Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RNAEPIGEN (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1791250.0 €

Epigenetic mechanisms are considered to be central to the development of multicellular organisms made of different cell types, all having identical genomes. Similarly, they may explain how genetically identical organisms are capable of adapting to distinct environmental conditions. Yet, the molecular mechanisms regulating how epigenetic traits can be inherited during cell division or across generations are not fully understood. Using the nematode Caenorhabditis elegans, we have recently revealed how the nuclear Argonaute protein CSR-1 and its associated short RNAs participate in global transcriptional regulation and chromatin organization. This unprecedented observation opened up a new class of molecular mechanisms by which Argonaute proteins and their bound short RNAs may actively contribute to epigenetic inheritance in animals. This research proposal focuses on the characterization of short-RNA-based mechanisms of epigenetic inheritance during animal development and upon environmental changes. Using C. elegans as an animal model system, we plan to integrate genetic, biochemical, and molecular biology tools with high-throughput genomic and proteomic approaches to dissect (i) the molecular mechanism by which CSR-1-bound short RNAs regulate transcription, (ii) test their ability in propagating the memory of actively transcribed genomic regions during early embryonic development, and (iii) characterize their role in propagating the memory of stress responses across generations to facilitate the adaptation of animals to environmental changes. Given the association of nuclear Argonaute proteins with transcriptionally active loci in metazoans, we anticipate that similar CSR-1-like epigenetic functions are also conserved in humans. Therefore, our research has the potential to significantly advance our understanding of the molecular mechanisms underlying epigenetic inheritance and reveals their impact on animal development and adaptation to changing environments.

Mots-clés : short rnas,small rnas,sirnas,endo sirnas,rnai,rna silencing,epigenetics,transcriptional regulation,rna biology,chromatin,histone modifications,c  elegans,epigenetic inheritance
Projet ERC : Epilepsy_Core (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Epilepsy burdens 1% of the population. Brain surgery can cure seizures and stop cognitive decline, but it is complex and often unsuccessful. I aim to advance cure from epileptic brain disease radically by 1) pinpointing the core of epilepsy and 2) understanding the effects on normal brain functioning. High-frequency oscillations (HFOs) are novel markers of the core of focal epilepsy, discovered in long-term invasive EEG. I initiated direct HFO-based guidance of epilepsy surgery with intra-operative invasive electrodes. However, HFOs still appear stochastic epiphenomena. Therefore, I will now uncover the direct microlevel high-frequency EEG reflection of the distorted cortex. I will use three macrolevel signal prerequisites for seizure and HFO generation to innovate intra-operative recording and signal analysis: susceptible (evoke with long-distance electrical stimulation; cross-frequency coupling), sudden (low-noise adhesive electrodes; auto-regression) & spreading (high-density recordings; functional connectivity). I will pilot test technical solutions and optimize analyses with supervised machine learning based on pivotal epileptogenic versus healthy tissue and on postsurgical outcomes. Next, I will explore the broad effect of epileptic on physiological high frequency brain activity taking cognitive performance as epitome, especially in people without seizures. Current electrocorticography data come from limited, diverse and complex cases with no gold standards for diseased and normal cortex. I will therefore obtain data from 200 otherwise unguided brain surgeries with different levels of epileptogenicity and cognitive impairment: highly epileptogenic tumors (simple), gliomas (many) and meningiomas which compress healthy brain (uniform; partly without seizures). I will integrate techniques in a neurosurgical real-time recording and projecting device that simplifies finding and removing epileptogenic tissue to stop the distorting effect in focal brain disorders.

