Project acronym 3D-BioMat
Project Deciphering biomineralization mechanisms through 3D explorations of mesoscale crystalline structure in calcareous biomaterials
Researcher (PI) VIRGINIE CHAMARD
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Consolidator Grant (CoG), PE3, ERC-2016-COG
Summary The fundamental 3D-BioMat project aims at providing a biomineralization model to explain the formation of microscopic calcareous single-crystals produced by living organisms. Although these crystals present a wide variety of shapes, associated to various organic materials, the observation of a nanoscale granular structure common to almost all calcareous crystallizing organisms, associated to an extended crystalline coherence, underlies a generic biomineralization and assembly process. A key to building realistic scenarios of biomineralization is to reveal the crystalline architecture, at the mesoscale, (i. e., over a few granules), which none of the existing nano-characterization tools is able to provide.
3D-BioMat is based on the recognized PI’s expertise in the field of synchrotron coherent x-ray diffraction microscopy. It will extend the PI’s disruptive pioneering microscopy formalism, towards an innovative high-throughput approach able at giving access to the 3D mesoscale image of the crystalline properties (crystal-line coherence, crystal plane tilts and strains) with the required flexibility, nanoscale resolution, and non-invasiveness.
This achievement will be used to timely reveal the generics of the mesoscale crystalline structure through the pioneering explorations of a vast variety of crystalline biominerals produced by the famous Pinctada mar-garitifera oyster shell, and thereby build a realistic biomineralization scenario.
The inferred biomineralization pathways, including both physico-chemical pathways and biological controls, will ultimately be validated by comparing the mesoscale structures produced by biomimetic samples with the biogenic ones. Beyond deciphering one of the most intriguing questions of material nanosciences, 3D-BioMat may contribute to new climate models, pave the way for new routes in material synthesis and supply answers to the pearl-culture calcification problems.
Summary
The fundamental 3D-BioMat project aims at providing a biomineralization model to explain the formation of microscopic calcareous single-crystals produced by living organisms. Although these crystals present a wide variety of shapes, associated to various organic materials, the observation of a nanoscale granular structure common to almost all calcareous crystallizing organisms, associated to an extended crystalline coherence, underlies a generic biomineralization and assembly process. A key to building realistic scenarios of biomineralization is to reveal the crystalline architecture, at the mesoscale, (i. e., over a few granules), which none of the existing nano-characterization tools is able to provide.
3D-BioMat is based on the recognized PI’s expertise in the field of synchrotron coherent x-ray diffraction microscopy. It will extend the PI’s disruptive pioneering microscopy formalism, towards an innovative high-throughput approach able at giving access to the 3D mesoscale image of the crystalline properties (crystal-line coherence, crystal plane tilts and strains) with the required flexibility, nanoscale resolution, and non-invasiveness.
This achievement will be used to timely reveal the generics of the mesoscale crystalline structure through the pioneering explorations of a vast variety of crystalline biominerals produced by the famous Pinctada mar-garitifera oyster shell, and thereby build a realistic biomineralization scenario.
The inferred biomineralization pathways, including both physico-chemical pathways and biological controls, will ultimately be validated by comparing the mesoscale structures produced by biomimetic samples with the biogenic ones. Beyond deciphering one of the most intriguing questions of material nanosciences, 3D-BioMat may contribute to new climate models, pave the way for new routes in material synthesis and supply answers to the pearl-culture calcification problems.
Max ERC Funding
1 966 429 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym BACTIN
Project Shaping the bacterial cell wall: the actin-like cytoskeleton, from single molecules to morphogenesis and antimicrobials
Researcher (PI) Rut CARBALLIDO LOPEZ
Host Institution (HI) INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT
Country France
Call Details Consolidator Grant (CoG), LS3, ERC-2017-COG
Summary One of the ultimate goals in cell biology is to understand how cells determine their shape. In bacteria, the cell wall and the actin-like (MreB) cytoskeleton are major determinants of cell shape. As a hallmark of microbial life, the external cell wall is the most conspicuous macromolecule expanding in concert with cell growth and one of the most prominent targets for antibiotics. Despite decades of study, the mechanism of cell wall morphogenesis remains poorly understood. In rod-shaped bacteria, actin-like MreB proteins assemble into disconnected membrane-associated structures (patches) that move processively around the cell periphery and are thought to control shape by spatiotemporally organizing macromolecular machineries that effect sidewall elongation. However, the ultrastructure of MreB assemblies and the mechanistic details underlying their morphogenetic function remain to be elucidated.
