdW) heterostructures for the efficient conversion of CO2 into chemical fuels. vdW heterostructures will consist in rational designs of 2D materials and 2D-like materials deposited by atomic layer deposition in order to achieve highly efficient light conversion and prolonged stability. This project will not only enable a deeper understanding of the CO2RR but it will also provide practical strategies for large-scale application of CO2RR for solar fuel production.
Max ERC Funding
1 499 931 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym 3D-FABRIC
Project 3D Flow Analysis in Bijels Reconfigured for Interfacial Catalysis
Researcher (PI) Martin F. HAASE
Host Institution (HI) UNIVERSITEIT UTRECHT
Country Netherlands
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Summary
The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Max ERC Funding
1 905 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym 3D-FIREFLUC
Project Taming the particle transport in magnetized plasmas via perturbative fields
Researcher (PI) Eleonora VIEZZER
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Country Spain
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary Wave-particle interactions are ubiquitous in nature and play a fundamental role in astrophysical and fusion plasmas. In solar plasmas, magnetohydrodynamic (MHD) fluctuations are thought to be responsible for the heating of the solar corona and the generation of the solar wind. In magnetically confined fusion (MCF) devices, enhanced particle transport induced by MHD fluctuations can deteriorate the plasma confinement, and also endanger the device integrity. MCF devices are an ideal testbed to verify current models and develop mitigation / protection techniques.
The proposed project paves the way for providing active control techniques to tame the MHD induced particle transport in a fusion plasma. A solid understanding of the interaction between energetic particles and MHD instabilities in the presence of electric fields and plasma currents is required to develop such techniques. I will pursue this goal through innovative diagnosis techniques with unprecedented spatio-temporal resolution. Combined with state-of-the-art hybrid MHD codes, a deep insight into the underlying physics mechanism will be gained. The outcome of this research project will have a major impact for next-step MCF devices as I will provide ground-breaking control techniques for mitigating MHD induced particle transport in magnetized plasmas.
The project consists of 3 research lines which follow a bottom-up approach:
(1) Cutting-edge instrumentation, aiming at the new generation of energetic particle and edge current diagnostics.
(2) Unravel the dynamics of energetic particles, electric fields, edge currents and MHD fluctuations.
(3) From lab to space weather: The developed models will revolutionize our understanding of the observed particle acceleration and transport in the solar corona.
Based on this approach, the project represents a gateway between the fusion, astrophysics and space communities opening new avenues for a common basic understanding.
Summary
Wave-particle interactions are ubiquitous in nature and play a fundamental role in astrophysical and fusion plasmas. In solar plasmas, magnetohydrodynamic (MHD) fluctuations are thought to be responsible for the heating of the solar corona and the generation of the solar wind. In magnetically confined fusion (MCF) devices, enhanced particle transport induced by MHD fluctuations can deteriorate the plasma confinement, and also endanger the device integrity. MCF devices are an ideal testbed to verify current models and develop mitigation / protection techniques.
The proposed project paves the way for providing active control techniques to tame the MHD induced particle transport in a fusion plasma. A solid understanding of the interaction between energetic particles and MHD instabilities in the presence of electric fields and plasma currents is required to develop such techniques. I will pursue this goal through innovative diagnosis techniques with unprecedented spatio-temporal resolution. Combined with state-of-the-art hybrid MHD codes, a deep insight into the underlying physics mechanism will be gained. The outcome of this research project will have a major impact for next-step MCF devices as I will provide ground-breaking control techniques for mitigating MHD induced particle transport in magnetized plasmas.
The project consists of 3 research lines which follow a bottom-up approach:
(1) Cutting-edge instrumentation, aiming at the new generation of energetic particle and edge current diagnostics.
(2) Unravel the dynamics of energetic particles, electric fields, edge currents and MHD fluctuations.
(3) From lab to space weather: The developed models will revolutionize our understanding of the observed particle acceleration and transport in the solar corona.
Based on this approach, the project represents a gateway between the fusion, astrophysics and space communities opening new avenues for a common basic understanding.
Max ERC Funding
1 512 250 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym 3DBIOLUNG
Project Bioengineering lung tissue using extracellular matrix based 3D bioprinting
Researcher (PI) Darcy WAGNER
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Chronic lung diseases are increasing in prevalence with over 65 million patients worldwide. Lung transplantation remains the only potential option at end-stage disease. Around 4000 patients receive lung transplants annually with more awaiting transplantation, including 1000 patients in Europe. New options to increase available tissue for lung transplantation are desperately needed.
