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500 Projects, page 1 of 50

  • 2017-2021
  • European Commission
  • 2016
  • 2022

10
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  • Open Access mandate for Publications
    Funder: EC Project Code: 714693
    Overall Budget: 1,295,060 EURFunder Contribution: 1,295,060 EUR
    Partners: TSE

    In the last several decades, it has been extensively studied how strategic behavior of economic agents could affect the outcomes of various institutions. Game theory and mechanism design theory play key roles in understanding economic agents' possible behavior in those institutions, its welfare consequences, and how we should design economic institutions to achieve desired social objectives even if the agents behave strategically for their own interests. However, existing studies mostly focus on somewhat narrow classes of economic environments by imposing restrictive assumptions. The proposed projects aim at providing novel theoretical frameworks which enable us to study agents' behavior and desirable institutions under much less assumptions. I believe that the projects have significant relevance in policy recommendation in practice and empirical studies, even though the proposed projects are primarily theoretical. In mechanism design, most papers in the literature focus on environments with independently distributed private information. We propose two novel (robustness-based) approaches to analyze mechanism design in correlated environments, motivated by their practical and empirical relevance. The robustness brought by my approach can be useful to mitigate certain types of misspecifications in mechanism design in practice. Moreover, the desirable robust mechanisms I obtain appear to be more sensible, and hence, can be useful for empirical studies of auction and other mechanism design problems. In game theory, it is often assumed that the game to be played is common knowledge, or even with uncertainty, uncertain variables are assumed to follow a common-knowledge prior .However, in many situations in reality, those do not seem to be satisfied. Our goal is to provide a novel theoretical framework to predict players' behavior in such incompletely specified games, and to identify conditions for (monotone) comparative statics. Both could be useful in empirical studies.

  • Open Access mandate for Publications
    Funder: EC Project Code: 679001
    Overall Budget: 1,445,590 EURFunder Contribution: 1,445,590 EUR
    Partners: UdG

    Billions of years of evolution have made enzymes superb catalysts capable of accelerating reactions by several orders of magnitude. The underlying physical principles of their extraordinary catalytic power still remains highly debated, which makes the alteration of natural enzyme activities towards synthetically useful targets a tremendous challenge for modern chemical biology. The routine design of enzymes will, however, have large socio-economic benefits, as because of the enzymatic advantages the production costs of many drugs will be reduced and will allow industries to use environmentally friendly alternatives. The goal of this project is to make the routine design of proficient enzymes possible. Current computational and experimental approaches are able to confer natural enzymes new functionalities but are economically unviable and the catalytic efficiencies lag far behind their natural counterparts. The groundbreaking nature of NetMoDEzyme relies on the application of network models to reduce the complexity of the enzyme design paradigm and completely reformulate previous computational design approaches. The new protocol proposed accurately characterizes the enzyme conformational dynamics and customizes the included mutations by exploiting the correlated movement of the enzyme active site residues with distal regions. The guidelines for mutation are withdrawn from the costly directed evolution experimental technique, and the most proficient enzymes are easily identified via chemoinformatic models. The new strategy will be applied to develop proficient enzymes for the synthesis of enantiomerically pure β-blocker drugs for treating cardiovascular problems at a reduced cost. The experimental assays of our computational predictions will finally elucidate the potential of this genuinely new approach for mimicking Nature’s rules of evolution.

  • Open Access mandate for Publications
    Funder: EC Project Code: 682899
    Overall Budget: 1,868,990 EURFunder Contribution: 1,868,990 EUR
    Partners: WWU