The aim of this project is to combine ground-breaking light microscopy and spectroscopy techniques with cutting-edge genetic, biochemical and systems biology approaches available in the model rod-shaped bacterium Bacillus subtilis to elucidate how MreB and cell wall biosynthetic enzymes collectively act to build a cell. Within this context, new features of MreB assemblies will be determined in vivo and in vitro, and a “toolbox” of approaches to determine the modes of action of antibiotics targeting cell wall processes will be developed. Parameters measured by the different approaches will be used to refine a mathematical model aiming to quantitatively describe the features of bacterial cell wall growth. The long-term goals of BActin are to understand general principles of bacterial cell morphogenesis and to provide mechanistic templates and new reporters for the screening of novel antibiotics.
Summary
One of the ultimate goals in cell biology is to understand how cells determine their shape. In bacteria, the cell wall and the actin-like (MreB) cytoskeleton are major determinants of cell shape. As a hallmark of microbial life, the external cell wall is the most conspicuous macromolecule expanding in concert with cell growth and one of the most prominent targets for antibiotics. Despite decades of study, the mechanism of cell wall morphogenesis remains poorly understood. In rod-shaped bacteria, actin-like MreB proteins assemble into disconnected membrane-associated structures (patches) that move processively around the cell periphery and are thought to control shape by spatiotemporally organizing macromolecular machineries that effect sidewall elongation. However, the ultrastructure of MreB assemblies and the mechanistic details underlying their morphogenetic function remain to be elucidated.
The aim of this project is to combine ground-breaking light microscopy and spectroscopy techniques with cutting-edge genetic, biochemical and systems biology approaches available in the model rod-shaped bacterium Bacillus subtilis to elucidate how MreB and cell wall biosynthetic enzymes collectively act to build a cell. Within this context, new features of MreB assemblies will be determined in vivo and in vitro, and a “toolbox” of approaches to determine the modes of action of antibiotics targeting cell wall processes will be developed. Parameters measured by the different approaches will be used to refine a mathematical model aiming to quantitatively describe the features of bacterial cell wall growth. The long-term goals of BActin are to understand general principles of bacterial cell morphogenesis and to provide mechanistic templates and new reporters for the screening of novel antibiotics.
Max ERC Funding
1 902 195 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym BigFastData
Project Charting a New Horizon of Big and Fast Data Analysis through Integrated Algorithm Design
Researcher (PI) Yanlei DIAO
Host Institution (HI) ECOLE POLYTECHNIQUE
Country France
Call Details Consolidator Grant (CoG), PE6, ERC-2016-COG
Summary This proposal addresses a pressing need from emerging big data applications such as genomics and data center monitoring: besides the scale of processing, big data systems must also enable perpetual, low-latency processing for a broad set of analytical tasks, referred to as big and fast data analysis. Today’s technology falls severely short for such needs due to the lack of support of complex analytics with scale, low latency, and strong guarantees of user performance requirements. To bridge the gap, this proposal tackles a grand challenge: “How do we design an algorithmic foundation that enables the development of all necessary pillars of big and fast data analysis?” This proposal considers three pillars:
1) Parallelism: There is a fundamental tension between data parallelism (for scale) and pipeline parallelism (for low latency). We propose new approaches based on intelligent use of memory and workload properties to integrate both forms of parallelism.
2) Analytics: The literature lacks a large body of algorithms for critical order-related analytics to be run under data and pipeline parallelism. We propose new algorithmic frameworks to enable such analytics.
3) Optimization: To run analytics, today's big data systems are best effort only. We transform such systems into a principled optimization framework that suits the new characteristics of big data infrastructure and adapts to meet user performance requirements.
The scale and complexity of the proposed algorithm design makes this project high-risk, at the same time, high-gain: it will lay a solid foundation for big and fast data analysis, enabling a new integrated parallel processing paradigm, algorithms for critical order-related analytics, and a principled optimizer with strong performance guarantees. It will also broadly enable accelerated information discovery in emerging domains such as genomics, as well as economic benefits of early, well-informed decisions and reduced user payments.
