Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CMTaaRS (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Familial forms of neurodegenerative diseases are caused by mutations in a single gene. It is unknown whether distinct mutations in the same gene or in functionally related genes cause disease through similar or disparate mechanisms. Furthermore, the precise molecular mechanisms underlying virtually all neurodegenerative disorders are poorly understood, and effective treatments are typically lacking. This is also the case for Charcot-Marie-Tooth (CMT) peripheral neuropathy caused by mutations in five distinct tRNA synthetase (aaRS) genes. We previously generated Drosophila CMT-aaRS models and used a novel method for cell-type-specific labeling of newly synthesized proteins in vivo to show that impaired protein translation may represent a common pathogenic mechanism. In this proposal, I aim to determine whether translation is also inhibited in CMT-aaRS mouse models, and whether all mutations cause disease through gain-of-toxic-function, or alternatively, whether some mutations act through a dominant-negative mechanism. In addition, I will evaluate whether all CMT-aaRS mutant proteins inhibit translation, and I will test the hypothesis, raised by our unpublished preliminary data shown here, that a defect in the transfer of the (aminoacylated) tRNA from the mutant synthetase to elongation factor eEF1A is the molecular mechanism underlying CMT-aaRS. Finally, I will validate the identified molecular mechanism in CMT-aaRS mouse models, as the most disease-relevant mammalian model. I expect to elucidate whether all CMT-aaRS mutations cause disease through a common molecular mechanism that involves inhibition of translation. This is of key importance from a therapeutic perspective, as a common pathogenic mechanism allows for a unified therapeutic approach. Furthermore, this proposal has the potential to unravel the detailed molecular mechanism underlying CMT-aaRS, what would constitute a breakthrough and a requirement for rational drug design for this incurable disease.

Mots-clés : peripheral neuropathy,trna synthetase,non canonical amino acid tagging,drosophila genetics,mouse genetics
Projet ERC : FLDcure (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149800.0 €

Fatty Liver disease (FLD) is a widespread disease which can often progress to Nonalcoholic steatohepatitis, cirrhosis and liver cancer. At present FLD disease affects a huge perportion of the population and prompt treatment will be of major health benefits to the general population. We have developed a specific therapeutic targeting a microRNA we and others have shown to be involved in the pathogenesis of FLD. This therapeutic agent can dramatically reduce FLD in a mouse model. We would like to extend the pre-clinical studies in order to encourage interest of a pharmaceutical company who will license the technology and pursue clinical trials.

Mots-clés : nonalcoholic fatty liver disease,microrna,nafld,nash
Projet ERC : LawsOfSocRep (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : IFMR Graduate School of Business — Pays : Inde — Rôle : Partner
Acronyme de l'entité : IFMR
Type d'entité : Autres
Financement ERC de l'entité : 327621.75 €

Feminist scholars have long demonstrated the invisibility of women’s reproductive labour, performed in bearing and raising children, maintaining households and socially sustaining male labour. Mainstream international economic institutions acknowledge unpaid care work as an obstacle to women’s economic empowerment. Sustainable Development Goal 5.4 requires that unpaid care and domestic work be recognised through provision of public services and shared responsibility in the family. However the world faces a growing care deficit even as states and international institutions fail to commit to systemic reforms and criminalise women’s economic choices. Anchored in the global South context of India, the project offers a cutting-edge, inter-disciplinary lens to retheorise the normative, empirical, regulatory and policy dimensions of the law’s regulation of social reproduction. The project broadly conceptualises female reproductive labour to include unpaid domestic work as well as sex work, erotic dancing, commercial surrogacy and paid domestic work. Placing varied forms of reproductive labour along the market-marriage continuum, the proposed project offers four main work packages: (1) Normative: Articulates a materialist feminist theory of reproductive labour, revitalises feminist legal theory on the economy through a distributional analysis of the laws of social reproduction (2) Empirical: Consolidates and supplements through new empirical research the study of the political economies and legal ethnographies of sex work, bar dancing, commercial surrogacy and paid domestic work to improve women’s economic bargaining power (3) Regulatory/Policy: Catalogues for each sector innovative economic models, legal and governance tools, policy proposals (including local experimental measures and radical blue-sky ideas) to enhance women’s economic bargaining power and (4) Political Impact: Shifts political sensibilities by dissolving discursive and policy silos between these sectors.