    Human Papillomavirus Type 16 (HPV16), the paradigm cancer-causing HPV type, is a small, nonenveloped, DNA virus characterized by its complex life cycle coupled to differentiation of squamous epithelia. Due to this complexity, how HPV16 infects cells is an understudied field of research. Our previous work to define the cellular pathways that are hijacked for initial infection revealed uptake by a novel endocytosis mechanism, and the requirement for mitosis for nuclear delivery. Our findings indicated that nuclear envelope breakdown was required to access the nuclear space, and that the virus associated with mitotic chromatin during metaphase. This prolonged mitosis, a process beneficiary for infection. The viral L2 protein as part of incoming viruses mimics this on its own. The aim of this proposal is to reveal how HPV16 differentially modulates or takes advantage of the mitotic machinery for nuclear import in cells, tissues or during aging, and whether malignant cellular consequences arise. On the viral side, we will define the minimal properties of L2 to mediate association with cell chromatin and mitosis prolongation. On the cellular side, we will identify the protein(s) that mediate recruitment, and how it occurs in a detailed temporal/spatial manner. To elucidate the mechanism of mitotic prolongation and consequences thereof, we will identify which regulatory complex of mitosis is targeted, how it is induced, and whether it causes DNA damage or segregation errors. Finally, we will ascertain the influence of tissue differentiation and aging on this process. Using systems biology, proteomics, virology, cell biology, biochemistry, and a wide range of microscopy approaches we will unravel the complex interactions between HPV and the host cell mitosis machinery. In turn, as viruses often serve as valuable tools to study cell function, this work is likely to uncover new insights into how cells spatially and temporally regulate mitosis in differentiation and aging.

  • Open Access mandate for Publications
    Funder: EC Project Code: 646671
    Overall Budget: 1,999,020 EURFunder Contribution: 1,999,020 EUR
    Partners: VLAAMS INSTITUUT BIOTECHNOLOGIE FLANDERS INSTITUTE FOR BIOTECHNOLOGY

    Neurodegeneration is characterized by misfolded proteins and dysfunctional synapses. Synapses are often located very far away from their cell bodies and they must therefore largely independently cope with the unfolded, dysfunctional proteins that form as a result of synaptic activity and stress. My hypothesis is that synaptic terminals have adopted specific mechanisms to maintain robustness over their long lives and that these may become disrupted in neurodegenerative diseases. Recent evidence indicates an intriguing relationship between several Parkinson disease genes, synaptic vesicle trafficking and autophagy, providing an excellent entry point to study key molecular mechanisms and interactions in synaptic membrane trafficking and synaptic autophagy. We will use novel genome editing methodologies enabling fast in vivo structure-function studies in fruit flies and we will use differentiated human neurons to assess the conservation of mechanisms across evolution. In a complementary approach I also propose to capitalize on innovative in vitro liposome-based proteome-wide screening methods as well as in vivo genetic screens in fruit flies to find novel membrane-associated machines that mediate synaptic autophagy with the ultimate aim to reveal how these mechanisms regulate the maintenance of synaptic health. Our work not only has the capacity to uncover novel aspects in the regulation of presynaptic autophagy and function, but it will also reveal mechanisms of synaptic dysfunction in models of neuronal demise and open new research lines on mechanisms of synaptic plasticity.

  • Open Access mandate for Publications
    Funder: EC Project Code: 679175
    Overall Budget: 1,970,000 EURFunder Contribution: 1,970,000 EUR
    Partners: UZH

    Understanding how the mammalian brain network acquires its ability during development to process information and interact with the environment is one of the fundamental challenges in modern biology. The brain originates from a sheet of neural progenitors during embryogenesis but rapidly develops into distinct functional areas such as primary sensory and the highly associative cortices. Although all cortical areas consist of the same main neuronal elements, excitatory and inhibitory cells, their functions are markedly distinct. Unlike others, primary sensory cortical regions receive direct inputs from the environment through the respective thalamic nuclei starting at an early stage in development and are therefore likely to be shaped by incoming activity from sensory modalities. Despite the plethora of data on the arealization of the cortex by early signaling centers and the critical period plasticity mechanisms which take place after the basic elements of the circuit have been laid out, very little is known about the important period in between and how individual elements bind together to construct a functional circuit. This proposal is aimed at bridging this gap in knowledge, by addressing the long-standing question of how genes and activity interact during development to establish the correct wiring of excitatory and inhibitory cells in cortical sensory areas. As the primary role of inhibitory cells is to shape the flow of information transfer in the brain, they are well positioned to contribute significantly to the distinct modes of information processing performed in different cortical areas. Considering that dysfunction of cortical inhibitory circuits has been proposed as a major contributor to the etiology of neuropsychiatric-neurodevelopmental disorders, it is my hope that this approach will not only provide insights into the making of the healthy brain, but also into clinically relevant pathologies.