Mots-clés : epilepsy,glioma,meningeoma,brain surgery,cognition
Projet ERC : GALVANI (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Université de Rennes — Pays : France — Rôle : Partner
Acronyme de l'entité : UNIVRENNES
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 128520.0 €

Epilepsy is a neurological disorder affecting 65 million people worldwide. Pharmacological treatments or surgery are ineffective in one third of the cases – 19 million people. Recent findings indicate that non-invasive brain transcranial current stimulation (tCS) is safe and of therapeutic promise in epilepsy. However, it is not yet indicated as a standard treatment due to major scientific limitations: unknown mechanisms of action, insufficient account for patient-specific factors, poor understanding of short- and long-term effects. Our ambition is to transform the care of a large fraction of patients living with drug-resistant epilepsies by solving a fundamental problem: to efficiently target and control large-scale epileptic brain networks with tCS-induced neuromodulatory weak electric fields. To proceed, GALVANI’s synergetic research strategy addresses four interdisciplinary challenges: (1) Unravel the intricate relationship between weak electric fields and their neurophysiological effects at the level of neurons, neuronal assemblies and networks; (2) Maximize their therapeutic effects by altering the neurodynamics of patient-specific epileptogenic networks; (3) Develop optimal personalized neuromodulation protocols for novel multichannel tCS technologies; (4) Test optimized protocols in a cohort of patients and objectively define potential responders. The required competences and resources are met in GALVANI, uniting the passion and background of three experts and their teams in biomathematics (computational neuroscience), biophysics (bioelectromagnetism) and medicine (epileptology). The project vision is that critical features of pathological networks can be effectively captured in a new generation of hybrid computational models developed for tailored therapy. The inflection point is to prevent epileptic seizures from a bottom-up mechanistic understanding and control of tCS effects. This will entail a paradigm shift in epileptic disorders and beyond.

Mots-clés : epilepsy,therapeutic neuromodulation,electric fields,bioelectromagnetism,neurophysiological,models,biophysical models,personalized models,signal processing,optimization,transcranial stimulation,clinical trial
Projet ERC : GALVANI (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : CO-PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 3240111.25 €

Epilepsy is a neurological disorder affecting 65 million people worldwide. Pharmacological treatments or surgery are ineffective in one third of the cases – 19 million people. Recent findings indicate that non-invasive brain transcranial current stimulation (tCS) is safe and of therapeutic promise in epilepsy. However, it is not yet indicated as a standard treatment due to major scientific limitations: unknown mechanisms of action, insufficient account for patient-specific factors, poor understanding of short- and long-term effects. Our ambition is to transform the care of a large fraction of patients living with drug-resistant epilepsies by solving a fundamental problem: to efficiently target and control large-scale epileptic brain networks with tCS-induced neuromodulatory weak electric fields. To proceed, GALVANI’s synergetic research strategy addresses four interdisciplinary challenges: (1) Unravel the intricate relationship between weak electric fields and their neurophysiological effects at the level of neurons, neuronal assemblies and networks; (2) Maximize their therapeutic effects by altering the neurodynamics of patient-specific epileptogenic networks; (3) Develop optimal personalized neuromodulation protocols for novel multichannel tCS technologies; (4) Test optimized protocols in a cohort of patients and objectively define potential responders. The required competences and resources are met in GALVANI, uniting the passion and background of three experts and their teams in biomathematics (computational neuroscience), biophysics (bioelectromagnetism) and medicine (epileptology). The project vision is that critical features of pathological networks can be effectively captured in a new generation of hybrid computational models developed for tailored therapy. The inflection point is to prevent epileptic seizures from a bottom-up mechanistic understanding and control of tCS effects. This will entail a paradigm shift in epileptic disorders and beyond.

