Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ParaALPHA (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1659836.0 €

Diabetes is a common disease affecting millions of patients world-vide. The disease is characterised by hyperglycaemia, caused by reduced insulin signalling and release. Recent findings suggest that the hormone glucagon also plays a critical role. Glucagon is a counteregulatory hormone released form alpha cells in pancreatic islets, to increase hepatic glucose production. Diabetic and obese patients suffer from hyperglucagonaemia, which leads to inappropriate hepatic glucose production. Glucagon secretion is regulated by intrinsic and paracrine mechanisms. The intrinsic regulation rely on the effect of glucose on metabolism and the paracrine on secretion of hormones from neighbouring beta and delta cells. Paracrine signalling form insulin and somatostatin inhibits glucagon secretion through activation of Protein kinase B and inhibition of protein kinase A leading to lower electrical and exocytotic activity. Both kinases regulate transcription and metabolism in other tissues. I suggest that paracrine signalling also affect alpha cell metabolism to regulate glucagon secretion. My recent work show that alpha cells rely on fatty acids for ATP production and that the mechanism by which glucose inhibits glucagon secretion requires glucose to lower fatty acid oxidation. In this project, I will 1) investigate whether insulin and somatostatin signalling regulate metabolism and ATP production in alpha cells, 2) identify the underlying kinase signalling, and 3) explore the role of hyperglucagonaemia in diabetes. To understand the effect of insulin and somatostatin on alpha cell function and glucagon secretion, I will use dynamic measurements of kinase signalling, ATP levels, membrane potential and calcium in mouse and human islets. Combining this with genetically modified animal models, we will have the unique opportunity to study if dysfunction of both paracrine and intrinsic regulation of glucagon secretion is required for the development of hyperglucagonaemia in diabetes.

Mots-clés : glucagon secretion,paracrine inhibition,somatostatin,insulin,kinase signalling,glucose metabolism,fatty acid metabolism,islets of langerhans live cell imaging
Projet ERC : SUAHIST (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

A thousand years before Europeans arrived in the Americas, a vast region, covering what is now North-western Mexico and the US Southwest, was inhabited by speakers of languages belonging to the Uto-Aztecan language family. Often described as nomads in a hostile periphery between the cultures of Mesoamerica and the Puebloan cultures of the US Southwest, this project puts the speakers of Southern Uto-Aztecan (SUA) languages at the centre, seeking to achieve two objectives: 1. To recover aspects of ancient SUA people's language and world-view 2. To map cultural and linguistic flows moving through the SUA-sphere in the millennia before European colonization. The project brings to bear the full scope of methods of contemporary historical linguistics: It combines qualitative methods of historical linguistics and narratology with quantitative lexicostatistical and phylogeographic methods to analyse the historical relations between SUA languages, and to analyse developments of SUA mythological traditions. Integrating a component of language documentation, the project works with indigenous scholars and communities to contribute to ongoing efforts of indigenous language maintenance. The project will achieve its two objectives, by undertaking research in three workpackages: WP1 Language Documentation documents the lexicon of two underdocumented SUA languages (Náayeri and Wixárika) creating two new dictionaries. WP2 Qualitative Historical Linguistics uses the dictionaries to build an etymological database of SUA languages and an online database of glossed and annotated mythological texts. It also applies historical comparative analyses to both mythical and lexical data to reconstruct aspects of ancient SUA language and culture. WP3 Quantitative Phylogenetics uses the etymological and mythical databases for phylogenetic and phylogeographic analyses. It pioneers the use of an innovative method for reconciliation of 'word-trees' to produce new phylogenies.

Mots-clés : uto aztecan languages,historical linguistics,mexico,mesoamerica,
Projet ERC : ChroMeta (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

When environment of the embryo changes or when development progresses metabolic reactions are rapidly affected. These alterations to chemical reactions are coupled to epigenetic memory. However, without mechanistic data on how this coupling occurs it is difficult to understand how normal embryogenesis can proceed. This project will elucidate how metabolic changes result in specific epigenetic outcomes and address the function of such regulation. As a model we will use mouse implantation, a process tightly linked to dramatic alterations to chromatin and transcription. We found that this is also associated with extensive metabolic rewiring and that disrupting metabolic flows results in both lineage-specific and mark-specific changes to chromatin. While multiple studies uncovered that metabolism fuels chromatin modifiers with co-factors, the fundamental biological question of how specificity is achieved remains unanswered. Here we will address this challenge by directly testing the three most likely hypotheses: 1) that metabolic reactions shuttle into the nucleus where they specifically fuel chromatin changes; 2) that chromatin-bound metabolic enzymes regulate gene expression and 3) that only specific chromatin modifiers are sensitive to metabolic changes. To address these questions, we will go beyond description as we supplement multi-omic approaches with mechanistic experiments both in vitro and in vivo. Firstly, will use perturbations of nuclear metabolic enzymes and their chromatin binding. Secondly, we will implement protein engineering to render chromatin modifiers resistant to the availability of their co-factors. By uncoupling epi-metabolic regulation, we seek not only to uncover its importance for controlling chromatin states but also the implantation developmental program. This project will form a framework of how future studies can mechanistically unravel intertwined regulatory processes and assess the role of environment and nutrition in early pregnancy.