  • Open Access mandate for Publications
    Funder: EC Project Code: 692775
    Overall Budget: 2,497,980 EURFunder Contribution: 2,497,980 EUR
    Partners: Weizmann Institute of Science

    The discovery of novel sustainable catalytic reactions is a major current goal. Based on recent discoveries in our group, we plan to develop unprecedented sustainable catalytic reactions with special emphasis on reactions catalyzed by complexes of earth-abundant metals. We have recently discovered an intriguing reaction, namely the oxidation of organic compounds using water, with no added oxidant, evolving H2. This simple, selective reaction, offers now a novel, conceptually new, environmentally benign approach in the field of oxidation of organic compounds, which we will explore. We recently discovered a new mode of activation of multiple bonds by metal-ligand cooperation, including activation of CO2 and nitrile triple bonds, in which reversible C-C bond formation with the ligand is involved. Based on that, activation of nitriles has resulted in unprecedented C-C bond formation involving addition of simple aliphatic nitriles to various α,β-unsaturated carbonyl compounds. This mode of multiple bond activation may open a new approach to catalysis, “template catalysis”, which we plan to explore. In addition, the highly desirable, catalytic activation of the kinetically very stable, potent greenhouse gas N2O for the (so far elusive), efficient oxygen transfer to organic compounds, will be pursued. The use of CO2 in organic synthesis is an important timely topic. Based on its activation by metal ligand cooperation, new catalytic reactions of CO2 will be pursued, including unprecedented carbonylation of non-activated C-H bonds. Most reactions catalysed by metal complexes involve noble metals. Development of sustainable catalysis based on complexes of earth-abundant metals is of great interest. In all topics described above, catalysis by complexes of such metals will be emphasized. Moreover, based on recent results in our group, we plan to develop an unprecedented family of complexes of earth-abundant metals, and pursue novel sustainable catalysis, based on it.

  • Open Access mandate for Publications
    Funder: EC Project Code: 694122
    Overall Budget: 2,461,090 EURFunder Contribution: 2,461,090 EUR
    Partners: INRIA

    Light fields technology holds great promises in computational imaging. Light fields cameras capture light rays as they interact with physical objects in the scene. The recorded flow of rays (the light field) yields a rich description of the scene enabling advanced image creation capabilities from a single capture. This technology is expected to bring disruptive changes in computational imaging. However, the trajectory to a deployment of light fields remains cumbersome. Bottlenecks need to be alleviated before being able to fully exploit its potential. Barriers that CLIM addresses are the huge amount of high-dimensional (4D/5D) data produced by light fields, limitations of capturing devices, editing and image creation capabilities from compressed light fields. These barriers cannot be overcome by a simple application of methods which have made the success of digital imaging in past decades. The 4D/5D sampling of the geometric distribution of light rays striking the camera sensors imply radical changes in the signal processing chain compared to traditional imaging systems. The ambition of CLIM is to lay new algorithmic foundations for the 4D/5D light fields processing chain, going from representation, compression to rendering. Data processing becomes tougher as dimensionality increases, which is the case of light fields compared to 2D images. This leads to the first challenge of CLIM that is the development of methods for low dimensional embedding and sparse representations of 4D/5D light fields. The second challenge is to develop a coding/decoding architecture for light fields which will exploit their geometrical models while preserving the structures that are critical for advanced image creation capabilities. CLIM targets ground-breaking solutions which should open new horizons for a number of consumer and professional markets (photography, augmented reality, light field microscopy, medical imaging, particle image velocimetry).

  • Open Access mandate for Publications
    Funder: EC Project Code: 681630
    Overall Budget: 1,999,010 EURFunder Contribution: 1,999,010 EUR
    Partners: IRB

