Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : GOAL (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1473000.0 €

Living materials process information through their physical degrees of freedom, enabling autonomous functions beyond the capabilities of electronic systems. For example, a migrating cell uses its own shape dynamics to navigate through complex environments and decide which way to go. Yet, the principles underlying such physical information processing have not been identified due to the complexity inherent to problems involving fluctuating dynamic boundaries, and the need for a multidisciplinary approach to link theory with experiments.  Building on recent scientific and methodological advances from my group, I propose to investigate how soft active materials perform computations and self-organise functional behaviours using the deformations of their own shape. Specifically, using surface anchoring effects in anisotropic materials as a paradigm for physical shape sensing, GOAL will identify how information is transferred from the covariant dynamics of active boundaries to surface-controlled bulk states, enabled by our novel approach to simulate active surface fluctuations (WP1-2). Combining theoretical results with experimental data from the technological frontier of biology, we will identify how the coupling between anisotropic materials and their geometry generates functional behaviours, such as autonomous object avoidance or embryo self-organisation (WP3). Lastly, we will leverage the visual accessibility of geometrical features to probe how machine learning approaches infer geometry-driven states and transitions from images, and to test our information theoretical predictions on shape sensing (WP4).  GOAL will likely lead to the discovery of universal principles for shape-adaptive matter, because the nonlinear dependencies that arise from geometrical relations express fundamental mathematical properties of space that hold across all scales and contexts.

Mots-clés : physical information processing,anisotropic living matter
Projet ERC : PalmERASERs (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1495519.0 €

Metastasis is the major cause of death in patients with cancer. A better understanding of the mechanisms driving metastasis is critical to develop more effective anti-cancer treatments. The fatty acid palmitate has been recently identified as fuel for metastasis-promoting pathways. However, why palmitate has such a unique pro-metastatic effect compared to other fatty acids with similar metabolic fates remains elusive. Strikingly, I discovered that palmitoylation, a reversible post-translational protein modification driven solely by palmitate, is essential for metastasizing breast-cancer cells. Unexpectedly, I found that palmitoylation ‘erasers’, enzymes that remove the modification, are essential to sustain pro-metastatic effects of palmitate during metastatic colonization. Therefore, I hypothesize that, in palmitate-rich conditions (e.g under high-fat diet), palmitoylation anchor oncogenic proteins to membranes to get activated (functioning as a priming event), while erasers act as a rate-limiting release step, allowing primed proteins to engage in pro-metastatic signaling. I will investigate how the dynamics of palmitoylation promote metastasis by focusing on the erasers, whose role in metastasis remains largely unexplored. Specifically, I will: 1) define how erasers influence pro-metastatic signaling events in metastasizing cells; 2) investigate how erasers activity is regulated in metastasizing cells; and 3) assess how organ microenvironments and palmitate-rich diet condition eraser activity. I will address this by integrating multi-omics, molecular biology and mass spectrometry techniques with clinically relevant in vivo metastasis models. PalmERASERs will serve as a proof of concept for palmitoylation-based therapies with the goal of preventing or treating metastases. By focusing on the influence of diet, I will also enhance clinical translation of these findings by defining which patients will respond most effectively to palmitoylation-based therapies.

Mots-clés : metastasis,post translational modifications,palmitoylation,palmitate metabolism,breast cancer,high fat diet,anti metastatic therapies
Projet ERC : DEGLYCAR-T (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : PI
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1500000.0 €

