Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RADIALIS (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Institut Karolinska — Pays : Suède — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 535155.0 €

In exciting preliminary experiments leveraging our GPSeq method we discovered that the genome of mammalian cells in interphase folds into a steep radial gradient of guanine and cytosine (GC) density, which seems to persist at the level of individual mitotic chromosomes. However, we still lack a fundamental understanding of how this higher-order 3D genome architecture is established and what its functional implications are. Here, I go beyond the state-of-the-art and propose that the observed steep radial GC-gradient is a universal design principle of the radial arrangement of the genome in the nucleus—which I call the radiality principle—that provides a biophysical framework for spatially orchestrating key nuclear processes, beyond gene expression regulation. To test this hypothesis, in this project I pursue five Objectives: (1) First, we develop a novel approach (GP-C) for high-resolution single-cell 3D genome reconstructions to study whether the radial GC-gradient is indeed a universal property of nuclei across different species and cell types. (2) Next, we apply GP-C together with RNA-seq to monitor genome radiality and concurrent gene expression changes as cells undergo karyotype rewiring or significant epigenetic perturbations. (3) In parallel, we develop innovative approaches to probe the internal structure of mitotic chromosomes and model how genome radiality is reorganized as cells traverse mitosis. (4) We then expand our preliminary finding of large-scale DNA-RNA contact hubs that seem to shape cell-type specific radiality landscapes by opposing the radial GC-gradient. (5) Finally, we pioneer methods for profiling nuclear proteins radially and apply them to test the bold hypothesis that the radiality principle provides a blueprint for organizing numerous nuclear processes. This project aims at conclusively addressing long-standing questions in the field of 3D genome biology and proposes novel mechanisms of nuclear function regulation.

Mots-clés : 3d genome organization chromosomes mitosis dna rna contacts transcription factors fluorescence in situ hybridization high throughput sequencing
Projet ERC : SecretAutism (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997729.0 €

Since the ancient Egyptians, the fluid in the brain has been considered a product of spirits, a pathological signature or inert liquid. Even at the turn of the 19th century, when the cerebrospinal fluid (CSF) was first described as a physiological substance, the CSF and the interstitial fluid (ISF), the fluid surrounding all the cells of the brain, were considered solely as a cushion. Only more recently studies have begun to show that the compositions of these fluids can have a marked impact on brain development and animal behaviour. A number of studies have employed omics to demonstrate that the ISF and the CSF are rich in secreted proteins, RNAs and metabolites. However, it is still unclear how these factors influence the development and the function of the brain. Here, we will take a systematic approach to advance our knowledge about the role of extracellular proteins in the brain in health and disease. Using knowhow in studying the causes of autism spectrum disorders (ASDs) my lab will study the effects of changes in the composition of the extracellular space of the brain at unprecedented resolution and scale. Specifically, we aim to 1) functionally identify proteins of the extracellular space that modulate neural development; 2) study proteins that are packaged into extracellular vesicles and whose mutations are considered high ASD-risk factors; 3) analyse -in vivo- the function of HNRNP U, an RNA-binding protein, which we identified in brain extracellular vesicles and whose mutations are tightly linked to neurodevelopmental disorders. This endeavour will represent an important step toward a better understanding of the role of extracellular factors in brain development and function. My work will highlight an entire class of protein encoding genes that crucially contribute to neural development by a previously underappreciated pathway, i.e. through the extracellular parenchyma and that when altered lead to forms of ASDs which may be more amenable to treatment.