Mots-clés : feminist theory,india,women s labour
Projet ERC : DEEPMED (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Universidad de Sevilla — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1858541.0 €

Few geographical spaces have been more relevant to human life and more intensively theorized than the Mediterranean Sea. Today, this sea poses some of the most pressing challenges and opportunities for European economic, security, and environmental policies. Answers to how to manage the region depend on ideas and perceptions of integration and division of the basin and its peoples. But the Mediterranean as a spatial concept has radically changed in the last 160 years as humans have gained access to its depths, unveiling an underwater world to discover, exploit, and navigate. The Mediterranean has become a volume. DEEPMED is the first historical account of the discovery of the deep Mediterranean environment. Its main hypothesis is that science and strategy jointly made the Mediterranean depths into an object of analysis and a political space, which in turn shaped science and strategy in the region. DEEPMED pursues three specific objectives: 1) identifying the actors and contexts that enabled perceptions and practices of depth in the Med; 2) describing how natural and human time-scales interact in this body of water, and 3) tracking key conceptual landmarks defining the uniqueness and representativeness of the Mediterranean volume vis à vis the global ocean. DEEPMED is the first basin-scale step in a novel approach to oceanic history that incorporates analyses of deep and bottom layers of the Sea to gauge the causes and effects of the historical emergence of depth. This requires an innovative interdisciplinary, transnational and digital methodology. The project identifies overarching trajectories of human engagement with Mediterranean depths from the mid-19th century to the present, including contrasting timelines and perspectives. The availability of digital tools for creating a database that facilitates geospatial and visual analyses make the project timely. The current security and environmental Mediterranean crises make it essential.

Mots-clés : mediterranean,maritime,oceanography,science,technology,strategy,environment,spatial,hgis,global,submarines,acoustics,instruments,infrastructures,resources,borders,climate change
Projet ERC : HistoGenes (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Austrian Academy of Sciences — Pays : Autriche — Rôle : CO-PI
Acronyme de l'entité : OAW
Type d'entité : Recherche
Financement ERC de l'entité : 888357.0 €

Few parts of Europe witnessed so many population shifts in a few centuries as the Carpathian Basin in 400-900 CE. In this macro-region along the middle Danube, Pannonians, Romans, Goths, Gepids, Longobards, Avars, Bulgars, Slavs, Franks and many others came and went. This is an intriguing test case for the relationship between ethnic identities constructed in texts, cultural habitus attested in the archaeological record, and genetic profiles that can now be analysed through ancient DNA. What was the impact of migrations and mobility on the population of the Carpathian Basin? Was the late antique population replaced, did it mix with the newcomers, or did its descendants only adopt new cultural styles? To what degree did biological distinctions correspond to the cultural boundaries and/or ethnonyms in the texts? If pursued with methodological caution, this case study will have implications beyond the field. HistoGenes will analyse c. 6,000 samples from graves with cutting edge scientific methods, and contextualize the interpretation of these data in their archaeological and historical setting. The rapid progress of aDNA analysis and of bio-informatics now make such an enterprise viable. However, the methods of historical interpretation have not kept pace. HistoGenes will, for the first time, unite historians, archaeologists, geneticist, anthropologists, and specialists in bio-informatics, isotope analysis and other scientific methods. Many team members have already collaborated successfully in a pilot project, which has demonstrated the feasibility of the approach and of the integrated workflow at the core of the project. A wide range of particular historical questions will be addressed from an interdisciplinary perspective, and fundamental theoretical and methodological issues can be explored. HistoGenes will not only advance our knowledge about a key period in European history, but also establish new standards for the historical interpretation of genetic data.

