Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : STENIPATH (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2499600.0 €

Coherent tissue growth and repair require an interplay between stem cells and their local and systemic environment. The dynamics of this process remains poorly defined particularly at the intersection with disease. Cellular quiescence is adopted by many adult stem cells, conferring them several features including a smaller cell volume and reduced metabolic demand, suggesting that quiescence preserves stem cell properties making them less responsive to external cues. We examined the status of skeletal muscle stem (MuSC) and niche cells during an influenza virus infection (lung) and cancer cachexia (tumour) in mice. Unexpectedly, quiescent MuSCs remodelled their cellular, metabolic, and transcriptome properties extensively, and tissue regeneration was impaired, prompting us to define a novel cell state, GPath. Whether GPath represents a coordinated response of stem cells to pathology, or uncontrolled deregulation, is unclear.  MuSCs exhibit remarkable diversity in gene regulation and function in distinct anatomical locations (head/limb). We discovered that cranial MuSCs display higher resistance to the pathologies compared to those in limb. These observations have led us into a novel area of research, to the best of my knowledge largely unexplored in model organisms and humans: how stem and niche cells in one organ respond to pathologies present at a distal site. We will examine the response of muscle and blood stem and niche cells to distal pathologies by defining their cellular, metabolic, molecular, epigenetic, and functional properties, and their modes of cell division. We will employ diverse multiomics approaches and novel medium/high-throughput intravital and ex vivo imaging pipelines. This work should provide new knowledge and tools to address an important, but under-investigated area of research where stem cell biology and pathologies converge. The knowledge gained will be widely applicable to other stem cell systems and inform on human pathologies.

Mots-clés : quiescence,muscle stem cells,influenza virus,cancer cachexia,symmetric and asymmetric divisions,intravital imaging mouse,regeneration,stem cell heterogeneity,gastruloids,craniofacial development
Projet ERC : DormantAD (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Neuronal circuits must balance stability and plasticity. How this balance is compromised in brain disorders remains one of the most fundamental questions in neuroscience. Pioneering studies in the field established that homeostatic mechanisms stabilize the function of a system at a set-point level of activity. Recently, we have identified bona fide mitochondrial regulator of activity set points and provided support to our standing hypothesis that homeostatic failures destabilize network activity in Alzheimer's disease (AD). However, we have just scratched the surface of the mechanisms stabilizing activity set points in vivo. I propose a conceptual and experimental framework to identify the cellular-molecular and circuit-wide in vivo mechanisms underlying stability of hippocampal circuits across distinct brain states and stability-plasticity balance. Using a wide range of optical, electrophysiological, computational and molecular tools, we will explore homeostatic regulation of activity in hippocampal circuitry, a crucial substrate for memory formation, and its relation to AD. First, we will establish governing principles of homeostatic regulation in physiological context of sleep and learning. Next, we will explore the underlying molecular drivers of homeostatic regulation. Finally, we will test the causal relationship between dyshomeostasis of activity in hippocampal circuits, sleep disturbances and cognitive decline in AD models. To target these questions, we will utilize the basic concepts of control theory and an integrative approach which spans brain-state, neural circuit, synaptic and molecular levels. We believe that this understanding is an essential step to uncover the principle basis underlying the transition from a presymptomatic disease stage to clinically evident cognitive AD impairments. The proposed research will elucidate fundamental principles of neuronal function and reveal conceptually novel insights into how to maintain AD in a dormant state.

Mots-clés : homeostatic plasticity,synaptic transmission,synaptic plasticity,firing rate homeostasis,hippocampus,electrophysiology,calcium imaging,mitochondria,alzheimer s disease
Projet ERC : NFITSC (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1843125.0 €