T cells engineered to express tumour-specific chimeric antigen receptors (CAR) proved effective against B-cell tumours. However, as the technology moves to solid cancers, clinical responses have not been as robust. In this setting, several barriers need to be overcome, including poor tumour recognition and a highly immunosuppressive tumour microenvironment (TME). Altered glycosylation is a hallmark of cancer, often manifesting as incomplete synthesis of O-glycans and increased branching of N-glycans. Glycosylation can mask epitopes to antibodies recognition and suppress anticancer immunity. My Unit was the first to report that N-glycans protect tumours from CAR-T cells and that pharmacological inhibition of N-glycosylation improves efficacy of CAR-T cell therapy in solid malignancies. With the aim of generating a single cell product able to safely offset multiple barriers of tumour resistance, I propose to engineer CAR-T cells to locally express an enzyme able to de-glycosylate tumour and TME cells. This goal will be achieved through the selection of a mutant able to deglycosylate the surface proteome of target cells. To regulate its function in CAR-T cells, I plan to test different systems based on the use of specific promoters, the inclusion of artificial miRNA target sequences, or the generation of a transmembrane variant. A deep characterization of the selected product will be performed in mice reconstituted with a human haemopoietic system. This model will allow to study the efficacy and safety of the proposed approach, and to assess its ability to remodel the TME toward a pro-inflammatory state. I believe that this project will have an immediate impact on cancer immunotherapy, will fuel the development of antiviral approaches and will provide new technological platforms. I have a deep knowledge of CAR-T cell therapy and have established a great network in the field. Despite ambitious, I believe I have the right skills and tools to make this project a reality.

Mots-clés : chimeric antigen receptors,t cells,cancer
Projet ERC : ChOReS (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université Érasme de Rotterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : EUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Background and unmet need: The mammalian genome is a highly organized structure where distinct chromosomal domains occupy discrete territories and position in a non-random fashion. Genome organization also determines the proper functioning of various biological processes, including DNA replication. Genome organization has been widely studied in the context of gene regulation, while recently the role of genome organization in mediating DNA damage repair at DSB sites has also come to light. However, there is scarce information on how newly replicating region is organized in response to replication stress. Hypothesis to be tested: My hypothesis is that stalled replication forks, especially at the regions prone to acquire breaks, undergo compartmentalization/re-organization within the 3-D nuclear space in response to replication stress to allow efficient fork protection and fork restart ability. Objectives: This unique multidisciplinary project will yield critical information to reveal hidden connections of chromatin organization, replication fork stability and chemoresistance. With this ERC project, I will determine for the first time i) the mechanistic insights of chromatin organization changes mediated by chromatin remodeling activity in response to replication stress, ii) identify novel chromatin mobilizers associated with replication forks and iii) determine the significance of chromatin reorganization to cope with replication stress for establishing resistance towards chemotherapeutic drugs in cancer cells and patient samples. Expected Outcomes: My project will not only advance our fundamental knowledge on spatial & temporal reorganization of chromatin architecture containing stressed replication forks, but it also has a high potential to contribute to identifying novel targets aimed at chromatin organizers that mediates resistance towards replication stress inducing chemotherapeutics.

Mots-clés : replication stress,chemotherapy,3 d chromatin organization,replication fork stability
Projet ERC : SeleCStem (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1499948.0 €

Despite huge advances in cancer treatment, resistance to chemotherapy is still common. It is now well established that a small population of cells named cancer stem cells (CSCs) have high tumorigenicity and are able to initiate and maintain a tumour. CSCs usually remain in a quiescent state that is not affected by standard chemotherapy; thus, they are often responsible for treatment resistance and relapse. There is a clear need to find effective treatments against CSCs to fully eradicate the tumour. However, the close similarities of CSCs to healthy stem cells hinders the identification of selective drugs. In the last years, new drug modalities are emerging to provide therapeutic options for challenging targets and diseases, expanding the drug discovery landscape. In line with these trends, SeleCStem aims to develop innovative chemical biology strategies to target CSCs in a safe and effective manner. It will exploit the activity of the enzyme ALDH, which is overexpressed in CSCs of many cancer types, to obtain selective drugs using three orthogonal strategies: we will use the oxidoreductase activity of ALDH to trigger the selective (1) accumulation or (2) release of drugs inside CSCs and (3) use external light to inhibit ALDH only in the tumour area. Successful strategies will be combined at the end of the project to overcome potential limitations of the individual approaches, hence massively increasing the drugs’ selectivity and efficacy. We will design these molecules with the aid of docking studies, synthesise them, and assess their ALDH- or light-triggered activation in purified enzyme assays and in CSC spheres. Overall, we will develop the proof of concept of unprecedented approaches to eliminate CSCs with outstanding precision, thus overcoming some of the limitations of conventional small molecules going beyond state-of-the-art chemical biology. Our ultimate goal is to contribute to improve cancer treatment and increase complete remission rates.