    Homologous recombination plays a crucial role to repair DNA strand breaks that may occur spontaneously upon replication fork collapse, during the course of radio- or chemotherapy or in a programmed manner during meiosis. Understanding the molecular mechanisms of re-combinational repair is thus very important not only from a basic research viewpoint, but it is also highly relevant for human health. Here, we will define the function of nucleases in homol-ogous recombination. First, we will study the initial steps in this pathway. We could show previously that the S. cerevisiae Sae2 protein promotes the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex near protein blocked DNA ends. This initiates nucleolytic resection of DNA breaks and activates homologous recombination. Our biochemical setup will be instrumental to define how is the activity of Sae2 regulated by phosphorylation on a mech-anistic level and how physiological protein blocks direct the Mre11 endonuclease. We will ex-tend the study to the human system, and attempt to apply the gained knowledge to improve the efficiency of genome editing by activating recombination in conjunction with the CRISPR-Cas9 nuclease system. Second, we will study how homologous recombination promotes gen-eration of genetic diversity during sexual reproduction. DNA strand breaks are introduced in-tentionally during the prophase of the first meiotic division. They are then processed by the recombination machinery into Holliday junction intermediates. These joint molecules are preferentially converted into crossovers in meiosis, resulting in exchange of genetic infor-mation between the maternal and paternal DNA molecules. This is dependent on the Mlh1-Mlh3 nuclease through a yet unknown mechanism. We will study how Mlh1-Mlh3 in complex with other proteins guarantee crossover outcome to promote diversity of the progeny.

  • Open Access mandate for Publications and Research data
    Funder: EC Project Code: 682903
    Overall Budget: 1,859,410 EURFunder Contribution: 1,859,410 EUR
    Partners: University of Bordeaux

    Despite the tremendous progress achieved over the past decade, the study of stellar formation is far from complete. We have not yet measured the minimum mass for star formation, nor the shape of the IMF down to the least massive free-floating planets, or know how universal this shape is. Although clusters are the building blocks of galaxies, little is known about their early dynamical evolution and dispersal into the field. The main culprit for this state of affairs is the high level of contamination and incompleteness in the sub-stellar regime, even for the best photometric and astrometric surveys. COSMIC-DANCE aims at overcoming these drawbacks and revealing the shape of the IMF with a precision and completeness surpassing current and foreseeable surveys of the next 15 years. We will: 1) Measure: using a groundbreaking, proven and so far unique method I designed, we will measure proper motions with an accuracy comparable to Gaia but 5 magnitudes deeper, reaching the planetary mass domain, and, critically, piercing through the dust obscured young clusters inaccessible to Gaia’s optical sensors. 2) Discover: feeding these proper motions and the multi-wavelength photometry to innovative hyper-dimensional data mining techniques, we will securely identify cluster members within the millions of sources of the COSMIC-DANCE database, complemented by Gaia at the bright end, to obtain the final census over the entire mass spectrum for 20 young nearby clusters, the end of a 60-year quest. 3) Understand: by providing conclusive empirical constraints over a broad parameter space unaccessible to current state-of-the-art surveys on the much debated respective contributions of evolutionary effects (dynamics, feedback and competitive accretion) and initial conditions (core properties) to the shape and bottom of the IMF, the most fundamental and informative product of star formation, with essential bearings on many areas of general astrophysics.

  • Open Access mandate for Publications
    Funder: EC Project Code: 695709
    Overall Budget: 2,495,560 EURFunder Contribution: 2,495,560 EUR
    Partners: UCL

    This proposal aims to address a simple question: what is the fundamental unit of computation in the brain? Answering this question is crucial not only for understanding how the brain works, but also if we are to build accurate models of brain function, which require abstraction based on identification of the essential elements for carrying out computations relevant to behaviour. In this proposal, we will build on recent work demonstrating that dendrites are highly electrically excitable to test the possibility that single dendritic branches may act as individual computational units during behaviour, challenging the classical view that the neuron is the fundamental unit of computation. We will address this question using a combination of electrophysiolgical, anatomical, imaging, molecular, and modeling approaches to probe dendritic integration in pyramidal cells and Purkinje cells in mouse cortex and cerebellum. We will first define the computational rules for integration of synaptic input in single and multiple dendrites by examining the somatic and dendritic responses to different spatiotemporal patterns of excitatory and inhibitory inputs in brain slices. Next, we will determine how these rules are engaged by patterns of sensory stimulation in vivo, by using various strategies to map the spatiotemporal patterns of synaptic inputs onto single dendrites. To understand how physiological patterns of activity in the circuit engage these dendritic computations, we will use anatomical approaches to map the wiring diagram of synaptic inputs to individual dendrites. Finally, we will perturb the dendritic computational rules by manipulating dendritic function using molecular and optogenetic tools, in order to provide causal links between specific dendritic computations and sensory processing relevant to behaviour. These experiments will provide us with deeper insights into how single neurons act as computing devices.