Mots-clés : autism spectrum disorders,extracellular proteome
Projet ERC : ChromaDYN (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1850000.0 €

Chromatin packages the eukaryotic genome in a highly dynamic fashion, with dramatic structural changes during every cell cycle. At the same time, chromatin provides remarkable stability for transcriptional regulation and genome organization, for example in maintaining gene expression programs and lineage identity during complex organismal development. A mechanism to propagate information through ‘disruptive’ transitions in the cell cycle, namely DNA replication and mitosis, is key in maintaining heritable, so-called ‘epigenetic’ chromatin states.  Proteins that build and interact with chromatin, foremost histones, are much more than static architectural components. This motivates the development of time-resolved quantitative assays in the living cell, which will allow to capture dynamic features of chromatin states over timescales from minutes to days. Building on a synthetic biology toolbox, a quantitative multimodal pulse-and-label strategy will be developed. Following protein populations in both time and subcellular/genomic space, dynamic protein-protein interaction networks and chromatin maps will be captured.  The project will use to state-of-the-art quantitative biochemical, imaging, genomics and proteomics readouts, including single-cell readouts. These will feed into mathematical models to describe the dynamics and potential heterogeneity/stochasticity of the system under study, predict its response to perturbations and guide mechanistic hypotheses. The project will systematically decipher mechanisms for propagating epigenetic chromatin states, starting with the fundamental rules of histone inheritance through replication and mitosis. Additional levels of complexity introduced through chromatin remodeling activities, nucleosome turnover and histone exchange will be integrated. Finally, the dynamics underlying developmental chromatin state transitions, including asymmetric cell fate decisions, will be resolved.

Mots-clés : quantitative epigenomics,quantitative proteomics,chromatin dynamics,epigenetic inheritance,pluripotent stem cells,gene expression regulation,chromatin remodeling,mathematical modeling
Projet ERC : VULCAN (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1965025.0 €

Vulcan, the Roman god of blacksmithing, was revered in Europe since the Iron Age (1200-500 BC) for a powerful skill: controlling the macroscopic properties of metals (strength, ductility, toughness). To this day, thermal treatments such as annealing - cycles of high temperatures, alternated with slow cooling - remain an essential tool of material science. However, Vulcan’s traditional powers forge monolithic, static, and passive materials, and are laughably blunt instruments when compared to living materials, which dynamically reconfigure, repair, and rebuild themselves. Living systems provide proof-of-concepts for what can be achieved: assembling functional materials from elementary blocks that consume fuel. VULCAN: matter, powered from within, takes forging into the modern age, injecting energy directly through active agents present in the materials. It is experiment-driven and bottom-up, establishing novel experimental strategies to fabricate materials powered from within, with phases and structures that cannot be achieved via thermal treatments, and present non-conventional mechanical and rheological properties (self-healing, odd viscosities). The proposal notably aims to control the phase diagram of matter with spatiotemporal modulation of activity of the bath. We will devise an active bath of swimming bacteria to assemble macroscopic and 3D colloidal crystals and gels [Objective 1], with structures and at scales that cannot be achieved thermally. In parallel, we will devise exotic condensed phases of matter: 2D liquids of spinners and networks of active beams [Objective 2], made from large numbers of autonomous micromachines built from light-activated colloids. This is uncharted territory and an ambitious and high-risk goal, fueling VULCAN’s lasting impact – tearing down the boundary between Active Matter and Materials Science - and opening the path to a new class of materials, powered from within, with applications in (bio)engineering and photonics.

Mots-clés : active matter colloidal assembly
Projet ERC : DOPAGE (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 800000.0 €