An exciting new research area focuses on generating lung tissue ex vivo using bioengineering approaches. Scaffolds can be generated from synthetic or biologically-derived (acellular) materials, seeded with cells and grown in a bioreactor prior to transplantation. Ideally, scaffolds would be seeded with cells derived from the transplant recipient, thus obviating the need for long-term immunosuppression. However, functional regeneration has yet to be achieved. New advances in 3D printing and 3D bioprinting (when cells are printed) indicate that this once thought of science-fiction concept might finally be mature enough for complex tissues, including lung. 3D bioprinting addresses a number of concerns identified in previous approaches, such as a) patient heterogeneity in acellular human scaffolds, b) anatomical differences in xenogeneic sources, c) lack of biological cues on synthetic materials and d) difficulty in manufacturing the complex lung architecture. 3D bioprinting could be a reproducible, scalable, and controllable approach for generating functional lung tissue.
The aim of this proposal is to use custom 3D bioprinters to generate constructs mimicking lung tissue using an innovative approach combining primary cells, the engineering reproducibility of synthetic materials, and the biologically conductive properties of acellular lung (hybrid). We will 3D bioprint hybrid murine and human lung tissue models and test gas exchange, angiogenesis and in vivo immune responses. This proposal will be a critical first step in demonstrating feasibility of 3D bioprinting lung tissue.
Summary
Chronic lung diseases are increasing in prevalence with over 65 million patients worldwide. Lung transplantation remains the only potential option at end-stage disease. Around 4000 patients receive lung transplants annually with more awaiting transplantation, including 1000 patients in Europe. New options to increase available tissue for lung transplantation are desperately needed.
An exciting new research area focuses on generating lung tissue ex vivo using bioengineering approaches. Scaffolds can be generated from synthetic or biologically-derived (acellular) materials, seeded with cells and grown in a bioreactor prior to transplantation. Ideally, scaffolds would be seeded with cells derived from the transplant recipient, thus obviating the need for long-term immunosuppression. However, functional regeneration has yet to be achieved. New advances in 3D printing and 3D bioprinting (when cells are printed) indicate that this once thought of science-fiction concept might finally be mature enough for complex tissues, including lung. 3D bioprinting addresses a number of concerns identified in previous approaches, such as a) patient heterogeneity in acellular human scaffolds, b) anatomical differences in xenogeneic sources, c) lack of biological cues on synthetic materials and d) difficulty in manufacturing the complex lung architecture. 3D bioprinting could be a reproducible, scalable, and controllable approach for generating functional lung tissue.
The aim of this proposal is to use custom 3D bioprinters to generate constructs mimicking lung tissue using an innovative approach combining primary cells, the engineering reproducibility of synthetic materials, and the biologically conductive properties of acellular lung (hybrid). We will 3D bioprint hybrid murine and human lung tissue models and test gas exchange, angiogenesis and in vivo immune responses. This proposal will be a critical first step in demonstrating feasibility of 3D bioprinting lung tissue.
Max ERC Funding
1 499 975 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ABDESIGN
Project Computational design of novel protein function in antibodies
Researcher (PI) Sarel-Jacob Fleishman
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Country Israel
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary We propose to elucidate the structural design principles of naturally occurring antibody complementarity-determining regions (CDRs) and to computationally design novel antibody functions. Antibodies represent the most versatile known system for molecular recognition. Research has yielded many insights into antibody design principles and promising biotechnological and pharmaceutical applications. Still, our understanding of how CDRs encode specific loop conformations lags far behind our understanding of structure-function relationships in non-immunological scaffolds. Thus, design of antibodies from first principles has not been demonstrated. We propose a computational-experimental strategy to address this challenge. We will: (a) characterize the design principles and sequence elements that rigidify antibody CDRs. Natural antibody loops will be subjected to computational modeling, crystallography, and a combined in vitro evolution and deep-sequencing approach to isolate sequence features that rigidify loop backbones; (b) develop a novel computational-design strategy, which uses the >1000 solved structures of antibodies deposited in structure databases to realistically model CDRs and design them to recognize proteins that have not been co-crystallized with antibodies. For example, we will design novel antibodies targeting insulin, for which clinically useful diagnostics are needed. By accessing much larger sequence/structure spaces than are available to natural immune-system repertoires and experimental methods, computational antibody design could produce higher-specificity and higher-affinity binders, even to challenging targets; and (c) develop new strategies to program conformational change in CDRs, generating, e.g., the first allosteric antibodies. These will allow targeting, in principle, of any molecule, potentially revolutionizing how antibodies are generated for research and medicine, providing new insights on the design principles of protein functional sites.