Information-theoretic secure computation is a general-purpose technique for processing sensitive data without compromising its confidentiality or integrity even in the presence of a computationally-unbounded all-powerful adversary. This notion plays an important role in cryptography, both as a stand-alone object and as a tool for computational constructs. Despite its increasing importance, we have a very limited understanding of the *intrinsic complexity* of information-theoretic security, and some of the most central feasibility questions in this area have remained open for more than three decades.  In this proposal, we aim to decipher the power and limitations of this notion. We will focus on three main objectives. First, we aim to improve the complexity of general *secret sharing schemes* and exploit such improvements towards realizing highly-efficient general-purpose zero-knowledge proofs. The second objective is to explore the complexity of Secure Non-Interactive Reductions and Multiparty Randomized Encoding -- a powerful generalization of information-theoretic garbled circuits that was recently presented by the PI. The third objective is to expand our theoretical understanding of constant-round information-theoretic protocols, optimize their round complexity, and study their concrete and asymptotic computational complexity.  Being part of several recent exciting developments in these areas, we believe that it is now possible to make progress in some of these basic open problems. The suggested research will bridge across different regions of computer science such as coding theory, cryptography, and computational complexity. It is expected to impact central problems in cryptography, while enriching the general landscape of theoretical computer science.

Mots-clés : secure multiparty computation,secret sharing,information theoretic cryptography
Projet ERC : TRASUS (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Studies of Cultures and Arts
Entité participante : London School of Economics and Political Science — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : LSE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499037.0 €

TRASUS investigates how religious and political truths move across boundaries. The objectives are to identify the modalities of how truths travel, to propel incisive understandings of how truth-values are attached to collective ideas, and how the resulting truths configure and reconfigure social worlds. Such an in-depth study that theorizes the workings of truth is of paramount importance in an age of misinformation and fake news, in which the transmission of truth is a crucial weapon of power.  The project will examine the ‘trade of truths’ along three modalities of transmission (which can intersect and overlap): a missionary modality involving the projection of truth onto those ‘in need’; a diplomatic modality involving the tactful mediation and management of knowledge; and an extractive modality geared towards excavating hidden truths. These modalities will be tested in the South Caucasus, a region onto which expansionist projects have long projected their civilizing truths, and where sociopolitical fragmentation confounds the exchange of knowledge. By carrying out six case studies, the project will examine how these modalities are mobilized in missionary endeavors aimed at converting others, in the projection of nationalist truths onto ethnically cleansed areas, in efforts to mediate between opposing ethnic and religious groups, and in top-down practices of surveillance and bottom-up efforts of critique. Based on long-term, historically informed ethnographic field research, the project will analyze how old and new technologies are mobilized in knowledge encounters, follow relevant ‘truth merchants’, and trace the trajectories of specific truths claims. In doing so, TRASUS will reveal the shifting interlocking of epistemic objects, human engagements with them, and the situations in which they are entangled. This will offer comprehensive and dynamic understandings of how truth is produced; and it will produce new insight into the biases, gaps, and limita

Mots-clés : missionary activity everyday diplomacy surveillance conspiracy theorizing truth making
Projet ERC : Genome2Cells (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

The genome of an animal encodes a large set of regulatory programs that give rise to the thousands of cell types that make up its tissues and organs. Despite recent progress in single-cell omics, our knowledge about the regulatory programs that control the establishment and maintenance of cell type identity remains limited, and methods are lacking to infer regulatory programs directly from the genome sequence. In this project, which lies at the interface between the genome and single-cell atlases, we ask how the genome sequence “translates” into cell types. We start with Drosophila as model organism. Its compactness allows sampling of all its cell types and developmental trajectories from egg to adult, using whole-organism single-cell multi-omics, thus capturing the spectrum of “activation states” that emerge from the regulatory genome. Deep learning models will be trained on regulatory sequences to predict and explain gene regulatory networks (GRN) and GRN transitions between cell states, encoded by enhancers, promoters, transcription factors (TF), effector genes, and feedback loops. Based on a better mechanistic understanding, we will translate this framework to other animals, including octopus, birds, and mammals, and ask how regulatory programs evolve, with a focus on neuronal diversity in the brain. Using new algorithms for cross-species deep learning and combinatorial optimization, we will study how combinations of expressed TFs co-evolve with genomic enhancer logic. We are unique in our approach because we will develop and use new technological assays, deep learning, and massively parallel reporter assays, and combine these with perturbation experiments and synthetic biology to test our hypotheses. After iteratively improving our regulatory models, we ultimately aim to predict which regulatory programs, and thus which cell types, are encoded in an animal’s genome, and how changes in these programs underlie changes in cell types during evolution.