Summary
This proposal addresses a pressing need from emerging big data applications such as genomics and data center monitoring: besides the scale of processing, big data systems must also enable perpetual, low-latency processing for a broad set of analytical tasks, referred to as big and fast data analysis. Today’s technology falls severely short for such needs due to the lack of support of complex analytics with scale, low latency, and strong guarantees of user performance requirements. To bridge the gap, this proposal tackles a grand challenge: “How do we design an algorithmic foundation that enables the development of all necessary pillars of big and fast data analysis?” This proposal considers three pillars:
1) Parallelism: There is a fundamental tension between data parallelism (for scale) and pipeline parallelism (for low latency). We propose new approaches based on intelligent use of memory and workload properties to integrate both forms of parallelism.
2) Analytics: The literature lacks a large body of algorithms for critical order-related analytics to be run under data and pipeline parallelism. We propose new algorithmic frameworks to enable such analytics.
3) Optimization: To run analytics, today's big data systems are best effort only. We transform such systems into a principled optimization framework that suits the new characteristics of big data infrastructure and adapts to meet user performance requirements.
The scale and complexity of the proposed algorithm design makes this project high-risk, at the same time, high-gain: it will lay a solid foundation for big and fast data analysis, enabling a new integrated parallel processing paradigm, algorithms for critical order-related analytics, and a principled optimizer with strong performance guarantees. It will also broadly enable accelerated information discovery in emerging domains such as genomics, as well as economic benefits of early, well-informed decisions and reduced user payments.
Max ERC Funding
2 472 752 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym BinD
Project Mitotic Bookmarking, Stem Cells and early Development
Researcher (PI) Pablo Navarro Gil
Host Institution (HI) INSTITUT PASTEUR
Country France
Call Details Consolidator Grant (CoG), LS3, ERC-2017-COG
Summary The goal of this proposal is to deliver a new theoretical framework to understand how transcription factors (TFs) sustain cell identity during developmental processes. Recognised as key drivers of cell fate acquisition, TFs are currently not considered to directly contribute to the mitotic inheritance of chromatin states. Instead, these are passively propagated through cell division by a variety of epigenetic marks. Recent discoveries, including by our lab, challenge this view: developmental TFs may impact the propagation of regulatory information from mother to daughter cells through a process known as mitotic bookmarking. This hypothesis, largely overlooked by mainstream epigenetic research during the last two decades, will be investigated in embryo-derived stem cells and during early mouse development. Indeed, these immature cell identities are largely independent from canonical epigenetic repression; hence, current models cannot account for their properties. We will comprehensively identify mitotic bookmarking factors in stem cells and early embryos, establish their function in stem cell self-renewal, cell fate acquisition and dissect how they contribute to chromatin regulation in mitosis. This will allow us to study the relationships between bookmarking factors and other mechanisms of epigenetic inheritance. To achieve this, unique techniques to modulate protein activity and histone modifications specifically in mitotic cells will be established. Thus, a mechanistic understanding of how mitosis influences gene regulation and of how mitotic bookmarking contributes to the propagation of immature cell identities will be delivered. Based on robust preliminary data, we anticipate the discovery of new functions for TFs in several genetic and epigenetic processes. This knowledge should have a wide impact on chromatin biology and cell fate studies as well as in other fields studying processes dominated by TFs and cell proliferation.