Summary
We propose to elucidate the structural design principles of naturally occurring antibody complementarity-determining regions (CDRs) and to computationally design novel antibody functions. Antibodies represent the most versatile known system for molecular recognition. Research has yielded many insights into antibody design principles and promising biotechnological and pharmaceutical applications. Still, our understanding of how CDRs encode specific loop conformations lags far behind our understanding of structure-function relationships in non-immunological scaffolds. Thus, design of antibodies from first principles has not been demonstrated. We propose a computational-experimental strategy to address this challenge. We will: (a) characterize the design principles and sequence elements that rigidify antibody CDRs. Natural antibody loops will be subjected to computational modeling, crystallography, and a combined in vitro evolution and deep-sequencing approach to isolate sequence features that rigidify loop backbones; (b) develop a novel computational-design strategy, which uses the >1000 solved structures of antibodies deposited in structure databases to realistically model CDRs and design them to recognize proteins that have not been co-crystallized with antibodies. For example, we will design novel antibodies targeting insulin, for which clinically useful diagnostics are needed. By accessing much larger sequence/structure spaces than are available to natural immune-system repertoires and experimental methods, computational antibody design could produce higher-specificity and higher-affinity binders, even to challenging targets; and (c) develop new strategies to program conformational change in CDRs, generating, e.g., the first allosteric antibodies. These will allow targeting, in principle, of any molecule, potentially revolutionizing how antibodies are generated for research and medicine, providing new insights on the design principles of protein functional sites.
Max ERC Funding
1 499 930 €
Duration
Start date: 2013-09-01, End date: 2018-08-31
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 ANTI-ATOM
Project Many-body theory of antimatter interactions with atoms, molecules and condensed matter
Researcher (PI) Dermot GREEN
Host Institution (HI) THE QUEEN'S UNIVERSITY OF BELFAST
Country United Kingdom
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary The ability of positrons to annihilate with electrons, producing characteristic gamma rays, gives them important use in medicine via positron-emission tomography (PET), diagnostics of industrially-important materials, and in elucidating astrophysical phenomena. Moreover, the fundamental interactions of positrons and positronium (Ps) with atoms, molecules and condensed matter are currently under intensive study in numerous international laboratories, to illuminate collision phenomena and perform precision tests of fundamental laws.
Proper interpretation and development of these costly and difficult experiments requires accurate calculations of low-energy positron and Ps interactions with normal matter. These systems, however, involve strong correlations, e.g., polarisation of the atom and virtual-Ps formation (where an atomic electron tunnels to the positron): they significantly effect positron- and Ps-atom/molecule interactions, e.g., enhancing annihilation rates by many orders of magnitude, and making the accurate description of these systems a challenging many-body problem. Current theoretical capability lags severely behind that of experiment. Major theoretical and computational developments are required to bridge the gap.
One powerful method, which accounts for the correlations in a natural, transparent and systematic way, is many-body theory (MBT). Building on my expertise in the field, I propose to develop new MBT to deliver unique and unrivalled capability in theory and computation of low-energy positron and Ps interactions with atoms, molecules, and condensed matter. The ambitious programme will provide the basic understanding required to interpret and develop the fundamental experiments, antimatter-based materials science techniques, and wider technologies, e.g., (PET), and more broadly, potentially revolutionary and generally applicable computational methodologies that promise to define a new level of high-precision in atomic-MBT calculations.
Summary
The ability of positrons to annihilate with electrons, producing characteristic gamma rays, gives them important use in medicine via positron-emission tomography (PET), diagnostics of industrially-important materials, and in elucidating astrophysical phenomena. Moreover, the fundamental interactions of positrons and positronium (Ps) with atoms, molecules and condensed matter are currently under intensive study in numerous international laboratories, to illuminate collision phenomena and perform precision tests of fundamental laws.