Mots-clés : enhancer,single cell,chromatin accessibility,gene expression,gene regulatory networks,evolution,brain,neuronal diversity,drosophila,mouse,octopus,chicken,massively parallel reporter assay,enhancer design,transcription factors,topic modelling,deep learning,machine learning,generative adversarial networks,enhancer modelling,cis regulatory sequence analysis,transcription factor motif analysis,single cell regulatory genomics,synthetic enhancers
Projet ERC : Hibernating_Synapses (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Dementia is an enormous burden on society. Patients require life-long care and there is no cure or symptomatic treatment. At early phases, dementia is closely associated with synaptic degeneration and this correlates well with Tau pathology in >20 Tauopathies. Interestingly, historic observations in hamsters and squirrels show that when they enter into hibernation, they also display Tau pathology and synaptic loss. Pathologists have pointed to these similarities; however, there is an important difference: synaptic loss is progressive in dementia, but reversible in hibernating animals. Capitalizing on recent technological advancements, I will unravel the mechanisms of this remarkable, yet understudied process of synaptic remodeling in hibernation and then use the pathways that reverse synapse loss in hamsters, to counteract Tau-induced synaptic decline in models of dementia. We will achieve these goals by first defining and studying the molecular and cellular drivers of synaptic remodeling during cycles of hibernation. This is based on innovative spatial transcriptomic and synaptic proteome analyses in hamster brains. We will then identify the human homologues of the hamster genes that reverse synaptic loss following hibernation and use a selection strategy in xenotransplanted human neurons and functional assays on custom-designed multielectrode arrays, to isolate genes rescuing Tau-induced neurodegeneration. This approach is bold, but feasible; my lab has a record of accomplishment in synaptic and neurodegeneration research and we already have strong preliminary work implicating specific pre-synaptic pathways in the types of Tau-dependent synaptic remodeling that we will study here. The gain is that we will uncover the mechanisms of a remarkable process of synaptic resilience, and apply this to rescue the synaptic loss in neurodegeneration. This project will define a conceptually new and unexplored class of therapeutic targets to tackle Tau-induced neuronal decline.

Mots-clés : dementia,synapse loss,hamster,induced pluripotent stem cell,hibernation,liquid phase separation of synaptic vesicles,synaptogyrin 3,tau
Projet ERC : ProtMechCell (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Université de Londres — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UoL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2428850.75 €

Mechanical stimuli regulate an increasingly large number of cellular and tissue functions. However, the effect that those macroscopic forces have on the underpinning proteins is poorly understood.  Most of our knowledge of protein dynamics under force is still restricted to in vitro single-molecule experiments. Collectively, these molecular measurements have revealed that, when denatured with force, proteins unfold and stretch along their end-to-end length, following a completely different pathway from that sampled in biochemical denaturation. Yet, we are still lacking fundamental understanding of how mechanical unfolding of proteins occurs in the cell, and how it impacts cellular function. Here, we propose to develop and apply a combination of state-of-the-art mechanical techniques across scales aiming to correlate the nanomechanical properties of proteins measured in vitro with their behaviour in their physiological cellular context.  We will first study how the regulation of protein elasticity –through dynamic force-induced unfolding and refolding, protein binding and post-translational modifications in cryptic sites of key mechanosensors– affects cellular mechanotransduction. We will also examine, using single-cell optogenetic experiments, how the mechanical unfolding of mechanosensitive transcription factors regulate their import rate into the cell nucleus across the nuclear pore complex, and the potential physiological implications.  We will then test the hypothesis that the mechanical stability and local structure of proteins emerge as a general master regulator of their translocation kinetics across pores of varying sizes and functions, including those present in proteasomes, peroxisomes and lysosomes.  Finally, we will harness the natural specificity of the distinct cellular pores to inspire an intracellular force spectrometer to measure changes in the mechanical stability of a single protein under its functional pulling velocity inside the cell.