search
500 Projects, page 1 of 50
  • Open Access mandate for Publications
    Funder: EC Project Code: 714693
    Overall Budget: 1,295,060 EURFunder Contribution: 1,295,060 EUR
    Partners: TSE

    In the last several decades, it has been extensively studied how strategic behavior of economic agents could affect the outcomes of various institutions. Game theory and mechanism design theory play key roles in understanding economic agents' possible behavior in those institutions, its welfare consequences, and how we should design economic institutions to achieve desired social objectives even if the agents behave strategically for their own interests. However, existing studies mostly focus on somewhat narrow classes of economic environments by imposing restrictive assumptions. The proposed projects aim at providing novel theoretical frameworks which enable us to study agents' behavior and desirable institutions under much less assumptions. I believe that the projects have significant relevance in policy recommendation in practice and empirical studies, even though the proposed projects are primarily theoretical. In mechanism design, most papers in the literature focus on environments with independently distributed private information. We propose two novel (robustness-based) approaches to analyze mechanism design in correlated environments, motivated by their practical and empirical relevance. The robustness brought by my approach can be useful to mitigate certain types of misspecifications in mechanism design in practice. Moreover, the desirable robust mechanisms I obtain appear to be more sensible, and hence, can be useful for empirical studies of auction and other mechanism design problems. In game theory, it is often assumed that the game to be played is common knowledge, or even with uncertainty, uncertain variables are assumed to follow a common-knowledge prior .However, in many situations in reality, those do not seem to be satisfied. Our goal is to provide a novel theoretical framework to predict players' behavior in such incompletely specified games, and to identify conditions for (monotone) comparative statics. Both could be useful in empirical studies.

  • Open Access mandate for Publications
    Funder: EC Project Code: 679001
    Overall Budget: 1,445,590 EURFunder Contribution: 1,445,590 EUR
    Partners: UdG

    Billions of years of evolution have made enzymes superb catalysts capable of accelerating reactions by several orders of magnitude. The underlying physical principles of their extraordinary catalytic power still remains highly debated, which makes the alteration of natural enzyme activities towards synthetically useful targets a tremendous challenge for modern chemical biology. The routine design of enzymes will, however, have large socio-economic benefits, as because of the enzymatic advantages the production costs of many drugs will be reduced and will allow industries to use environmentally friendly alternatives. The goal of this project is to make the routine design of proficient enzymes possible. Current computational and experimental approaches are able to confer natural enzymes new functionalities but are economically unviable and the catalytic efficiencies lag far behind their natural counterparts. The groundbreaking nature of NetMoDEzyme relies on the application of network models to reduce the complexity of the enzyme design paradigm and completely reformulate previous computational design approaches. The new protocol proposed accurately characterizes the enzyme conformational dynamics and customizes the included mutations by exploiting the correlated movement of the enzyme active site residues with distal regions. The guidelines for mutation are withdrawn from the costly directed evolution experimental technique, and the most proficient enzymes are easily identified via chemoinformatic models. The new strategy will be applied to develop proficient enzymes for the synthesis of enantiomerically pure β-blocker drugs for treating cardiovascular problems at a reduced cost. The experimental assays of our computational predictions will finally elucidate the potential of this genuinely new approach for mimicking Nature’s rules of evolution.

  • Open Access mandate for Publications
    Funder: EC Project Code: 682899
    Overall Budget: 1,868,990 EURFunder Contribution: 1,868,990 EUR
    Partners: WWU

