Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : EM-POWER (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Radboud University Medical Centre — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : Radboud UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997169.0 €

Mental health problems are associated with variation in the brain and genome. The mechanisms underlying these associations are extremely hard to discern because they are subtly distributed across thousands of genes and not specific to neural processes. Meanwhile, a focus on biology tends to induce feelings of helplessness among those affected by mental health problems, as biology is typically seen as deterministic. I propose that both our mechanistic understanding and the sense of personal agency will leap forward if we consider modifiable, heritable social and lifestyle factors (i.e. "environment") centrally within the causal chain from genes to brain to mental health.  Environmental factors are known to be heritable, yet a bottom-up gene-brain causal model prevails due to its intuitive and practical appeal. Standard methods are limited to pairwise associations between the many relevant genetic, brain and environmental variables. The heritable environment is thus hard to account for, let alone embrace as an opportunity. We developed a new multivariate method that can identify patterns of shared genetic effects across thousands of variables. By combining this method with genetically informed causal models and family designs, we will reveal the overall explanatory power and pervasiveness of environment-mediated genetic influences on brain and mental health. We will further characterise these to identify which environmental factors are potential mediators of genetic influences on brain and mental health, when they emerge, and if and how they are personally modifiable.  The goal of EM-POWER is to lay empirical foundations for a new non-deterministic biological paradigm, that leads to new mechanistic insights of environment-mediated biological mechanisms, within this project and beyond. The future outcome is that people know the potential of personal control over biological factors and can break causal chains from genetic vulnerability to mental health problems.

Mots-clés : gene environment correlation mental health well being transdiagnostic psychiatric genetics behavioural genetics neuroimaging genetics multifactorial genetics neurogenetics biological psychiatry
Projet ERC : SAFE-MRI (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Radboud University Medical Centre — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : Radboud UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2984796.0 €

SAFE-MRI aims to prevent needless mortality from breast cancer by optimizing the use and performance of dedicated breast MRI. First SAFE-MRI aims at detecting breast cancer early in women that are currently deemed too young for population screening (age 45-50). Early diagnosis of breast cancer in these women will lead to a large gain in DALY’s averted. I will initiate a prospective screening study inviting women to a one-time only abbreviated breast MRI at the age of 45. The primary outcome will be the cancer detection rate per 1000 women actually screened. This will validate abbreviated breast MRI as standalone screening technique. Psycho-social and risk information will be collected from all participants. Cost-effectiveness modelling will be included. 5-year follow-up will be performed in all women up to, and including, the first screening round at the age of 50. Second SAFE-MRI aims at improving breast MRI by reducing the need for contrast administration. This is a major downside of breast MRI - for women (iv-canulation and a small risk of allergic reactions) and the environment (pollution of surface water). First, I aim to enhance signal changes using a strongly reduced dose of contrast with advanced deep learning (DL). Further studies are tailored at assessment of unenhanced MRI. Particularly, I will validate novel diffusion weighted imaging (DWI) sequences capable of generating high resolution diagnostic images within short scan times using DL-based reconstruction. Furthermore, I will investigate arterial spin labelling (ASL) based breast imaging strategies that show perfusion without the need for contrast administration. Finally, we will combine unenhanced MRI techniques in a general adversarial network to construct synthetic breast MRI images. Repeated reader studies will be conducted to assess image quality and diagnostic value. SAFE-MRI will thus consolidate my leading role in breast imaging and enable me to design the breast screening of the future.

Mots-clés : breast cancer,screening,abbreviated breast mri,mri reconstruction,unenhanced mri
Projet ERC : ReplaceMi (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Vrije Universiteit Brussel — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Microglia are highly versatile brain resident cells that offer tremendous therapeutic opportunities. They are instrumental for maintaining healthy brain physiology and act as the primary modulators of neuroinflammation and disease. Microglial dysfunction has been convincingly linked to a myriad of neurological disorders, making these cells a prime target for therapeutic intervention. Remarkably, microglia are embryo-derived cells that self-maintain for life, with negligible replacement by the bone marrow. This astonishing self-renewal capacity offers a unique opportunity for cell therapy. The ability to replace dysfunctional microglia with healthy or genetically enhanced counterparts may transform the way we treat brain disease. But how can we replace a cell that is so adept at self-renewal in a tissue that is shielded from the periphery? Currently there are no translatable approaches for the specific replacement of microglia. Furthermore, bone marrow progenitors are unable to adopt the embryonic microglial phenotype. By building on our unpublished observations and developing innovative technologies, I aim to lay the foundation for microglial replacement therapy. We intend to develop an original and translatable strategy for the specific and near-complete replacement of embryonic microglia with adoptively transferred progenitors. Next, by combining iPSC differentiation with genetic barcoding, single-cell analysis and in vivo screening, we aim to identify progenitors that efficiently traffic to the brain and engraft as bona fide microglia. Moreover, we will investigate how we can transform microglia into local protein production factories, as a potential basis to treat neurodegenerative diseases. Finally, we will set up in vivo pooled CRISPR screens to identify the gene networks that can modulate and positively enhance microglial disease responses. ReplaceMi has the potential to result in a new and eagerly awaited breakthrough in treating brain disease.