Mots-clés : heterochromatin,polycomb,implantation,blastocyst,dna methylation,histone modification
Projet ERC : ExplainYourself (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498616.0 €

ExplainYourself proposes to study explainable automatic fact checking, the task of automatically predicting the veracity of textual claims using machine learning (ML) methods, while also producing explanations about how the model arrived at the prediction. Automatic fact checking methods often use opaque deep neural network models, whose inner workings cannot easily be explained. Especially for complex tasks such as automatic fact checking, this hinders greater adoption, as it is unclear to users when the models' predictions can be trusted. Existing explainable ML methods partly overcome this by reducing the task of explanation generation to highlighting the right rationale. While a good first step, this does not fully explain how a ML model arrived at a prediction. For knowledge intensive natural language understanding (NLU) tasks such as fact checking, a ML model needs to learn complex relationships between the claim, multiple evidence documents, and common sense knowledge in addition to retrieving the right evidence. There is currently no explainability method that aims to illuminate this highly complex process. In addition, existing approaches are unable to produce diverse explanations, geared towards users with different information needs. ExplainYourself radically departs from existing work in proposing methods for explainable fact checking that more accurately reflect how fact checking models make decisions, and are useful to diverse groups of end users. It is expected that these innovations will apply to explanation generation for other knowledge-intensive NLU tasks, such as question answering or entity linking. To achieve this, ExplainYourself builds on my pioneering work on explainable fact checking as well as my interdisciplinary expertise.

Mots-clés : explainable ai,automatic fact checking,natural language generation,personalised machine learning,human computer interaction
Projet ERC : LOBBYMETRY (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499043.0 €

The LOBBYMETRY project addresses two types of imbalances in lobbying: 1) mobilisation asymmetries, which exclude some actors from the policy debate, and 2) information asymmetries, which empower specific groups in their exchanges with policymakers. The LOBBYMETRY project analyses these asymmetries and their relationship to each other, as well as their effects on the ways in which sectional and public interests feed into policymaking.  The project studies these asymmetries across populations of interest organisations in twelve European countries and at European Union level, as well as within the climate and digital policy fields, that vary strongly in mobilisation asymmetries and constitute areas where well- or ill-informed policies have vast consequences for humanity at large. LOBBYMETRY strives to open the black-box of policymaker-lobbyist information exchange within these areas, develop measures of informational quality and accuracy in lobbying, and evaluate how and when lobbying pulls outcomes away from the public interest.  Methodologically, the project combines cross-country surveys including an AI-aided survey experiment, cross-venue data on 100 issues in climate and digital policy, and different forms of participant observation of the information exchanges between policymakers and interest organisations in i) natural and ii) researcher-controlled settings. This innovative combination of methods will generate unprecedented quantitative and qualitative evidence on lobbyist-policymaker information exchange in varying contexts.  If successful, the project will shed light on a serious blind spot in the state-of-the-art literature: the mechanisms through which lobbying actually informs policies. Its findings will speak to pressing democratic challenges, such as the underrepresentation of citizen interests in digital policy, and the design of institutional interventions to improve consultation practices, lobbying regulation, and the quality of legislation.

Mots-clés : lobbying,public policy,information provision,political mobilisation,digital policy,climate policy,interest representation
Projet ERC : hypomethGENOME (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499995.0 €

Replication in S phase duplicates not only the genome but also the epigenome, to ensure cell identity is propagated and genome stability maintained in daughter cells. Epigenome propagation in development has been understudied due to lack of appropriate methods, even though replication is widely accepted to be a primary vehicle through which programmed epigenetic changes occur in vivo. In mammalian germline development, the epigenome is reprogrammed via impairment of the epigenome maintenance network. By dividing without maintaining core components of the epigenome, primordial germ cells harbor genomes devoid of the crucial repressive mark DNA methylation. Hypomethylation is destabilizing because it de-represses transposable elements. Despite this, oocytes arrest in a hypomethylated state, regaining methylation only in preparation for ovulation as part of puberty. In parallel, two-thirds of the oocyte pool dies around birth in mammals, and the features delineating oocytes that survive this process from those that die are unclear. I propose that hypomethylation is alternately selected for and against across gametogenesis. Specifically, that hypomethylation a positive feature in primordial germ cells but a deleterious feature in the female germline after sex specification. To test this, we will develop novel transgenic mouse models and technologies to study epigenome propagation in vivo, and utilize state-of-the-art sequencing, mass spectrometry, microscopy, and metabolic labelling approaches. By developing a method for tracking DNA molecules and their associated methyl marks across division in live animals and embryos, we will establish an unprecedented technology for understanding epigenome propagation in development. Cumulatively, this work will uncover the functions and consequences of global hypomethylation in the germline, and provide groundbreaking insights into the nature of mitotic and intergenerational epigenetic inheritance in vivo.