    Human Papillomavirus Type 16 (HPV16), the paradigm cancer-causing HPV type, is a small, nonenveloped, DNA virus characterized by its complex life cycle coupled to differentiation of squamous epithelia. Due to this complexity, how HPV16 infects cells is an understudied field of research. Our previous work to define the cellular pathways that are hijacked for initial infection revealed uptake by a novel endocytosis mechanism, and the requirement for mitosis for nuclear delivery. Our findings indicated that nuclear envelope breakdown was required to access the nuclear space, and that the virus associated with mitotic chromatin during metaphase. This prolonged mitosis, a process beneficiary for infection. The viral L2 protein as part of incoming viruses mimics this on its own. The aim of this proposal is to reveal how HPV16 differentially modulates or takes advantage of the mitotic machinery for nuclear import in cells, tissues or during aging, and whether malignant cellular consequences arise. On the viral side, we will define the minimal properties of L2 to mediate association with cell chromatin and mitosis prolongation. On the cellular side, we will identify the protein(s) that mediate recruitment, and how it occurs in a detailed temporal/spatial manner. To elucidate the mechanism of mitotic prolongation and consequences thereof, we will identify which regulatory complex of mitosis is targeted, how it is induced, and whether it causes DNA damage or segregation errors. Finally, we will ascertain the influence of tissue differentiation and aging on this process. Using systems biology, proteomics, virology, cell biology, biochemistry, and a wide range of microscopy approaches we will unravel the complex interactions between HPV and the host cell mitosis machinery. In turn, as viruses often serve as valuable tools to study cell function, this work is likely to uncover new insights into how cells spatially and temporally regulate mitosis in differentiation and aging.

  • Open Access mandate for Publications
    Funder: EC Project Code: 646671
    Overall Budget: 1,999,020 EURFunder Contribution: 1,999,020 EUR
    Partners: VLAAMS INSTITUUT BIOTECHNOLOGIE FLANDERS INSTITUTE FOR BIOTECHNOLOGY

    Neurodegeneration is characterized by misfolded proteins and dysfunctional synapses. Synapses are often located very far away from their cell bodies and they must therefore largely independently cope with the unfolded, dysfunctional proteins that form as a result of synaptic activity and stress. My hypothesis is that synaptic terminals have adopted specific mechanisms to maintain robustness over their long lives and that these may become disrupted in neurodegenerative diseases. Recent evidence indicates an intriguing relationship between several Parkinson disease genes, synaptic vesicle trafficking and autophagy, providing an excellent entry point to study key molecular mechanisms and interactions in synaptic membrane trafficking and synaptic autophagy. We will use novel genome editing methodologies enabling fast in vivo structure-function studies in fruit flies and we will use differentiated human neurons to assess the conservation of mechanisms across evolution. In a complementary approach I also propose to capitalize on innovative in vitro liposome-based proteome-wide screening methods as well as in vivo genetic screens in fruit flies to find novel membrane-associated machines that mediate synaptic autophagy with the ultimate aim to reveal how these mechanisms regulate the maintenance of synaptic health. Our work not only has the capacity to uncover novel aspects in the regulation of presynaptic autophagy and function, but it will also reveal mechanisms of synaptic dysfunction in models of neuronal demise and open new research lines on mechanisms of synaptic plasticity.

  • Open Access mandate for Publications
    Funder: EC Project Code: 679175
    Overall Budget: 1,970,000 EURFunder Contribution: 1,970,000 EUR
    Partners: UZH

    Understanding how the mammalian brain network acquires its ability during development to process information and interact with the environment is one of the fundamental challenges in modern biology. The brain originates from a sheet of neural progenitors during embryogenesis but rapidly develops into distinct functional areas such as primary sensory and the highly associative cortices. Although all cortical areas consist of the same main neuronal elements, excitatory and inhibitory cells, their functions are markedly distinct. Unlike others, primary sensory cortical regions receive direct inputs from the environment through the respective thalamic nuclei starting at an early stage in development and are therefore likely to be shaped by incoming activity from sensory modalities. Despite the plethora of data on the arealization of the cortex by early signaling centers and the critical period plasticity mechanisms which take place after the basic elements of the circuit have been laid out, very little is known about the important period in between and how individual elements bind together to construct a functional circuit. This proposal is aimed at bridging this gap in knowledge, by addressing the long-standing question of how genes and activity interact during development to establish the correct wiring of excitatory and inhibitory cells in cortical sensory areas. As the primary role of inhibitory cells is to shape the flow of information transfer in the brain, they are well positioned to contribute significantly to the distinct modes of information processing performed in different cortical areas. Considering that dysfunction of cortical inhibitory circuits has been proposed as a major contributor to the etiology of neuropsychiatric-neurodevelopmental disorders, it is my hope that this approach will not only provide insights into the making of the healthy brain, but also into clinically relevant pathologies.

