Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PASTIME (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
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 : 2000000.0 €

Time matters: timescales determine the fate, behavior and functionality of living matter. Especially the interplay between fast and slow molecular processes is omnipresent in biochemistry (protein folding, enzymatic conversions, molecular signaling, etc.). However, in chemistry, models are lacking to properly understand time and its effect on this difficult biological reality.  PASTIME will lay the methodological foundations for a correct understanding of time in chemistry by introducing memory dependent transition interface path sampling to chemical modeling. We will tune the memory that is kept in simulations by creating new path ensemble definitions. The problem will be made computationally solvable by cutting molecules' pathways short. Long timescale effects will be studied through pathway statistics. We will achieve higher decorrelation in the sampling by designing new Monte Carlo moves in path space, such as alchemical moves that change the identity of atoms on the fly, and smart use of memory expansion with a replica exchange move. These new time concepts will be challenged and experimentally validated in a context of drug transport kinetics: drug (un)binding to protein binding sites, and permeation of molecules through cell membranes. The modeling principles will be converted to new algorithms that are computationally feasible today and will be shared in open software.  With PASTIME we will be able to understand slow time effects in molecular interactions. Appropriate memory reduction and tuning will give us the methods to understand time in an endless range of molecular processes, and this work will contribute to drug design, biochemistry, physiology, catalysis, material and polymer science.

Mots-clés : molecular modeling,statistical physics,molecular dynamics simulations,sampling of phase space,monte carlo sampling,binding kinetics,binding and unbinding kinetics of protein ligand,binding sites,drug transport,drug delivery,retention time,timescales,mutations,screening,liposomes,phospholipids,membrane permeability,permeation,lipid flipflop,membrane asymmetry
Projet ERC : KIDFLUENCER (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
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 : 1999830.0 €

KIDFLUENCER will examine the dynamics of the kidfluencer phenomenon to understand its implications for children’s consumer socialization process. Kidfluencers are generation alpha children (born after 2010) that have highly popular profiles (+ 1.000 subscribers) on social media (e.g., Instagram or YouTube) on which they endorse fun and entertaining content, often containing (sponsored) brand endorsements. Past research merely focused on the negative impacts of kidfluencer activities, such as the commercial exploitation of kidfluencers or the deception of kid followers. This project takes an innovative approach by examining whether kidfluencer activities can be considered as pathways for empowerment and growth contributing to children’s consumer socialization process, while considering potential hazards. Using a three-pronged approach (inspired by cultivation theory), the production, content and impact of kidfluencer activities will be examined, giving a voice to kidfluencers, their entourage and followers. Unique compared to cultivation and consumer socialization research is that children will be considered as active co-creators in the research design, co-deciding upon methodological approaches. By challenging consumer socialization theory’s assumptions of a rational consumer and a linear consumer socialization process, I aim to obtain an in-depth understanding of how children’s consumer socialization process is changing in today’s digital age. A multi-method, longitudinal approach will be adopted, combining quantitative (digital traces netnography, experiments and survey) with qualitative methods (ethnography and expert interviews) to tackle the shortcomings of past research. This comprehensive approach will provide a solid knowledge base on how kidfluencers can be conceptualized as a new, hybrid agent of consumer socialization and whether, to what extent, how and for which children this agent affects young children’s consumer socialization process.

Mots-clés : social media influencer marketing kidfluencer consumer socialization process cultivation theory entertainment education theory ethnography netnography experimental research survey research
Projet ERC : TranscriptShape (Horizon Europe, appel 2025, Consolidator grants)
Entité participante : Danish Cancer Society — Pays : Danemark — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1999965.0 €

In the face of environmental stress, autophagy plays a crucial role in stress adaptation through the maintenance of cellular homeostasis. While extensively studied for its ability to degrade proteins, pathogens, and organelles, the potential of autophagy to degrade RNA remains largely unexplored. Recent findings from my team uniquely reveal that specific subsets of RNA are selectively sequestered and degraded by autophagy in a stress-responsive manner. However, the molecular mechanisms driving this process and its biological implications remain unknown. Based on our preliminary results, I hypothesize that autophagy represents a previously unrecognized, highly regulated RNA decay pathway capable of dynamically shaping the transcriptome in response to cellular stress.  Here, I propose a comprehensive approach to investigate autophagy's impact on transcriptome remodeling in response to hypoxia and UV irradiation in cellular models and during melanoma development in mice. To this end, I will integrate state-of-the-art sequencing technologies with subcellular proteomics, high-content screening, advanced biochemistry, and single molecule RNA imaging. In doing so, we will dissect the molecular signals and regulatory factors guiding this previously overlooked RNA decay pathway. Furthermore, we will determine the biological consequences of pathway dysfunction on transcriptome integrity, cellular fitness, and the shaping of cellular identity. Together, this work will provide crucial insights into the mechanisms governing RNA homeostasis during cellular stress. The findings will challenge our current view of autophagy and uncover fundamental new understanding of gene expression regulation in health and disease, with broad implications across the biological sciences.