Proper interpretation and development of these costly and difficult experiments requires accurate calculations of low-energy positron and Ps interactions with normal matter. These systems, however, involve strong correlations, e.g., polarisation of the atom and virtual-Ps formation (where an atomic electron tunnels to the positron): they significantly effect positron- and Ps-atom/molecule interactions, e.g., enhancing annihilation rates by many orders of magnitude, and making the accurate description of these systems a challenging many-body problem. Current theoretical capability lags severely behind that of experiment. Major theoretical and computational developments are required to bridge the gap.
One powerful method, which accounts for the correlations in a natural, transparent and systematic way, is many-body theory (MBT). Building on my expertise in the field, I propose to develop new MBT to deliver unique and unrivalled capability in theory and computation of low-energy positron and Ps interactions with atoms, molecules, and condensed matter. The ambitious programme will provide the basic understanding required to interpret and develop the fundamental experiments, antimatter-based materials science techniques, and wider technologies, e.g., (PET), and more broadly, potentially revolutionary and generally applicable computational methodologies that promise to define a new level of high-precision in atomic-MBT calculations.
Max ERC Funding
1 318 419 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym ANTIVIRNA
Project Structural and mechanistic studies of RNA-guided and RNA-targeting antiviral defense pathways
Researcher (PI) Martin Jinek
Host Institution (HI) University of Zurich
Country Switzerland
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary The evolutionary pressures exerted by viruses on their host cells constitute a major force that drives the evolution of cellular antiviral mechanisms. The proposed research is motivated by our interest in the roles of protein-RNA interactions in both prokaryotic and eukaryotic antiviral pathways and will proceed in two directions. The first project stems from our current work on the CRISPR pathway, a recently discovered RNA-guided adaptive defense mechanism in bacteria and archaea that silences mobile genetic elements such as viruses (bacteriophages) and plasmids. CRISPR systems rely on short RNAs (crRNAs) that associate with CRISPR-associated (Cas) proteins and function as sequence-specific guides in the detection and destruction of invading nucleic acids. To obtain molecular insights into the mechanisms of crRNA-guided interference, we will pursue structural and functional studies of DNA-targeting ribonuceoprotein complexes from type II and III CRISPR systems. Our work will shed light on the function of these systems in microbial pathogenesis and provide a framework for the informed engineering of RNA-guided gene targeting technologies. The second proposed research direction centres on RNA-targeting antiviral strategies employed by the human innate immune system. Here, our work will focus on structural studies of major interferon-induced effector proteins, initially examining the allosteric activation mechanism of RNase L and subsequently focusing on other antiviral nucleases and RNA helicases, as well as mechanisms by which RNA viruses evade the innate immune response of the host. In our investigations, we plan to approach these questions using an integrated strategy combining structural biology, biochemistry and biophysics with cell-based functional studies. Together, our studies will provide fundamental molecular insights into RNA-centred antiviral mechanisms and their impact on human health and disease.
Summary
The evolutionary pressures exerted by viruses on their host cells constitute a major force that drives the evolution of cellular antiviral mechanisms. The proposed research is motivated by our interest in the roles of protein-RNA interactions in both prokaryotic and eukaryotic antiviral pathways and will proceed in two directions. The first project stems from our current work on the CRISPR pathway, a recently discovered RNA-guided adaptive defense mechanism in bacteria and archaea that silences mobile genetic elements such as viruses (bacteriophages) and plasmids. CRISPR systems rely on short RNAs (crRNAs) that associate with CRISPR-associated (Cas) proteins and function as sequence-specific guides in the detection and destruction of invading nucleic acids. To obtain molecular insights into the mechanisms of crRNA-guided interference, we will pursue structural and functional studies of DNA-targeting ribonuceoprotein complexes from type II and III CRISPR systems. Our work will shed light on the function of these systems in microbial pathogenesis and provide a framework for the informed engineering of RNA-guided gene targeting technologies. The second proposed research direction centres on RNA-targeting antiviral strategies employed by the human innate immune system. Here, our work will focus on structural studies of major interferon-induced effector proteins, initially examining the allosteric activation mechanism of RNase L and subsequently focusing on other antiviral nucleases and RNA helicases, as well as mechanisms by which RNA viruses evade the innate immune response of the host. In our investigations, we plan to approach these questions using an integrated strategy combining structural biology, biochemistry and biophysics with cell-based functional studies. Together, our studies will provide fundamental molecular insights into RNA-centred antiviral mechanisms and their impact on human health and disease.