Mots-clés : cancer stem cells photopharmacology drug selectivity aldh
Projet ERC : ARISER (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : Centre de coopération internationale en recherche agronomique pour le développement — Pays : France — Rôle : PI
Acronyme de l'entité : CIRAD
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Crop diversity is a key resource for smallholder farmers in drylands, as it plays a major role in their resilience by stabilizing crop production in the face of climate variability. Although access to crop diversity is pivotal for these farmers, the processes driving access are not fully understood. Previous research indicates that access to crop diversity may rely on the social networks through which crop seeds and information are diffused. These networks display a wide diversity of patterns, including differences in the composition of the actors involved and in the structure of the pathways through which seeds and information diffuse. Understanding the consequences of these different network patterns for crop diversity and their implication for farm resilience is a crucial and timely challenge. In this project, I will address this challenge by combining theory and methods from agroecology and social network research to tackle three objectives: (1) identify the most critical network patterns to maintain high crop diversity on farms over time or to change crops, (2) assess the relation between network patterns and temporal stability of crop production at the farm level, and (3) assess how farmers socioeconomic characteristics affect their access to seed and information. To reach these objectives, I will (i) design a standardized protocol to collect longitudinal and panel data across three dryland areas in Africa, which could serve as a reference for future studies, (ii) build an innovative simulation model combining agent-based and network approaches, and (iii) develop new statistical methods for network analysis. This project will enable a major advance in our understanding of the processes driving farmers access to crop diversity and their resilience. By doing so, it will contribute to improve decision-making for smallholder farmers adaptation to increased climate variability in drylands.

Mots-clés : crop diversity,social networks,adaptation,drylands,small scale farming,complex systems modeling,seed systems,climate variability,africa
Projet ERC : POLIS (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : German Center for Neurodegenerative Diseases — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DZNE
Type d'entité : Recherche
Financement ERC de l'entité : 1499749.0 €

There is growing evidence that currently used toxicological assessments of chemicals fail to fully capture their actual biological activity. While chemicals are routinely tested for acute toxic effects, often at high concentrations, potential function-modulating effects at low concentrations are often underexplored. The inclusion of up-to-date high-resolution methods in the toxicological screening praxis would allow instead to fully capture the complex bioactivity profile of these compounds, which depends on numerous aspects including bioavailability, route of exposure and individual susceptibility. While the last 100 years have seen an enormous number of chemicals introduced into our daily life, of which a large number are well-known to persist in the environment, a sufficient understanding of their bioactivity potential is lacking. Also based on growing evidence, it is not far-fetched to hypothesize that some of these industrial chemicals could be partly responsible for the constant increase of non-communicable diseases including autoimmune diseases, chronic inflammatory diseases but also cancer or (neuro)degenerative diseases. Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) are a class of xenobiotics with proven strong toxicity at high-level exposure, while little is known about their bioactivity at concentrations commonly detected in human samples. Considering their high stability and ubiquitous occurrence in the environment and human body, exposure to PFAS has reached a pandemic scale. I postulate that it is of outmost importance to finally dissect the potential of these compounds to molecularly interfere with organ functionalities at the single-cell level using state-of-the-art high-resolution omics technologies. Supported by an interdisciplinary training in pharmacology, systems immunology, omics, animal and cellular models, and bioinformatics, I represent a prime candidate to successfully develop this project and clarify the bioactivity of PFAS.