Mots-clés : selective autophagy,rna biology
Projet ERC : RefLex (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Syracuse — Pays : Etats-Unis — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 51586.0 €

Is International Refugee Law effective? This is the central question of RefLex, a project that will offer the first comprehensive empirical study of the workings and effectiveness of International Refugee Law (IRL), a body of law partly imbricated with International Human Rights Law (IHRL), domesticated and judicialized to an extraordinary degree across the globe. There are many theoretically and empirically rich studies of effectiveness of International Human Rights Law (IHRL), as well as many other fields of International Law (IL) in constructivist International Relations (IR) in particular. The effectiveness of human rights courts and other bodies is also a well-established academic subfield. However, there are no analogous empirical studies of IRL in practice. RefLex will fill this huge puzzling knowledge gap, thereby making a vital contribution both to refugee studies and to scholarship on the theory and practical workings of IL. It will develop a new dataset, the Refugee Protection Index (RPI), in order to enable our (and other) large-n quantitative studies, identify key cases to trace how IRL comes to be effective, or not. It will also contribute to the burgeoning field of legal mobilization (LM) studies, which again, have failed to examine refugee legal mobilisation in comparative or transnational fashion. It will break new ground here also, by studying LM from above and below by studying both UNHCR’s own LM and that of refugees themselves, both acting via transnational organisations and in local settings. The analysis of the RPI will inform the choice of LM casestudies, in order to develop a new account of when LM emerges and when it is effective. The project aims to provide vital insights at a time when the Global Refugee Regime (GRR) is seen to be increasingly adrift from IL, with over challenges to core norms, and practices focusing on informal cooperation, ‘deals’ and political trading, lacking normative specificity and legal force.

Mots-clés : international refugee law effectiveness of international treaties and norms impact of human rights courts and un treaty bodies legal mobilization role of unhcr refugee legal mobilization
Projet ERC : SCRiBe (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : University College Dublin — Pays : Irlande — Rôle : PI
Acronyme de l'entité : UCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

This project aims to understand the conceptualisation of ‘open’ in the open access movement and the development of open research infrastructure from a transnational perspective by identifying boundaries and constraints that hinder the growth of bibliodiversity in three different geographical regions. Its objectives are to shed light on an overlooked research area in knowledge production: the relationship between standards, geopolitics and transnational knowledge flows by examining the antithesis of openness: boundaries, censorship, and regulations that enforce closures and blockades. WP1 explores and develops the conceptual and methodological dimensions in understanding openness and related concepts, as well as methodological approaches regarding knowledge flows and information boundaries. WP2 examines the inception and development of open research infrastructure, SciELO and African Journal Online (AJOL), both of which have distinct characteristics and follow different timelines and trajectories. WP3 investigates the current development of open research infrastructure in Europe, with a specific focus on standards and standardisation and their potential implications on regionalism, internationalism and globalisation. Following the practices of laboratory studies, the study will gain in-depth understanding by rich description and co-construction of meanings in the research process. In sum, the project will provide novel theoretical and methodological perspectives and unique empirical findings that understand the global inequities of knowledge production with an ultimate goal of fostering sustainable, collaborative, equitable, and bibliodiverse research ecosystems.