Summary
The goal of this proposal is to deliver a new theoretical framework to understand how transcription factors (TFs) sustain cell identity during developmental processes. Recognised as key drivers of cell fate acquisition, TFs are currently not considered to directly contribute to the mitotic inheritance of chromatin states. Instead, these are passively propagated through cell division by a variety of epigenetic marks. Recent discoveries, including by our lab, challenge this view: developmental TFs may impact the propagation of regulatory information from mother to daughter cells through a process known as mitotic bookmarking. This hypothesis, largely overlooked by mainstream epigenetic research during the last two decades, will be investigated in embryo-derived stem cells and during early mouse development. Indeed, these immature cell identities are largely independent from canonical epigenetic repression; hence, current models cannot account for their properties. We will comprehensively identify mitotic bookmarking factors in stem cells and early embryos, establish their function in stem cell self-renewal, cell fate acquisition and dissect how they contribute to chromatin regulation in mitosis. This will allow us to study the relationships between bookmarking factors and other mechanisms of epigenetic inheritance. To achieve this, unique techniques to modulate protein activity and histone modifications specifically in mitotic cells will be established. Thus, a mechanistic understanding of how mitosis influences gene regulation and of how mitotic bookmarking contributes to the propagation of immature cell identities will be delivered. Based on robust preliminary data, we anticipate the discovery of new functions for TFs in several genetic and epigenetic processes. This knowledge should have a wide impact on chromatin biology and cell fate studies as well as in other fields studying processes dominated by TFs and cell proliferation.
Max ERC Funding
1 900 844 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym bioSPINspired
Project Bio-inspired Spin-Torque Computing Architectures
Researcher (PI) Julie Grollier
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Consolidator Grant (CoG), PE3, ERC-2015-CoG
Summary In the bioSPINspired project, I propose to use my experience and skills in spintronics, non-linear dynamics and neuromorphic nanodevices to realize bio-inspired spin torque computing architectures. I will develop a bottom-up approach to build spintronic data processing systems that perform low power ‘cognitive’ tasks on-chip and could ultimately complement our traditional microprocessors. I will start by showing that spin torque nanodevices, which are multi-functional and tunable nonlinear dynamical nano-components, are capable of emulating both neurons and synapses. Then I will assemble these spin-torque nano-synapses and nano-neurons into modules that implement brain-inspired algorithms in hardware. The brain displays many features typical of non-linear dynamical networks, such as synchronization or chaotic behaviour. These observations have inspired a whole class of models that harness the power of complex non-linear dynamical networks for computing. Following such schemes, I will interconnect the spin torque nanodevices by electrical and magnetic interactions so that they can couple to each other, synchronize and display complex dynamics. Then I will demonstrate that when perturbed by external inputs, these spin torque networks can perform recognition tasks by converging to an attractor state, or use the separation properties at the edge of chaos to classify data. In the process, I will revisit these brain-inspired abstract models to adapt them to the constraints of hardware implementations. Finally I will investigate how the spin torque modules can be efficiently connected together with CMOS buffers to perform higher level computing tasks. The table-top prototypes, hardware-adapted computing models and large-scale simulations developed in bioSPINspired will lay the foundations of spin torque bio-inspired computing and open the path to the fabrication of fully integrated, ultra-dense and efficient CMOS/spin-torque nanodevice chips.
Summary
In the bioSPINspired project, I propose to use my experience and skills in spintronics, non-linear dynamics and neuromorphic nanodevices to realize bio-inspired spin torque computing architectures. I will develop a bottom-up approach to build spintronic data processing systems that perform low power ‘cognitive’ tasks on-chip and could ultimately complement our traditional microprocessors. I will start by showing that spin torque nanodevices, which are multi-functional and tunable nonlinear dynamical nano-components, are capable of emulating both neurons and synapses. Then I will assemble these spin-torque nano-synapses and nano-neurons into modules that implement brain-inspired algorithms in hardware. The brain displays many features typical of non-linear dynamical networks, such as synchronization or chaotic behaviour. These observations have inspired a whole class of models that harness the power of complex non-linear dynamical networks for computing. Following such schemes, I will interconnect the spin torque nanodevices by electrical and magnetic interactions so that they can couple to each other, synchronize and display complex dynamics. Then I will demonstrate that when perturbed by external inputs, these spin torque networks can perform recognition tasks by converging to an attractor state, or use the separation properties at the edge of chaos to classify data. In the process, I will revisit these brain-inspired abstract models to adapt them to the constraints of hardware implementations. Finally I will investigate how the spin torque modules can be efficiently connected together with CMOS buffers to perform higher level computing tasks. The table-top prototypes, hardware-adapted computing models and large-scale simulations developed in bioSPINspired will lay the foundations of spin torque bio-inspired computing and open the path to the fabrication of fully integrated, ultra-dense and efficient CMOS/spin-torque nanodevice chips.