Mots-clés : epigenetic reprogramming,dna methylation,primordial germ cells,oocytes,chromatin,epigenome maintenance,gametogenesis,oocyte attrition,nucleoside mass spectrometry,lineage tracing,metabolic labelling,functional genomics,mouse
Projet ERC : ENFIN (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université des sciences économiques de Vienne — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499749.0 €

For all their differences, modern nation-states are both the energy transition leaders and financial leaders of their time. They are also home to our great financial centers (GFCs), and the question of the rise and fall of GFCs is a matter of longstanding debate. Existing explanations struggle to explain the timing and forecasting of the rise and fall of GFCs in a systematic manner. No researcher has connected the dots between energy transitions, financial transitions, the role of financial systems, and the rise and fall of great financial centers. My nontraditional hypothesis is that energy transitions drive financial transitions and GFCs. The core aims of ENFIN are: Create a new field of research integrating elements from comparative institutionalist literature, socio-technological transition research, and research on financial centers. a) Integrate the role of energy transitions in the literature on financial centers. I will use cross-national and cross-temporal comparisons to establish the sequences and relationship between energy transitions and financial transitions. b) Lift the analytical power of socio-technological transition research with regard to the reciprocal logic of low-carbon energy and green finance transitions. I will examine causal mechanisms through inductive process tracing on evidence about the pressures arising from energy transitions on existing financial structures and socio-economic actors’ responses. c) Investigate the role of institutions in the relationship between green-energy transition and future financial leadership. I will conduct σ-convergence analysis to develop a global database to compare green financial standards by countries and a multigroup latent growth curve (LGC) model to compare and predict growth trajectories of multiple groups (e.g., coordinated market economies, capital market economies, and state driven economies) in financial systems over time.

Mots-clés : energy transitions,infrastructure investments,path dependency,financial transitions,innovation,market capitalization,financial systems,great financial centers,green financial centers,green financial standards
Projet ERC : PhysCoMeT (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499381.0 €

There is growing evidence that mechanical forces emanating from the tissue microenvironment can activate biochemical signalling to control gene expression, in a process known as mechanotransduction, for tissue regeneration and organ development. Importantly disruption of this effect by changes in the microenvironment leads to pathological responses including tissue fibrosis and cancer.  The advent of new force measurement techniques and high-resolution microscopy have made it possible to isolate impacts of mechanics from genetic and chemical factors, giving unprecedented access to investigate fundamental questions on how mechanical cues at the tissue scale affect signalling at a single cell level.  The proposed research aims to reveal the physics of mechanotransduction in the context of multicellular aggregates, focusing on the impact of mechanical forces from multicellular motion and the mechanical feedback from the activation of biochemical signalling. My central hypotheses are: (i) localisation of mechanical stresses by the cell environment instructs transcriptional activation to direct multicellular behaviour and (ii) the gradients of mechanical forces in a growing multicellular aggregate can act as guidance cues for the morphology of growing tissue.  I combine experiments on breast cancer cells of varying degrees of aggressiveness, with multiscale modelling - discrete and continuum simulations - to explain the interconnection of transcriptional activation and multicellular motion. This will fill the gap between biochemistry at the cell level and mechanics at the tissue level and is essential to the understanding of physical mechanisms that lead to healthy behaviour or malfunctioning of tissue, as well as to finding proper therapies for diseases that emerge at tissue scales. Moreover, in a field dominated by genetic and chemical understandings, the outcomes of this project will provide a fresh view based on the biophysics of force transmission across the tissue.

Mots-clés : mechanotransduction multicellular motion mechanical stress
Projet ERC : ENTRYHIRE (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Université rhénane Frédéric-Guillaume de Bonn — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1094230.0 €

Firms’ hiring of labor market entrants is crucial for individual access to opportunity and the economy’s skill level. However, it involves a complex search and screening process that is prone to frictions. While macroeconomic research has shown that the efficiency of labor market matching depends on recruitment intensity, micro-level evidence on firms’ underlying behavior remains limited, mainly due to a lack of suitable data. Yet, such evidence is essential for understanding and improving labor market matching, particularly given ongoing demographic change and increasing market tightness in many economies.  The objective of ENTRYHIRE is to provide a systematic understanding of (i) firms’ hiring behavior and outcomes in tightening entry-level labor markets, (ii) the nature of underlying frictions and firm heterogeneity, and (iii) the effects of policies aimed at removing hiring frictions. As a ‘laboratory’ for studying the microeconomics of entry-level hiring, I draw on the German apprenticeship market, which features well-defined vacancy and applicant pools, a structured timeline, as well as exogenous tightness and policy variation.  ENTRYHIRE will collect and combine novel data from different sources, including employer-employee records, a matching platform, and the records of a large-scale hiring assistance program. Moreover, it will develop and implement a survey framework to elicit firms’ hiring tradeoffs. Combined with innovative empirical research designs, the collected data will enable a comprehensive view on firms' typically unobserved search and screening processes and their links to realized hiring outcomes.  The project will create systematic knowledge on the interaction between labor market tightness, firms’ hiring behavior, and public policy on entry-level markets. It will provide new empirical ground for economic models of labor market matching and inform policies aimed at promoting an efficient matching of young workers to jobs.

Mots-clés : hiring,entry level labour markets,labour market policy