Mots-clés : bibliodiversity epistemic diversity open access open research scholarly communication standards and standardization modernization globalization
Projet ERC : RefLex (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University College Dublin — Pays : Irlande — Rôle : PI
Acronyme de l'entité : UCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1910862.0 €

Is International Refugee Law effective? This is the central question of RefLex, a project that will offer the first comprehensive empirical study of the workings and effectiveness of International Refugee Law (IRL), a body of law partly imbricated with International Human Rights Law (IHRL), domesticated and judicialized to an extraordinary degree across the globe. There are many theoretically and empirically rich studies of effectiveness of International Human Rights Law (IHRL), as well as many other fields of International Law (IL) in constructivist International Relations (IR) in particular. The effectiveness of human rights courts and other bodies is also a well-established academic subfield. However, there are no analogous empirical studies of IRL in practice. RefLex will fill this huge puzzling knowledge gap, thereby making a vital contribution both to refugee studies and to scholarship on the theory and practical workings of IL. It will develop a new dataset, the Refugee Protection Index (RPI), in order to enable our (and other) large-n quantitative studies, identify key cases to trace how IRL comes to be effective, or not. It will also contribute to the burgeoning field of legal mobilization (LM) studies, which again, have failed to examine refugee legal mobilisation in comparative or transnational fashion. It will break new ground here also, by studying LM from above and below by studying both UNHCR’s own LM and that of refugees themselves, both acting via transnational organisations and in local settings. The analysis of the RPI will inform the choice of LM casestudies, in order to develop a new account of when LM emerges and when it is effective. The project aims to provide vital insights at a time when the Global Refugee Regime (GRR) is seen to be increasingly adrift from IL, with over challenges to core norms, and practices focusing on informal cooperation, ‘deals’ and political trading, lacking normative specificity and legal force.

Mots-clés : international refugee law effectiveness of international treaties and norms impact of human rights courts and un treaty bodies legal mobilization role of unhcr refugee legal mobilization
Projet ERC : ActSwiftly (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Institute of Molecular Genetics — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : ÚMG AV ČR
Type d'entité : Recherche
Financement ERC de l'entité : 2625000.0 €

Antigen-stimulated naïve CD8+ T cells proliferate and differentiate into effector and memory cells. Whereas effector T cells remove infected or cancerous cells, memory T cells protect the organism from re-infections. Despite decades of research, the challenging central questions of how naïve T cells form diverse progeny and what drives the differential response of naïve and memory T cells to infection remain unanswered, largely because of lacking experimental tools. The goal of this project is to generate a comprehensive model of cell-fate choices of naïve and memory CD8+ T cells in vivo. We will achieve this by addressing three complementary specific objectives:  1) To understand the early and late fate choices in naïve T cells.  2) To uncover differences between naïve and memory T-cell responses and fates.  3) To identify the role of proximal protein kinases LCK and FYN in T-cell fate choices.  We will pursue these aims using a combination of experimental immunology and systems biology. We used the synergy between novel genetic models and single cell atlases (i) to characterize an unprecedented transient stage of activated T cells, (ii) to determine the early gene expression signatures and fate choices of in vivo activated naïve and memory T cells, and (iii) to observe that LCK secures memory T-cell formation. These tools and findings offer us novel perspectives to tackle the challenging objective in its full complexity. We will develop additional unique experimental models coupled with innovative in-silico techniques to uncover the cellular and molecular mechanisms underlying diverse fate choices of particular T-cell subsets and to narrow the gap between mouse and human immunology. Overall, this project has the ambition to resolve long-standing fundamental questions in immunology to open new avenues for targeting and modulating T-cell fates in vivo for efficient vaccine design and for promoting beneficial cytotoxic responses to chronic infections and cancer.

Mots-clés : t cells,fate choices,cytotoxic t cells,lck,signaling,differentiation,mouse models,experimental immunology,omics
Projet ERC : TerpenCode (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Institute of Organic Chemistry and Biochemistry — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : ÚOCHB AV ČR
Type d'entité : Recherche
Financement ERC de l'entité : 2158732.5 €