Max ERC Funding
1 907 767 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym BLACK
Project The formation and evolution of massive black holes
Researcher (PI) Marta Volonteri
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Consolidator Grant (CoG), PE9, ERC-2013-CoG
Summary "Massive black holes (MBHs) weighing million solar masses and above inhabit the centers of today's galaxies, weighing about a thousandth of the host bulge mass. MBHs also powered quasars known to exist just a few hundred million years after the Big Bang. Owing to observational breakthroughs and remarkable advancements in theoretical models, we do now that MBHs are out there and evolved with their hosts, but we do not know how they got there nor how, and when, the connection between MBHs and hosts was established.
To have a full view of MBH formation and growth we have to look at the global process where galaxies form, as determined by the large-scale structure, on Mpc scales. On the other hand, the region where MBHs dominate the dynamics of gas and stars, and accretion occurs, is merely pc-scale. To study the formation of MBHs and their fuelling we must bridge from Mpc to pc scale in order to follow how galaxies influence MBHs and how in turn MBHs influence galaxies.
BLACK aims to connect the cosmic context to the nuclear region where MBHs reside, and to study MBH formation, feeding and feedback on their hosts through a multi-scale approach following the thread of MBHs from cosmological, to galactic, to nuclear scales. Analytical work guides and tests numerical simulations, allowing us to probe a wide dynamical range.
Our theoretical work will be crucial for planning and interpreting current and future observations. Today and in the near future facilities at wavelengths spanning from radio to X-ray will widen and deepen our view of the Universe, making this an ideal time for this line of research."
Summary
"Massive black holes (MBHs) weighing million solar masses and above inhabit the centers of today's galaxies, weighing about a thousandth of the host bulge mass. MBHs also powered quasars known to exist just a few hundred million years after the Big Bang. Owing to observational breakthroughs and remarkable advancements in theoretical models, we do now that MBHs are out there and evolved with their hosts, but we do not know how they got there nor how, and when, the connection between MBHs and hosts was established.
To have a full view of MBH formation and growth we have to look at the global process where galaxies form, as determined by the large-scale structure, on Mpc scales. On the other hand, the region where MBHs dominate the dynamics of gas and stars, and accretion occurs, is merely pc-scale. To study the formation of MBHs and their fuelling we must bridge from Mpc to pc scale in order to follow how galaxies influence MBHs and how in turn MBHs influence galaxies.
BLACK aims to connect the cosmic context to the nuclear region where MBHs reside, and to study MBH formation, feeding and feedback on their hosts through a multi-scale approach following the thread of MBHs from cosmological, to galactic, to nuclear scales. Analytical work guides and tests numerical simulations, allowing us to probe a wide dynamical range.
Our theoretical work will be crucial for planning and interpreting current and future observations. Today and in the near future facilities at wavelengths spanning from radio to X-ray will widen and deepen our view of the Universe, making this an ideal time for this line of research."
Max ERC Funding
1 668 385 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym BRAINandMINDFULNESS
Project Impact of Mental Training of Attention and Emotion Regulation on Brain and Behavior: Implications for Neuroplasticity, Well-Being and Mindfulness Psychotherapy Research
Researcher (PI) Antoine Lutz
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Country France
Call Details Consolidator Grant (CoG), SH4, ERC-2013-CoG
Summary Mindfulness-based therapy has become an increasingly popular treatment to reduce stress, increase well-being and prevent relapse in depression. A key component of these therapies includes mindfulness practice that intends to train attention to detect and regulate afflictive cognitive and emotional patterns. Beyond its therapeutic application, the empirical study of mindfulness practice also represents a promising tool to understand practices that intentionally cultivate present-centeredness and openness to experience. Despite its clinical efficacy, little remains known about its means of action. Antithetic to this mode of experiential self-focus are states akin to depression, that are conducive of biased attention toward negativity, biased thoughts and rumination, and dysfunctional self schemas. The proposed research aims at implementing an innovative framework to scientifically investigate the experiential, cognitive, and neural processes underlining mindfulness practice building on the current neurocognitive understanding of the functional and anatomical architecture of cognitive control, and depression. To identify these mechanisms, this project aims to use paradigms from cognitive, and affective neuroscience (MEG, intracortical EEG, fMRI) to measure the training and plasticity of emotion regulation and cognitive control, and their effect on automatic, self-related affective processes. Using a cross-sectional design, this project aims to compare participants with trait differences in experiential self-focus mode. Using a longitudinal design, this project aims to explore mindfulness-practice training’s effect using a standard mindfulness-based intervention and an active control intervention. The PI has pioneered the neuroscientific investigation of mindfulness in the US and aspires to assemble a research team in France and a network of collaborators in Europe to pursue this research, which could lead to important outcomes for neuroscience, and mental health.