Mots-clés : early middle ages,late antiquity,migration,ethnicity,transformation of the roman world,historical method,interdisciplinary method,steppe empires
Projet ERC : HistoGenes (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Hungarian Academy of Sciences — Pays : Hongrie — Rôle : Partner
Acronyme de l'entité : MTA
Type d'entité : Recherche
Financement ERC de l'entité : 885125.0 €

Few parts of Europe witnessed so many population shifts in a few centuries as the Carpathian Basin in 400-900 CE. In this macro-region along the middle Danube, Pannonians, Romans, Goths, Gepids, Longobards, Avars, Bulgars, Slavs, Franks and many others came and went. This is an intriguing test case for the relationship between ethnic identities constructed in texts, cultural habitus attested in the archaeological record, and genetic profiles that can now be analysed through ancient DNA. What was the impact of migrations and mobility on the population of the Carpathian Basin? Was the late antique population replaced, did it mix with the newcomers, or did its descendants only adopt new cultural styles? To what degree did biological distinctions correspond to the cultural boundaries and/or ethnonyms in the texts? If pursued with methodological caution, this case study will have implications beyond the field. HistoGenes will analyse c. 6,000 samples from graves with cutting edge scientific methods, and contextualize the interpretation of these data in their archaeological and historical setting. The rapid progress of aDNA analysis and of bio-informatics now make such an enterprise viable. However, the methods of historical interpretation have not kept pace. HistoGenes will, for the first time, unite historians, archaeologists, geneticist, anthropologists, and specialists in bio-informatics, isotope analysis and other scientific methods. Many team members have already collaborated successfully in a pilot project, which has demonstrated the feasibility of the approach and of the integrated workflow at the core of the project. A wide range of particular historical questions will be addressed from an interdisciplinary perspective, and fundamental theoretical and methodological issues can be explored. HistoGenes will not only advance our knowledge about a key period in European history, but also establish new standards for the historical interpretation of genetic data.

Mots-clés : early middle ages,late antiquity,migration,ethnicity,transformation of the roman world,historical method,interdisciplinary method,steppe empires
Projet ERC : HistoGenes (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Institute for advanced study - louis bamberger and mrs felix fuld foundation corporation — Pays : Etats-Unis — Rôle : PI
Acronyme de l'entité : Ias
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1170887.0 €

Few parts of Europe witnessed so many population shifts in a few centuries as the Carpathian Basin in 400-900 CE. In this macro-region along the middle Danube, Pannonians, Romans, Goths, Gepids, Longobards, Avars, Bulgars, Slavs, Franks and many others came and went. This is an intriguing test case for the relationship between ethnic identities constructed in texts, cultural habitus attested in the archaeological record, and genetic profiles that can now be analysed through ancient DNA. What was the impact of migrations and mobility on the population of the Carpathian Basin? Was the late antique population replaced, did it mix with the newcomers, or did its descendants only adopt new cultural styles? To what degree did biological distinctions correspond to the cultural boundaries and/or ethnonyms in the texts? If pursued with methodological caution, this case study will have implications beyond the field. HistoGenes will analyse c. 6,000 samples from graves with cutting edge scientific methods, and contextualize the interpretation of these data in their archaeological and historical setting. The rapid progress of aDNA analysis and of bio-informatics now make such an enterprise viable. However, the methods of historical interpretation have not kept pace. HistoGenes will, for the first time, unite historians, archaeologists, geneticist, anthropologists, and specialists in bio-informatics, isotope analysis and other scientific methods. Many team members have already collaborated successfully in a pilot project, which has demonstrated the feasibility of the approach and of the integrated workflow at the core of the project. A wide range of particular historical questions will be addressed from an interdisciplinary perspective, and fundamental theoretical and methodological issues can be explored. HistoGenes will not only advance our knowledge about a key period in European history, but also establish new standards for the historical interpretation of genetic data.

Mots-clés : early middle ages,late antiquity,migration,ethnicity,transformation of the roman world,historical method,interdisciplinary method,steppe empires
Projet ERC : DOIIF (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : PI
Acronyme de l'entité : KI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Fibrosis in response to tissue damage or persistent inflammation is a pathological hallmark of many chronic degenerative diseases where Idiopathic Pulmonary Fibrosis (IPF) is one of the most severe diseases. IPF is a progressive condition with unknown etiology and a median survival of three years from diagnosis. Current medical treatment is limited to slowing down the disease and thus there is still a high unmet medical need. OGG1 enzyme has a major role in DNA repair in conditions of oxidative stress and also in regulation of gene transcription involved in immune responses. In our ERC grant we developed a first-in class OGG1 inhibitor that protects from exaggerated immune response induced by the proinflammatory mediator TNFα. We have shown with this compound in several airway inflammation models, that inhibition of OGG1 results in a significant down regulation of mediators associated with inflammation and fibrosis, reduced infiltration of immune cells in lungs and increased alveolar integrity compared with control. We have developed a large number of compounds and in this proposal we aim to demonstrate proof of concept (PoC) for the most promising compound in an established model of pulmonary fibrotic diseases in order to select a candidate drug (CD). Our plan is to establish collaboration with industrial partners for further development in order take one compound through preclinical development and clinical phase 1/2a for further commercialization. Treatment with a potent OGG1 inhibitor has the potential to attenuate or resolve the progress of the disease, alone or in combination with existing therapies and increase survival of IPF patients and reduce healthcare costs.