  • Open Access mandate for Publications
    Funder: EC Project Code: 692775
    Overall Budget: 2,497,980 EURFunder Contribution: 2,497,980 EUR
    Partners: Weizmann Institute of Science

    The discovery of novel sustainable catalytic reactions is a major current goal. Based on recent discoveries in our group, we plan to develop unprecedented sustainable catalytic reactions with special emphasis on reactions catalyzed by complexes of earth-abundant metals. We have recently discovered an intriguing reaction, namely the oxidation of organic compounds using water, with no added oxidant, evolving H2. This simple, selective reaction, offers now a novel, conceptually new, environmentally benign approach in the field of oxidation of organic compounds, which we will explore. We recently discovered a new mode of activation of multiple bonds by metal-ligand cooperation, including activation of CO2 and nitrile triple bonds, in which reversible C-C bond formation with the ligand is involved. Based on that, activation of nitriles has resulted in unprecedented C-C bond formation involving addition of simple aliphatic nitriles to various α,β-unsaturated carbonyl compounds. This mode of multiple bond activation may open a new approach to catalysis, “template catalysis”, which we plan to explore. In addition, the highly desirable, catalytic activation of the kinetically very stable, potent greenhouse gas N2O for the (so far elusive), efficient oxygen transfer to organic compounds, will be pursued. The use of CO2 in organic synthesis is an important timely topic. Based on its activation by metal ligand cooperation, new catalytic reactions of CO2 will be pursued, including unprecedented carbonylation of non-activated C-H bonds. Most reactions catalysed by metal complexes involve noble metals. Development of sustainable catalysis based on complexes of earth-abundant metals is of great interest. In all topics described above, catalysis by complexes of such metals will be emphasized. Moreover, based on recent results in our group, we plan to develop an unprecedented family of complexes of earth-abundant metals, and pursue novel sustainable catalysis, based on it.

  • Open Access mandate for Publications
    Funder: EC Project Code: 694122
    Overall Budget: 2,461,090 EURFunder Contribution: 2,461,090 EUR
    Partners: INRIA

    Light fields technology holds great promises in computational imaging. Light fields cameras capture light rays as they interact with physical objects in the scene. The recorded flow of rays (the light field) yields a rich description of the scene enabling advanced image creation capabilities from a single capture. This technology is expected to bring disruptive changes in computational imaging. However, the trajectory to a deployment of light fields remains cumbersome. Bottlenecks need to be alleviated before being able to fully exploit its potential. Barriers that CLIM addresses are the huge amount of high-dimensional (4D/5D) data produced by light fields, limitations of capturing devices, editing and image creation capabilities from compressed light fields. These barriers cannot be overcome by a simple application of methods which have made the success of digital imaging in past decades. The 4D/5D sampling of the geometric distribution of light rays striking the camera sensors imply radical changes in the signal processing chain compared to traditional imaging systems. The ambition of CLIM is to lay new algorithmic foundations for the 4D/5D light fields processing chain, going from representation, compression to rendering. Data processing becomes tougher as dimensionality increases, which is the case of light fields compared to 2D images. This leads to the first challenge of CLIM that is the development of methods for low dimensional embedding and sparse representations of 4D/5D light fields. The second challenge is to develop a coding/decoding architecture for light fields which will exploit their geometrical models while preserving the structures that are critical for advanced image creation capabilities. CLIM targets ground-breaking solutions which should open new horizons for a number of consumer and professional markets (photography, augmented reality, light field microscopy, medical imaging, particle image velocimetry).

  • Open Access mandate for Publications
    Funder: EC Project Code: 681630
    Overall Budget: 1,999,010 EURFunder Contribution: 1,999,010 EUR
    Partners: IRB