Summary
Mindfulness-based therapy has become an increasingly popular treatment to reduce stress, increase well-being and prevent relapse in depression. A key component of these therapies includes mindfulness practice that intends to train attention to detect and regulate afflictive cognitive and emotional patterns. Beyond its therapeutic application, the empirical study of mindfulness practice also represents a promising tool to understand practices that intentionally cultivate present-centeredness and openness to experience. Despite its clinical efficacy, little remains known about its means of action. Antithetic to this mode of experiential self-focus are states akin to depression, that are conducive of biased attention toward negativity, biased thoughts and rumination, and dysfunctional self schemas. The proposed research aims at implementing an innovative framework to scientifically investigate the experiential, cognitive, and neural processes underlining mindfulness practice building on the current neurocognitive understanding of the functional and anatomical architecture of cognitive control, and depression. To identify these mechanisms, this project aims to use paradigms from cognitive, and affective neuroscience (MEG, intracortical EEG, fMRI) to measure the training and plasticity of emotion regulation and cognitive control, and their effect on automatic, self-related affective processes. Using a cross-sectional design, this project aims to compare participants with trait differences in experiential self-focus mode. Using a longitudinal design, this project aims to explore mindfulness-practice training’s effect using a standard mindfulness-based intervention and an active control intervention. The PI has pioneered the neuroscientific investigation of mindfulness in the US and aspires to assemble a research team in France and a network of collaborators in Europe to pursue this research, which could lead to important outcomes for neuroscience, and mental health.
Max ERC Funding
1 868 520 €
Duration
Start date: 2014-11-01, End date: 2020-10-31
Project acronym CARINE
Project Coherent diffrAction foR a look Inside Nanostructures towards atomic rEsolution: catalysis and interface
Researcher (PI) Marie-Ingrid RICHARD
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Country France
Call Details Consolidator Grant (CoG), PE3, ERC-2018-COG
Summary Heterogeneous catalysis of nanoparticles has recently emerged as highly promising way to speed up catalytic processes due to their far higher surface area compared to bulk materials. But they face significant challenges in achieving high catalytic activity and sufficient durability. A key problem has been that all existing approaches to the characterization of atomic scale phenomena in these materials either lack structural specificity or can be employed under highly unrealistic catalytic environments. As an example, operando x-ray catalysis has often been carried out under idealized conditions and averaging information from macroscopic facets. This approach suffers from the lack of transferability to nanocrystalline systems. To tackle this problem, I am developing new state-of-the-art in situ techniques based on coherent x-ray scattering and complementary chemical characterization, with which I will optimize catalyst and reactor operations simultaneously. This is the ambition of the CARINE project to study in situ and operando the structural evolution of catalytic nanoparticles in realistic conditions during reaction by using the unique capabilities of coherent diffraction Bragg imaging (CDI). My proposed work builds on my recent exciting proof-of-concept experiments using Pt nanocrystals that demonstrate the sensitivity and spatial resolution of CDI under liquid conditions. As dedicated instruments for CDI have just reached user operation, it is only now that this new imaging technique can be applied during reaction and can probe structural changes of individual nanocrystals under conditions where up to now, no other techniques could probe the relevant parameters. My project will shed light into most relevant unsolved issues (durability, activity…) that limit the efficiency of today’s industrial processes and will open new horizons with outstanding impact in catalytic research.