Mots-clés : pfas,environmental pollution,chemical bioactivity,forever chemicals,systems immunology,adaptive immunity
Projet ERC : TRANSIT-ND (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : German Center for Neurodegenerative Diseases — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DZNE
Type d'entité : Recherche
Financement ERC de l'entité : 1495557.0 €

Dementia and other neurodegenerative diseases are among the leading causes of disability worldwide and have an immense societal impact due to lack of effective treatments. For developing better preventive and therapeutic strategies, it is essential to clarify their still largely elusive genetic basis and pathophysiology. Emerging insights from the study of rare hereditary repeat expansion disorders caused by elongations of repetitive DNA sequences ("tandem repeats" (TRs)) indicate that TRs could induce instability of neuronal DNA ("neurogenomic somatic instability"), and thereby instigate molecular changes that lead to neuronal degeneration. However, the role of highly prevalent TR variations or their somatic instability in the pathogenesis of common age-associated neurodegenerative diseases is unknown. Here, I aim to assess the role of TRs and their somatic instability in the pathogenesis of neuronal degeneration, the defining hallmark of all neurodegenerative diseases. To this end, I will 1) systematically identify TRs whose size or somatic instability are related to neuronal degeneration in the general population and/or disease severity in repeat expansion disorders, using an innovative approach combining "liquid biopsy" of neuronal tissue, high-throughput ultra-deep long-read DNA sequencing and ultrasensitive biomarkers of neuronal degeneration, 2) delineate the neuroanatomical pathways affected by TR somatic instability through comprehensive neuroimaging analyses, and 3) disentangle the underlying molecular and cellular mechanisms, using an extensive integrative multi-omics approach with experimental validation in neuronal cell lines and post-mortem human brain tissue. The wealth of unique insights from TRANSIT-ND could substantially increase our understanding of the pathogenesis of neuronal degeneration and provide shared targets for the prevention and treatment of a range of different neurodegenerative diseases that afflict millions of people globally.

Mots-clés : neuroepidemiology,genetic epidemiology,neurodegenerative diseases,tandem repeats,repeat expansion disorders,huntington disease,spinocerebellar ataxia,somatic instability,genetic association study
Projet ERC : B-SELECT (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Leiden University Medical Center — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : LUMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499935.0 €

One-fourth of the global population is currently infected with helminths, which modulate host immunity against not only their own antigens but also non-cognate antigens, including vaccines. While antigen-specific antibodies and memory B cells are essential for protection against infectious diseases, how the B cell response quality is influenced by helminths remains largely unknown. With my core expertise in studying responses to parasites at the level of single B cells and monoclonal antibodies, I aim to delineate the onset and quality of B cell responses formed during immunoregulatory helminth infections, impacting the development of effective vaccines. The B cell response quality relies on recruiting antigen-specific naïve cells and selecting high-affinity B cells to form antibody-secreting cells and memory B cells. However, how these well-established mechanisms are impaired during B cell immunity modulated by helminths remains unknown. Therefore, the goal of this ERC proposal is to elucidate the molecular principles governing the formation and selection of antigen-specific B cells during helminth-induced immunoregulation and to identify strategies to mitigate modulation. To achieve this, I will investigate the origin and development of de novo helminth antigen-specific B cell responses in the unique controlled helminth infections in naïve individuals and vaccine-specific B cell responses in residents of helminth-endemic areas. Access to clinical samples, advanced human tonsil organoids and transgenic mouse models, combined with my state-of-the-art expertise in studying antigen-specific B cells, uniquely positions me to uncover paradigm-shifting molecular principles that guide B cell responses during helminth infections. Ultimately, I aim to provide the first proof of concept to mitigate modulatory effects and rescue B cell response quality, paving the way to address global health challenges by inducing protective vaccine response in helminth-infected individuals.

Mots-clés : helminth infections,antibody repertoire,single b cell studies,vaccine responses