Mots-clés : ogg1 inhibitor,small molecules,inflammation,fibrosis,drug development
Projet ERC : AsthmaPhenotypes (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 269141.0 €

Fifteen years ago it was widely believed that asthma was an allergic/atopic disease caused by allergen exposure in infancy; this produced atopic sensitization and continued exposure resulted in eosinophilic airways inflammation, bronchial hyper-responsiveness and reversible airflow obstruction. It is now clear that this model is at best incomplete. Less than one-half of asthma cases involve allergic (atopic) mechanisms, and most asthma in low-and-middle income countries is non-atopic. Westernization may be contributing to the global increases in asthma prevalence, but this process appears to involve changes in asthma susceptibility rather than increased exposure to “established” asthma risk factors. Understanding why these changes are occurring is essential in order to halt the growing global asthma epidemic.This will require a combination of epidemiological, clinical and basic science studies in a variety of environments. A key task is to reclassify asthma phenotypes. These are important to: (i) better understand the aetiological mechanisms of asthma; (ii) identify new causes; and (iii) identify new therapeutic measures. There are major opportunities to address these issues using new techniques for sample collection from the airways (sputum induction, nasal lavage), new methods of analysis (microbiome, epigenetics), and new bioinformatics methods for integrating data from multiple sources and levels. There is an unprecedented potential to go beyond the old atopic/non-atopic categorization of phenotypes. I will therefore conduct analyses to re-examine and reclassify asthma phenotypes. The key features are the inclusion of: (i) both high and low prevalence centres from both high income countries and low-and-middle income countries; (ii) much more detailed biomarker information than has been used for previous studies of asthma phenotypes; and (iii) new bioinformatics methods for integrating data from multiple sources and levels.

Mots-clés : asthma,epidemiology,phenotypes
Projet ERC : AsthmaPhenotypes (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 30093.0 €

Fifteen years ago it was widely believed that asthma was an allergic/atopic disease caused by allergen exposure in infancy; this produced atopic sensitization and continued exposure resulted in eosinophilic airways inflammation, bronchial hyper-responsiveness and reversible airflow obstruction. It is now clear that this model is at best incomplete. Less than one-half of asthma cases involve allergic (atopic) mechanisms, and most asthma in low-and-middle income countries is non-atopic. Westernization may be contributing to the global increases in asthma prevalence, but this process appears to involve changes in asthma susceptibility rather than increased exposure to “established” asthma risk factors. Understanding why these changes are occurring is essential in order to halt the growing global asthma epidemic.This will require a combination of epidemiological, clinical and basic science studies in a variety of environments. A key task is to reclassify asthma phenotypes. These are important to: (i) better understand the aetiological mechanisms of asthma; (ii) identify new causes; and (iii) identify new therapeutic measures. There are major opportunities to address these issues using new techniques for sample collection from the airways (sputum induction, nasal lavage), new methods of analysis (microbiome, epigenetics), and new bioinformatics methods for integrating data from multiple sources and levels. There is an unprecedented potential to go beyond the old atopic/non-atopic categorization of phenotypes. I will therefore conduct analyses to re-examine and reclassify asthma phenotypes. The key features are the inclusion of: (i) both high and low prevalence centres from both high income countries and low-and-middle income countries; (ii) much more detailed biomarker information than has been used for previous studies of asthma phenotypes; and (iii) new bioinformatics methods for integrating data from multiple sources and levels.

Mots-clés : asthma,epidemiology,phenotypes