Summary
Heterogeneous catalysis of nanoparticles has recently emerged as highly promising way to speed up catalytic processes due to their far higher surface area compared to bulk materials. But they face significant challenges in achieving high catalytic activity and sufficient durability. A key problem has been that all existing approaches to the characterization of atomic scale phenomena in these materials either lack structural specificity or can be employed under highly unrealistic catalytic environments. As an example, operando x-ray catalysis has often been carried out under idealized conditions and averaging information from macroscopic facets. This approach suffers from the lack of transferability to nanocrystalline systems. To tackle this problem, I am developing new state-of-the-art in situ techniques based on coherent x-ray scattering and complementary chemical characterization, with which I will optimize catalyst and reactor operations simultaneously. This is the ambition of the CARINE project to study in situ and operando the structural evolution of catalytic nanoparticles in realistic conditions during reaction by using the unique capabilities of coherent diffraction Bragg imaging (CDI). My proposed work builds on my recent exciting proof-of-concept experiments using Pt nanocrystals that demonstrate the sensitivity and spatial resolution of CDI under liquid conditions. As dedicated instruments for CDI have just reached user operation, it is only now that this new imaging technique can be applied during reaction and can probe structural changes of individual nanocrystals under conditions where up to now, no other techniques could probe the relevant parameters. My project will shed light into most relevant unsolved issues (durability, activity…) that limit the efficiency of today’s industrial processes and will open new horizons with outstanding impact in catalytic research.
Max ERC Funding
1 875 000 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
Project acronym Chap4Resp
Project Catching in action a novel bacterial chaperone for respiratory complexes
Researcher (PI) Irina Gutsche
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Consolidator Grant (CoG), LS1, ERC-2014-CoG
Summary Cellular respiration provides energy to power essential processes of life. Respiratory complexes are macromolecular batteries coupling electron flow through a wire of metal clusters and cofactors with proton transfer across the inner membrane of mitochondria and bacteria. Waste products of these cellular factories are reactive oxygen species causing ageing and diseases. Assembly and maturation mechanisms of respiratory complexes remain enigmatic because of their membrane location, multisubunit composition and cofactor insertion. E. coli Complex I, one of the largest membrane proteins, composed of 14 conserved subunits with 9 Fe/S clusters and a flavin, is a minimal model for its 45-subunit human homologue. When proton pumping by respiratory complexes is affected, bacteria become resistant to antibiotics requiring proton gradient for uptake. Based on the latest genetic data, we realize that the huge E. coli macromolecular cage, the structure of which we recently solved by cryo-electron microscopy (cryoEM), in conjunction with a novel protein cofactor, is a specific chaperone for Fe/S cluster biogenesis and assembly of respiratory complexes. This integrated multidisciplinary project combines cryoEM and other structural, biophysical and spectroscopic techniques, to uncover the functional mechanism of this emerging chaperone. The structural plasticity of the chaperone fuelled by ATP hydrolysis, and its interaction with Fe/S cluster biogenesis systems and the main respiratory complexes as a function of stresses, will be scrutinized to gain quasiatomic insights into the way the chaperone operates on its substrates. A novel technology for synergetic in situ investigation of protein complexes in the bacterial cytoplasm by optical imaging, state-of-the-art cryogenic correlative light and electron microscopy, and subtomogram analysis, will be developed and used to obtain snapshots of the chaperone-substrate interactions in the cellular context.
Summary
Cellular respiration provides energy to power essential processes of life. Respiratory complexes are macromolecular batteries coupling electron flow through a wire of metal clusters and cofactors with proton transfer across the inner membrane of mitochondria and bacteria. Waste products of these cellular factories are reactive oxygen species causing ageing and diseases. Assembly and maturation mechanisms of respiratory complexes remain enigmatic because of their membrane location, multisubunit composition and cofactor insertion. E. coli Complex I, one of the largest membrane proteins, composed of 14 conserved subunits with 9 Fe/S clusters and a flavin, is a minimal model for its 45-subunit human homologue. When proton pumping by respiratory complexes is affected, bacteria become resistant to antibiotics requiring proton gradient for uptake. Based on the latest genetic data, we realize that the huge E. coli macromolecular cage, the structure of which we recently solved by cryo-electron microscopy (cryoEM), in conjunction with a novel protein cofactor, is a specific chaperone for Fe/S cluster biogenesis and assembly of respiratory complexes. This integrated multidisciplinary project combines cryoEM and other structural, biophysical and spectroscopic techniques, to uncover the functional mechanism of this emerging chaperone. The structural plasticity of the chaperone fuelled by ATP hydrolysis, and its interaction with Fe/S cluster biogenesis systems and the main respiratory complexes as a function of stresses, will be scrutinized to gain quasiatomic insights into the way the chaperone operates on its substrates. A novel technology for synergetic in situ investigation of protein complexes in the bacterial cytoplasm by optical imaging, state-of-the-art cryogenic correlative light and electron microscopy, and subtomogram analysis, will be developed and used to obtain snapshots of the chaperone-substrate interactions in the cellular context.