Many older adults experience impairment of cognitive functions, such as memory. While changes to the aging brain are often assumed to underlie cognitive decline, but it has turned out surprisingly hard to identify coupled brain-cognitive changes in aging. This challenge is magnified when searching for potentially modifiable brain alterations that could serve as targets for various kinds of interventions. A promising candidate mechanism is age-related alterations in neurotransmitters like dopamine (DA) and noradrenaline (NA), crucial for brain functions. Yet, existing models of aging related to DA and NA are inadequate, as past studies solely focused on either the DA or NA system and also emphasized a single facet of the multifaceted DA system (either pre- or post-synaptic). This represents a serious omission because various parts of the DA system are tightly regulated and the balance between pre- and post-synaptic markers, rather than each marker in isolation, might be more critical for efficient neuromodulatory function. Contrary to the prevailing notion of a global DA neurodegeneration, characterized by a hypodopaminergic condition, I hypothesis that aging is accompanied with loss of balance between pre- and post-synaptic DA systems. This imbalance holds profound implication for functional brain integrity and cognitive decline in aging. The overarching goal of this ground-breaking research program is to, for the first time, address the fundamental question of how the dynamic interplay between pre- and post-synaptic markers of the DA, along with its interaction with equally critical NA, evolves as individuals age and how these dynamics are linked to functional brain integrity and cognitive decline. Of particular interest is whether transiently restoring the balance between pre- and post-synaptic components of the DA system and NA through pharmacological intervention, opens a window to remodel the aging brain and improve cognitive function in some older individuals.

Mots-clés : pet,mri,dopamine,aging,cognition
Projet ERC : GaMe (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Research Institute of Molecular Pathology — Pays : Autriche — Rôle : PI
Acronyme de l'entité : IMP
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2000000.0 €

The life of every sexually reproducing being can be traced back to a singular event: the fusion of sperm and egg. Gamete fusion is perhaps the most critical step in the process of fertilization. However, the mechanisms underlying vertebrate sperm-egg fusion and the events that precede it (sperm-egg recognition) are largely unknown. Uncovering the molecular machinery and biophysical mechanisms mediating sperm-egg recognition and membrane fusion in vertebrates is therefore one of the biggest challenges in fertilization research. In this project we aim to uncover the mechanistic principles of vertebrate fertilization by exploiting the unique advantages of zebrafish as a vertebrate model in combination with in vitro reconstitution assays. We will focus on two main questions:  1) What is the molecular mechanism of sperm-egg recognition? 2) What are the molecular and biophysical principles underlying sperm-egg fusion?  To identify new essential components of the sperm-egg recognition and fusion machineries, we will develop candidate and unbiased screening approaches. We will combine functional studies in vivo, using phenotypic, genetic, biochemical, and advanced high-resolution imaging approaches, with mechanistic studies in vitro, using structural and reconstitution assays, to rigorously determine requirement and sufficiency, causal relationships, spatiotemporal dynamics and mechanisms. Our recently discovered fertility factors Bouncer (sperm-egg recognition) and Dcst1/2 (sperm-egg fusion) provide precise entry points for screens and for functional and mechanistic studies. Overall, our goal is to mechanistically understand how sperm and egg recognize and bind to each other, and how their membranes subsequently fuse. The insights gained will form the basis for our ultimate vision, to reconstitute a functional ‘fertilization interface’ in vitro, and by these means understand one of the most fundamental processes of life.

Mots-clés : fertilization,cell cell fusion,sperm,egg,zebrafish,in vitro reconstitution
Projet ERC : ID-COMPRESSION (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université de Limerick — Pays : Irlande — Rôle : PI
Acronyme de l'entité : UL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999980.0 €

The breakthrough to be pursued in ID-COMPRESSION is that social polarization is information compressibility, where attitudes provide redundant information about group membership. ID-COMPRESSION proposes that a polarized social information system is a socially comprehensible one, where it is easy to categorize people into groups and identify social outliers. Since comprehensibility depends on regularities, this will consequently be a compressible social information system. If successful, this radical theory of social normativity will explain how: (1) social identity becomes embedded in social information via social interaction; (2) information thereby becomes comprehensible in social identity terms; (3) comprehensibility of identity-laden social information is a form of information compressibility; (4) compressibility facilitates group processes, making positions comprehensible and socially meaningful; (5) the structure of the social information system provides conversion pathways, where (a) the probability of someone taking a new position depends on the ones they already hold, (b) taking a new position shifts the holder’s identity and makes a new range of positions accessible, (c) chains of transition probabilities form pathways through the identity-information space, and (d) the structured social information system is dynamically constituted by the positions expressed by the people within it. (6) Compressible social information systems are ripe for pernicious polarization, particularly in situations of intergroup threat, affective polarization, or zero-sum outcomes. (7) Social media interlocks with psychosocial processes in ways that can accelerate pernicious polarization. This radical new understanding of social normativity will show how social identity dynamically interfaces with social information, allowing us to understand how important social issues (e.g. climate change; global health crises) become identity-charged and polarized.