Mots-clés : epilepsy,therapeutic neuromodulation,electric fields,bioelectromagnetism,neurophysiological,models,biophysical models,personalized models,signal processing,optimization,transcranial stimulation,clinical trial
Projet ERC : MolCellTissMech (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Epithelial monolayers are amongst the simplest tissues in the body, yet they play fundamental roles in adult organisms where they separate the internal environment from the external environment and in development when the intrinsic forces generated by cells within the monolayer drive tissue morphogenesis. The mechanics of these simple tissues is dictated by the cytoskeletal and adhesive proteins that interface the constituent cells into a tissue-scale mechanical syncitium. Mutations in these proteins lead to diseases with fragilised epithelia. However, a quantitative understanding of how subcellular structures govern monolayer mechanics, how cells sense their mechanical environment and what mechanical forces participate in tissue morphogenesis is lacking. To overcome these challenges, my lab devised a new technique to study the mechanics of load-bearing monolayers under well-controlled mechanical conditions while allowing imaging at subcellular, cellular and tissue resolutions. Using this instrument, my proposal aims to understand the molecular determinants of monolayer mechanics as well as the cellular behaviours that drive tissue morphogenesis. I will focus on four objectives: 1) discover the molecular determinants of monolayer mechanics, 2) characterise monolayer mechanics, 3) dissect how tension is sensed by monolayers, and 4) investigate the biophysics of individual cell behaviours participating in tissue morphogenesis. Together these studies will enable us to understand how monolayer mechanics is affected by changes in single cell behaviour, subcellular organisation, and molecular turnover. This multi-scale characterisation of monolayer mechanics will set the stage for new theoretical descriptions of living tissues involving both molecular-scale phenomena (cytoskeletal turnover, contractility, and protein unfolding) operating on short time-scales and rearrangements due to cell-scale phenomena (cell intercalation, cell division) acting on longer times.

Mots-clés : epithelium,cytoskeleton,f actin,intermediate filaments,adherens junctions,desmosomes,intercellular adhesion,actin cortex,biophysics,cell mechanics,tissue mechanics,optogenetics,fret
Projet ERC : PolarizeMe (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Göttingen — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : GAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1255415.14 €

Epithelial polarity is one of the most fundamental types of cellular organization, and correct cellular polarization is vital for all epithelial tissue. Failure to establish polarity leads to severe phenotypes, from catastrophic developmental deficiencies to life-threatening diseases such as cancer. Despite knowing much about the signalling and trafficking machinery vital for polarity, we lack quantitative knowledge about the intracellular mechanical processes which organize and stabilize epithelial polarity. This presents a critical knowledge gap, as any elaborated understanding of intracellular organization needs to include the forces and viscoelastic mechanical properties that position organelles and proteins. As such, the main aim of POLARIZEME is to determine the intracellular mechanical processes relevant for epithelial polarization, thus providing a mechanical understanding of polarity. We will combine advanced optical tweezers technology with cutting-edge molecular biology tools to rigorously test new intracellular transport concepts such as the active, diffusion-like forces that can position organelles or the recently introduced cortical actin flows that can drag polarity-defining proteins around the cell. Thus we propose (i) to quantify active forces and intracellular mechanics and their relation to organelle positioning, (ii) to quantify polarized cortical and cytoplasmic flows, and (iii) to measure the forces and mechanical obstacles relevant for direct vesicle trafficking. These quantitative biophysics experiments will be supported by mathematical modelling and the development of two new instruments which (a) allow for automated intracellular mechanics measurements over extended time periods and (b) combine multi-view light-sheet microscopy with optical tweezers and UV ablation. Overall, we will provide a new access to understand and describe polarity by merging the physical and biological aspects of its initiation, maintenance and stability.

Mots-clés : cell mechanics,polarity,viscoelastic properties,active fluctuations,cortical flows,optogenetics
Projet ERC : EQUALITY (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Münster — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WWU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1606597.0 €

Equality is one of the main political concerns of our time. Rising economic inequality is often cited as a major reason for the recent rise of political populism. But economic inequality is not the only problem. Inequalities based on gender, race or nationality are also major issues in the contemporary discussion. While most commentators discuss political solutions, the proposed research project analyzes the contributions that courts can make to correct inequalities. Norms protecting equality form part of all major national and international human rights instruments. However, the meaning of equality is fundamentally contested. There is no agreement on what equality exactly means or entails. The question, therefore, is not whether legal equality guarantees can tolerate inequality, but to what extent they can do. Because of these conceptual difficulties, the application of equality and non-discrimination clauses is not a straightforward exercise, in which courts simply apply legal norms to a given set of facts. Instead, courts need to develop doctrinal instruments to give meaning to the concept of equality. The proposed research project analyses how apex courts conceptualize equality in constitutional and international human rights law. It will be based on a comparative study of the equality jurisprudence of 16 jurisdictions and has three aims. Firstly, it intends to create a comparative map of equality jurisprudence, i.e. to describe and categorize the constitutional jurisprudence on equality: Which doctrinal choices do courts make and how do these choices inform the conception of equality? Secondly, it seeks to explain the doctrinal choices of the analyzed courts: Which factors influence courts to arrive at particular conceptions of equality? Thirdly, it has a normative goal and examines whether courts are better suited to correct certain kinds of inequalities than other kinds of inequalities.