Max ERC Funding
1 999 956 €
Duration
Start date: 2015-10-01, End date: 2022-03-31
Project acronym ChromoSOMe
Project Canonical and Non-canonical modes of Chromosome Segregation in Oocyte Meiosis
Researcher (PI) Julien Dumont
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Consolidator Grant (CoG), LS3, ERC-2018-COG
Summary Cell division is crucial for the development of complex organisms, for the homeostasis of tissues, and for the reproductive capacity of individuals. While most somatic cells are diploid and proliferate through mitosis, multiplication of sexually reproducing species relies on haploid gametes that are generated through a specialized cell division process called meiosis. To achieve this reduction in ploidy, two rounds of chromosome segregation follow a single phase of genome replication. Inaccuracy in this process leads to gametes that carry an incorrect number of chromosomes and to aneuploid embryos after fertilization. In their vast majority, these are non-viable and lead to spontaneous abortion: defective meiotic division is therefore a major obstacle in achieving reproduction. However, the key principles that drive this process are still poorly understood, one main reason being the diversity of the molecular scenarios that have been adopted across evolution to regulate oocyte chromosome segregation.
To dissect the key components of oocyte meiotic chromosome segregation, we propose to carry out a multi-disciplinary approach, combining several nematode species with the use of high-resolution live and electron microscopy, cutting edge genomic and proteomic technologies, and biochemistry coupled to in silico modeling. In Work Package 1 (WP1), we will analyze the molecular mechanisms controlling the self-assembly of the chromosome segregation machinery -the meiotic spindle- in the oocyte. WP2 will focus on defining how chromosome segregation is achieved in oocytes with non-canonical kinetochore geometry. WP3 aims at analyzing meiotic divisions in parthenogenetic nematodes with specific meiotic constraints, such as centrosomal oogenesis and unichromosomal genomes. By considering the wealth of mechanisms that can drive chromosome segregation in oocytes, this project will provide decisive steps towards understanding the essential and universal features of female meiosis.
Summary
Cell division is crucial for the development of complex organisms, for the homeostasis of tissues, and for the reproductive capacity of individuals. While most somatic cells are diploid and proliferate through mitosis, multiplication of sexually reproducing species relies on haploid gametes that are generated through a specialized cell division process called meiosis. To achieve this reduction in ploidy, two rounds of chromosome segregation follow a single phase of genome replication. Inaccuracy in this process leads to gametes that carry an incorrect number of chromosomes and to aneuploid embryos after fertilization. In their vast majority, these are non-viable and lead to spontaneous abortion: defective meiotic division is therefore a major obstacle in achieving reproduction. However, the key principles that drive this process are still poorly understood, one main reason being the diversity of the molecular scenarios that have been adopted across evolution to regulate oocyte chromosome segregation.
To dissect the key components of oocyte meiotic chromosome segregation, we propose to carry out a multi-disciplinary approach, combining several nematode species with the use of high-resolution live and electron microscopy, cutting edge genomic and proteomic technologies, and biochemistry coupled to in silico modeling. In Work Package 1 (WP1), we will analyze the molecular mechanisms controlling the self-assembly of the chromosome segregation machinery -the meiotic spindle- in the oocyte. WP2 will focus on defining how chromosome segregation is achieved in oocytes with non-canonical kinetochore geometry. WP3 aims at analyzing meiotic divisions in parthenogenetic nematodes with specific meiotic constraints, such as centrosomal oogenesis and unichromosomal genomes. By considering the wealth of mechanisms that can drive chromosome segregation in oocytes, this project will provide decisive steps towards understanding the essential and universal features of female meiosis.
Max ERC Funding
1 561 563 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