Mots-clés : polarization information theory compression social identity social psychology comprehensibility
Projet ERC : CanopyChange (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université de Gand — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999094.0 €

Tree canopies are one of the most recognizable features of forests, providing shelter from external influences to a myriad of species that live in the understorey. Canopy disturbances are now accelerating across European forests, and climate-change induced drought is a key driver. These disturbances are opening the canopy and exposing forest biodiversity to no-analog light regimes and drought – light and drought levels they have never been exposed to before. As the majority of forest plant species occur in the shade below tree canopies, the combination of altered light regimes and intensifying droughts can strongly impact forest biodiversity. However, the interactive effects of novel light regimes and drought on temperate forest biodiversity have never been investigated before. Since recent European droughts are unprecedented in the last two millennia, and this has initiated the largest pulse of forest disturbances in almost two centuries, the time to assess impacts on biodiversity is now. The overarching aim of CanopyChange is to quantify, understand and predict the impacts of no-analog light regimes and drought on below-canopy forest plant biodiversity. To address this challenging goal, cross-continental resurveyed vegetation plots, the first pan-European forest disturbance-drought experiment, and a pioneering canopy clipping mesocosm experiment will be combined with an interdisciplinary toolbox drawing from ecology, forestry, and climatology. These data will then feed into cutting-edge joint species distribution models to project European forest plant biodiversity responses to future climate and canopy change. CanopyChange will be the first integrative study of pan-European forest plant biodiversity responses to no-analog light regimes and drought. CanopyChange is at the heart of biodiversity conservation and forest management, and will deliver much-needed information for policy makers and managers to adapt to the future, no-analog conditions in European forests.

Mots-clés : climate change,forest biodiversity,conservation,understorey plants,drought,modelling
Projet ERC : EMERGE (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Gand — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1943750.0 €

Rule of law and human rights are under pressure worldwide. The political and legal landscape is dramatically changing, with situations of crisis becoming a recurrent presence in the life of our polities. We thus witness a resurgence of emergency legislation and measures that states employ to tackle the nefarious effects caused by numerous disruptions: from financial instability to terrorist activity, pandemics, or military threat. Traditionally, emergency has been understood as a mechanism that has only temporary and limited effects on legal systems: once the crisis recedes, fundamental rights and constitutional process are restored. EMERGE argues that emergency has long-lasting effects subsisting the crisis. They affect our understanding of human rights, the rule of law principle and constitutional practices. EMERGE will advance a paradigmatic shift in the study of emergency by offering an original re-evaluation of the impact emergency has on the operation of the law. It will provide a much-needed legal historical explanation of how the historical experience of emergency has shaped constitutional and political cultures across Europe in the past century. Delivering a chronological examination and a timeline of the practice of emergency in relation to economic, social and political crises it will critically re-evaluate key moments in European constitutional history from 1914 to 2020. EMERGE will offer a comprehensive analysis of emergency by forging a unique multidisciplinary approach drawing on comparative legal history (contextual legal history), legal theory (law in action, law in context, narrative jurisprudence) and digital humanities (similarity, network and sentiment analysis). Rather than focusing exclusively on legal rules, it will study the agency of individuals, actors and subjects of emergency legislation and reconfigure emergency as a multi-layered socio-legal phenomenon involving social actors and political choices shaping constitutional cultures.

Mots-clés : comparative law constitutional law emergency human rights judicial independence legal history legal theory rule of law