    Homologous recombination plays a crucial role to repair DNA strand breaks that may occur spontaneously upon replication fork collapse, during the course of radio- or chemotherapy or in a programmed manner during meiosis. Understanding the molecular mechanisms of re-combinational repair is thus very important not only from a basic research viewpoint, but it is also highly relevant for human health. Here, we will define the function of nucleases in homol-ogous recombination. First, we will study the initial steps in this pathway. We could show previously that the S. cerevisiae Sae2 protein promotes the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex near protein blocked DNA ends. This initiates nucleolytic resection of DNA breaks and activates homologous recombination. Our biochemical setup will be instrumental to define how is the activity of Sae2 regulated by phosphorylation on a mech-anistic level and how physiological protein blocks direct the Mre11 endonuclease. We will ex-tend the study to the human system, and attempt to apply the gained knowledge to improve the efficiency of genome editing by activating recombination in conjunction with the CRISPR-Cas9 nuclease system. Second, we will study how homologous recombination promotes gen-eration of genetic diversity during sexual reproduction. DNA strand breaks are introduced in-tentionally during the prophase of the first meiotic division. They are then processed by the recombination machinery into Holliday junction intermediates. These joint molecules are preferentially converted into crossovers in meiosis, resulting in exchange of genetic infor-mation between the maternal and paternal DNA molecules. This is dependent on the Mlh1-Mlh3 nuclease through a yet unknown mechanism. We will study how Mlh1-Mlh3 in complex with other proteins guarantee crossover outcome to promote diversity of the progeny.

  • Open Access mandate for Publications and Research data
    Funder: EC Project Code: 682903
    Overall Budget: 1,859,410 EURFunder Contribution: 1,859,410 EUR
    Partners: University of Bordeaux

    Despite the tremendous progress achieved over the past decade, the study of stellar formation is far from complete. We have not yet measured the minimum mass for star formation, nor the shape of the IMF down to the least massive free-floating planets, or know how universal this shape is. Although clusters are the building blocks of galaxies, little is known about their early dynamical evolution and dispersal into the field. The main culprit for this state of affairs is the high level of contamination and incompleteness in the sub-stellar regime, even for the best photometric and astrometric surveys. COSMIC-DANCE aims at overcoming these drawbacks and revealing the shape of the IMF with a precision and completeness surpassing current and foreseeable surveys of the next 15 years. We will: 1) Measure: using a groundbreaking, proven and so far unique method I designed, we will measure proper motions with an accuracy comparable to Gaia but 5 magnitudes deeper, reaching the planetary mass domain, and, critically, piercing through the dust obscured young clusters inaccessible to Gaia’s optical sensors. 2) Discover: feeding these proper motions and the multi-wavelength photometry to innovative hyper-dimensional data mining techniques, we will securely identify cluster members within the millions of sources of the COSMIC-DANCE database, complemented by Gaia at the bright end, to obtain the final census over the entire mass spectrum for 20 young nearby clusters, the end of a 60-year quest. 3) Understand: by providing conclusive empirical constraints over a broad parameter space unaccessible to current state-of-the-art surveys on the much debated respective contributions of evolutionary effects (dynamics, feedback and competitive accretion) and initial conditions (core properties) to the shape and bottom of the IMF, the most fundamental and informative product of star formation, with essential bearings on many areas of general astrophysics.

  • Open Access mandate for Publications
    Funder: EC Project Code: 695709
    Overall Budget: 2,495,560 EURFunder Contribution: 2,495,560 EUR
    Partners: UCL

    This proposal aims to address a simple question: what is the fundamental unit of computation in the brain? Answering this question is crucial not only for understanding how the brain works, but also if we are to build accurate models of brain function, which require abstraction based on identification of the essential elements for carrying out computations relevant to behaviour. In this proposal, we will build on recent work demonstrating that dendrites are highly electrically excitable to test the possibility that single dendritic branches may act as individual computational units during behaviour, challenging the classical view that the neuron is the fundamental unit of computation. We will address this question using a combination of electrophysiolgical, anatomical, imaging, molecular, and modeling approaches to probe dendritic integration in pyramidal cells and Purkinje cells in mouse cortex and cerebellum. We will first define the computational rules for integration of synaptic input in single and multiple dendrites by examining the somatic and dendritic responses to different spatiotemporal patterns of excitatory and inhibitory inputs in brain slices. Next, we will determine how these rules are engaged by patterns of sensory stimulation in vivo, by using various strategies to map the spatiotemporal patterns of synaptic inputs onto single dendrites. To understand how physiological patterns of activity in the circuit engage these dendritic computations, we will use anatomical approaches to map the wiring diagram of synaptic inputs to individual dendrites. Finally, we will perturb the dendritic computational rules by manipulating dendritic function using molecular and optogenetic tools, in order to provide causal links between specific dendritic computations and sensory processing relevant to behaviour. These experiments will provide us with deeper insights into how single neurons act as computing devices.

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