Mots-clés : political science,equality,judicial decision making,constitutional review,human rights
Projet ERC : IDENTITIES (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Bologna — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIBO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1990015.0 €

Ethnic and cultural diversity has sharply increased in modern societies due to migration processes. However, the implication of this for adolescents facing the core task of developing their identities are still mostly unknown. For both adolescents without and with a migrant background (e.g., recent refugees, second-generation immigrants) growing up in societies with increasing levels of diversity can be challenging, as they have to manage their identities acknowledging that how they address the core question “who am I?” could be the result of a dynamic process based on multiple and diverse social interactions. The IDENTITIES project adopts a cross-fertilization approach, integrating developmental and social-psychological models, to provide a ground-breaking knowledge on the processes leading to the well-being of adolescents with and without a migrant background. By proposing a multidimensional ecological developmental intergroup perspective, the project aims to examine: (1) how intergroup experiences in ecological contexts (from parents, friends, school, and leisure microsystems to cultural macrosystems) influence the development of adolescents’ (personal, social, and human) identities; (2) how the interplay of identities affects adolescents’ (physical, psychological, and social) well-being; (3) how intergroup experiences in multiple ecological contexts influence adolescents’ well-being disentangling direct and indirect effects (mediated by identities). To achieve these aims, a longitudinal study with 2,250 adolescents from two cohorts will be conducted, including multiple annual, monthly, and daily assessments and applying a multi-informant design (with quantitative data collected from adolescents, parents, teachers, school principals, municipal administrators, archives, and non-invasive medical devices) and it will be complemented by a case study with a narrative approach conducted with 50 adolescents who have lived abroad for at least three months.

Mots-clés : adolescence,development,longitudinal,personal identity,social identity,family,friends,school,leisure contexts,psychological well being,social well being,physical health,diversity,intergroup experiences,migrant background,multi informant
Projet ERC : COMPASS (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Wageningen University & Research — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : WUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1496463.0 €

Eukaryotic Argonaute proteins are known for their central role in RNA interference pathways. Yet, the evolutionary origin of Argonaute proteins lies in prokaryotes, where other proteins essential for RNA interference are absent. Therefore, prokaryotic Argonaute proteins (pAgos) must have distinct ancestral functions. Although a handful of closely related pAgos interfere with exogenous DNA invaders such as plasmids, pAgos are extremely diverse in terms of sequence conservation and domain architecture. In addition, many pAgos genetically associate with various putative enzyme domains, which suggests that they are functionally interdependent. As such, different pAgos must rely on distinct mechanism and are expected to fulfil a range of different roles. Therefore, the function of most pAgos remains completely unknown. The COMPASS project will map the function of unexplored pAgo systems, in which pAgos associate with auxiliary proteins. I hypothesize that in these systems, pAgo binds exogenous DNA sequences in a guide-dependent manner. This can result in the recruitment and/or activation of the auxiliary proteins. As pAgo-associated auxiliary proteins are homologous to proteins involved in DNA recombination, NAD+ turnover, or protein deacetylation, these pAgo systems are expected to fulfil completely novel roles ranging from stimulating horizontal gene transfer to triggering programmed cell death. The uncharacterized roles of these pAgo systems and the mechanisms underlying their functionality will be elucidated by a multidisciplinary approach combining microbiology, protein biochemistry, and X-ray crystallography techniques. Not only will the results facilitate a deeper understanding of the evolutionary diversification of pAgos, it will also enable the repurposing of programmable pAgo systems for the development of genetic tools that facilitate guide sequence-directed DNA recombination and high-sensitivity detection of target DNA sequences.

Mots-clés : argonaute,prokaryotic immune systems,horizontal gene transfer,programmed cell death