Max ERC Funding
1 467 180 €
Duration
Start date: 2013-11-01, End date: 2018-10-31
Project acronym ANYON
Project Engineering and exploring anyonic quantum gases
Researcher (PI) Christof WEITENBERG
Host Institution (HI) UNIVERSITAET HAMBURG
Country Germany
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms.
Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics.
Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas.
In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms.
Summary
This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms.
Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics.
Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas.
In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms.
Max ERC Funding
1 497 500 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym assemblyNMR
Project 3D structures of bacterial supramolecular assemblies by solid-state NMR
Researcher (PI) Adam Lange
Host Institution (HI) FORSCHUNGSVERBUND BERLIN EV
Country Germany
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary Supramolecular assemblies – formed by the self-assembly of hundreds of protein subunits – are part of bacterial nanomachines involved in key cellular processes. Important examples in pathogenic bacteria are pili and type 3 secretion systems (T3SS) that mediate adhesion to host cells and injection of virulence proteins. Structure determination at atomic resolution of such assemblies by standard techniques such as X-ray crystallography or solution NMR is severely limited: Intact T3SSs or pili cannot be crystallized and are also inherently insoluble. Cryo-electron microscopy techniques have recently made it possible to obtain low- and medium-resolution models, but atomic details have not been accessible at the resolution obtained in these studies, leading sometimes to inaccurate models.
I propose to use solid-state NMR (ssNMR) to fill this knowledge-gap. I could recently show that ssNMR on in vitro preparations of Salmonella T3SS needles constitutes a powerful approach to study the structure of this virulence factor. Our integrated approach also included results from electron microscopy and modeling as well as in vivo assays (Loquet et al., Nature 2012). This is the foundation of this application. I propose to extend ssNMR methodology to tackle the structures of even larger or more complex homo-oligomeric assemblies with up to 200 residues per monomeric subunit. We will apply such techniques to address the currently unknown 3D structures of type I pili and cytoskeletal bactofilin filaments. Furthermore, I want to develop strategies to directly study assemblies in a native-like setting. As a first application, I will study the 3D structure of T3SS needles when they are complemented with intact T3SSs purified from Salmonella or Shigella. The ultimate goal of this proposal is to establish ssNMR as a generally applicable method that allows solving the currently unknown structures of bacterial supramolecular assemblies at atomic resolution.
Summary
Supramolecular assemblies – formed by the self-assembly of hundreds of protein subunits – are part of bacterial nanomachines involved in key cellular processes. Important examples in pathogenic bacteria are pili and type 3 secretion systems (T3SS) that mediate adhesion to host cells and injection of virulence proteins. Structure determination at atomic resolution of such assemblies by standard techniques such as X-ray crystallography or solution NMR is severely limited: Intact T3SSs or pili cannot be crystallized and are also inherently insoluble. Cryo-electron microscopy techniques have recently made it possible to obtain low- and medium-resolution models, but atomic details have not been accessible at the resolution obtained in these studies, leading sometimes to inaccurate models.
I propose to use solid-state NMR (ssNMR) to fill this knowledge-gap. I could recently show that ssNMR on in vitro preparations of Salmonella T3SS needles constitutes a powerful approach to study the structure of this virulence factor. Our integrated approach also included results from electron microscopy and modeling as well as in vivo assays (Loquet et al., Nature 2012). This is the foundation of this application. I propose to extend ssNMR methodology to tackle the structures of even larger or more complex homo-oligomeric assemblies with up to 200 residues per monomeric subunit. We will apply such techniques to address the currently unknown 3D structures of type I pili and cytoskeletal bactofilin filaments. Furthermore, I want to develop strategies to directly study assemblies in a native-like setting. As a first application, I will study the 3D structure of T3SS needles when they are complemented with intact T3SSs purified from Salmonella or Shigella. The ultimate goal of this proposal is to establish ssNMR as a generally applicable method that allows solving the currently unknown structures of bacterial supramolecular assemblies at atomic resolution.
Max ERC Funding
1 456 000 €
Duration
Start date: 2014-05-01, End date: 2019-04-30