Mots-clés : mechanobiology,single molecule biophysics,protein nanomechanics,protein dynamics,mechanotransduction,chemical biology
Projet ERC : TROUBGEN (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université de Londres — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UoL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499909.0 €

Fifty years after the term ‘gender’ entered the vocabulary of social scientists, intense contestation about its meaning has broken out, spilling out of the academy into noisy, heated and wounding spats on social media. As the ‘gender wars’ rage, splintering the consensus that once held together feminist engagement in international policy arenas and international development on 'gender equality', TROUBGEN asks: what’s happened, why now and what can be done? TROUBGEN will draw on the PI’s extensive international networks formed over thirty years of scholarship and engagement and on an international team of advisors and collaborators to establish node points from which to begin a snowballing enquiry into the trouble with gender. It will explore the genealogies of different understandings, situating key thinkers, actors and networks of influence of the concept of 'gender' in international development - including Judith Butler, whose 1990 book Gender Trouble (from which this project takes its title) had such a catalytic effect. It will map the fault-lines of current disputes, examining their genesis, trajectories and encroachments in international development. It will analyse online/offline debates, untangling threads of meaning. It will create Dialogue on Gender spaces to convene and mediate deliberations that enquire into the differences that have now become so toxic and explosive, including devising a poly-vocal Verbatim theatre piece that uses the liminal space of the theatre to bring different perspectives into dialogue, and a Landscapes of Gender exhibition using the creative arts to visualise different strands, threads and meanings. It will evaluate the use of these dialogic and creative methodologies for bridge-work that might make visible and amplify common ground and build greater empathy and understanding amongst those for whom this has become a source of irresolvable ontological difference, threat and injury.

Mots-clés : gender feminism
Projet ERC : CHIRAX (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : AREA Science Park — Pays : Italie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2241938.0 €

The purpose of this proposal is to implement X-ray circular and helical dichroism to investigate the structure and chemical dynamics of molecular systems in solution. The proposal entails first establishing the concepts and observables of X-ray dichroism in steady-state studies both in the soft and hard X-ray ranges, and then implementing time-resolved X-ray circular and helical dichroism spectroscopies as probes of the chemical dynamics.

Mots-clés : chirality,x rays,circular dichroism,helical dichroism,molecular structure,chemical dynamics,liquid solutions,time resolved studies,synchrotrons,x ray free electron lasers
Projet ERC : CONFINED (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université du Cap — Pays : Afrique du Sud — Rôle : Partner
Acronyme de l'entité : UCT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 115982.5 €

CONFINED will develop and validate an innovative, comparative, and global research agenda of confined lives. Confinement is a ubiquitous and unequally distributed human condition. While confinement sometimes can be protective, for some groups, not least the displaced on dangerous roads, the marginalized in urban slums and the detained in prisons, it can be a damaging experience linked to violence and inequality. With an empirical point of departure in different contexts across the global north and south, known to produce a variety of confined lives, CONFINED explores, 1) how certain people’s lives are rendered confineable; 2) how confineable groups and networks navigate discursive, actual, and potential practices of confinement, and 3) how and to what extent the concept of confined lives can transform our understanding of the practices and experiences of confinement across global divides in ways that drive theoretical innovation and help build new agendas for social justice. Through three interdependent and sequentially organized work packages, CONFINED proposes to explore confined lives contextually and ethnographically across the global North and South (WP1); to compare what confines people, how they make sense of their confined lives, and how they navigate confinement (WP2), and to conceptually develop and validate the approach through engagement with academics and experts locally and globally (WP3). CONFINED will carry out comparative, ethnographic field work to follow precariously situated translocal family network across four contexts as a privileged lens to understanding confined lives at the intersection of dangerous journeys, urban slums and prisons and camps: Denmark and Lebanon; South Africa and Malawi; Thailand and Myanmar and the UK and Sierra Leone. This will allow CONFINED to reframe the empirical field of confined lives and to generate a new conceptual language to understand one of the most important drivers of inequality world-wide.

Mots-clés : displacement,urban marginality,incarceration,family and kinship,state and non state violence