Enzymes are biological catalysts indispensable for biotechnology. Conventional approaches to enzyme design and optimization, relying on biochemical intuition and combinatorial mutagenesis, have yielded significant success over decades. Building on these foundations, the TerpenCode project aims to instantly elucidate and engineer enzymatic reactions by designing a new generation of deep learning models that (1) incorporate biochemical principles as inductive biases and (2) model all intermediate biochemical transformations that occur sequentially in the active site of each enzyme. We will focus on terpene synthases, which produce the core hydrocarbon scaffolds of terpenoids, the largest and most diverse class of natural products. My group has already curated a comprehensive training dataset comprising thousands of terpene synthase reaction mechanisms. In Objective O1, we will develop deep learning models for predicting the substrates, products, and reaction mechanisms of terpene synthases directly from their amino acid sequences. In Objective O2, we propose to engineer a generative machine learning algorithm for designing new variants of terpene synthases with altered quantitative product distribution, adjusted product stereochemistry, or new reaction cascades that lead to novel terpene products. We will experimentally validate these models by yeast expression experiments, including complete chemical structure elucidation of the detected reaction products. Breakthrough progress on these objectives would be a key important step towards the holy grail of biotechnology: providing a computational prediction of the exact enzyme function from its amino acid sequence and instant de novo generation of new enzymes for catalyzing desired biochemical reactions for an important class of enzymes. Generalizing our solutions further to other classes of enzymes would enable sustainable biotechnological production of a broad spectrum of new-to-nature chemicals and bioactives.

Mots-clés : terpene synthase,biosynthesis,enzyme function,enzyme design,machine learning,deep neural network,stable diffusion
Projet ERC : Arth-Alleve (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université nationale d'Irlande à Galway — Pays : Irlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998885.0 €

Osteoarthritis (OA) is the most common cause of chronic pain in older persons in Europe and is the leading cause of disability. The disease is a condition affecting the joint cartilage and subchondral bone and is frequently accompanied by pain, stiffness, and long-term disability. Chronic pain is the most prominent symptom in most people with OA, and is the most important determinant of disability in patients with osteoarthritis. Treatment guidelines for OA pain management uniformly recommends a range of pharmacological therapies, including paracetamol, NSAIDs and opioids, together with non-pharmacological therapies. However, such therapies are restricted by considerable side effects and limited efficacy, as well as country-specific restrictions on prescriptions (e.g. on opioid use). Given the risks and side effects associated with current therapies, the long-term outlook for OA patients is bleak. Currently there exists no non-pharm effective therapy for OA pain management. OA patients are left with two options: Manage the debilitating chronic pain using over-the-counter and/or prescription medication, with all of the risk and side effects associated with those therapies; or try to independently cope with the pain and all of the personal, economic and societal challenges that chronic pain presented. Within the ambitious Arth-alleve project, we propose to develop a non-pharma side-effect-free long-term therapy for OA patients, providing new hope to the growing cohort of European citizens affected by this debilitating disease. The Arth-Alleve project will explore the concept of attaching neurotoxin molecules to hydrogel particles, to enable the mechanism of nerve blocking to occur, with the hydrogel acting as a long-term anchor preventing migration of the molecule from the target site. This project will truly transform the treatment of chronic OA pain, and the Quality of Life of the large cohort of European patients suffering from the condition.
Projet ERC : AVATAR (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université nationale d'Irlande à Galway — Pays : Irlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999991.0 €

The increasing availability of whole-genome sequences will ultimately transform medicine into personalised medicine. To realise this potential, we need to understand which of the millions of genetic variants in a person’s genome can alter a phenotype. Genome-wide association studies (GWAS) have associated many genetic variants with thousands of phenotypic traits. Metabolomics has further informed GWAS. However, these methods do generally not consider the biochemical network connecting genetic variants with the metabolic phenotype. Additionally, extrinsic factors, such as diet and the microbiome, also modulate the metabolic phenotype. A computational systems approach is required to untangle this complex interplay. In AVATAR, I shall develop and apply a novel mechanistic computational modelling framework that will significantly expand cutting-edge computational models of whole-body metabolism. The novel in silico models will mechanistically describe the network of genetic variants, genes, proteins, and biochemical reactions, as well as underlying physiological processes that are influenced by microbial and nutrient metabolism. I shall devise a novel algorithm to predict phenotypically relevant genetic variants based on a person’s genome and metabolome. The validated algorithm and the modelling framework shall then be used for two distinct biomedical proof-of-concept studies: the diagnosis and diet-based treatment of inherited metabolic diseases and the metabolic pathway-based stratification of individuals with cognitive impairment. AVATAR will enable novel insights into the genotype-phenotype-environment relationship by enabling systematic mechanism-based analyses of genetic variants, diet, and the microbiome. This ground-breaking, innovative, multidisciplinary project will influence precision medicine by providing a personalisable modelling analysis framework that may ultimately provide a foundation for computer-guided diagnosis and treatment strategies.

Mots-clés : computational modelling human metabolism inherited metabolic diseases cognitive impairment microbiome