Mots-clés : microglia,macrophage,cell therapy,ipsc
Projet ERC : MERLIT (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Vrije Universiteit Brussel — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1961451.0 €

MERLIT is the first systematic, diachronic and comparative investigation of meritocratic narratives in literature. Meritocratic thinking manifests itself in powerful narratives across the globe, from the constitutionally embedded “pursuit of happiness” to neoliberal narratives of self-enhancement. MERLIT investigates forms of these narratives, which are embraced for their seemingly empowering and universalist appeal, but also criticised for their enmeshment with structures of domination and privilege. MERLIT explores how meritocratic narratives are written, how they are written into cultures, but also how they are written back to in text forms that have shaped the zeitgeist of particular moments respectively. Although research into meritocratic thinking is a vibrant interdisciplinary field, it is characterised (1) by a lack of investigations into the formal principles underpinning – or challenging – meritocratic articulations, (2) by a narrow focus on (white) Western contexts and (3) by a concentration on recent developments. To counter these gaps, (1) MERLIT explores in six work packages how practices of writing have played, and continue to play, crucial roles in shaping meritocratic articulations but also critiques thereof; (2) MERLIT expands the contextual focus of existing scholarship by engaging with radical writing practices from the Global South and a range of transculturally entangled anglophone contexts; eventually, (3) MERLIT challenges perceptions of meritocratic thinking and its critiques as recent phenomena by engaging with changing forms of articulating value, merit and success from the 17th century to the present. Situated at the intersections of literary history, new formalist theory and cultural translation, MERLIT not only offers a literary history of meritocratic thought, but significantly advances our understanding of the workings of a set of hegemonic forms in and through writing, and of the formative, worldmaking role of literature.

Mots-clés : history of thought literary form cultural narrative meritocracy mentalities
Projet ERC : CODI-MAP (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 2625000.0 €

The CODI-MAP aims to address a fundamental question: How do the cerebral cortex and cerebellum cooperate to generate and regulate movements? Despite their pivotal contribution to motor control, the complex nature of cortico-cerebellar interaction remains a mystery. Our recent work has demonstrated a significant interdependency between the cortical and cerebellar activities, however the precise architecture and computational strategy that cortico-cerebellar circuits employ to generate and maintain task specific information is unknown. Here, I propose to comprehensively address the detailed reciprocal connectivity of the cortico-cerebellar circuits, their functional interaction during goal directed voluntary movements, as well as their contribution to sensorimotor learning. Our central hypothesis is that the cortico-cerebellar circuits form complex networks characterized by both extensive convergence and divergence. This configuration provides a spectrum of task-related functional modules for sensorimotor control and learning. By engaging specific functional modules, the cortico-cerebellar networks achieve the required spatiotemporal precision for directing movements. We will first systematically dissect the anatomical and molecular features of the cortico-cerebellar pathways using a suite of sophisticated combinatorial viral-genetic strategies. Next, we will identify and manipulate the functional circuits that control forelimb movements using novel multi-regional electrophysiological and optical methods. Finally, we will combine in silico simulation with dual-regional optical recording and manipulation to uncover the plastic changes within cortico-cerebellar circuits during learning. The outcome of this project has the potential to challenge the conventional perspective that considers cortex and cerebellum as distinct computational entities, proposing a multi-regional integrative circuitry, thereby unveiling fundamental principles of how the brain generates action.

Mots-clés : cortico cerebellar circuits,sensorimotor control,multi regional interaction
Projet ERC : CINbyFUNseq (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
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 : 2000000.0 €

Chromosomal instability (CIN) is a main cause of tumor heterogeneity, tumor evolution and therapy resistance of cancers. Chromosomally instable gastric cancer (CIN-gastric cancer) accounts for 50-70% of gastric tumors and is the poorest prognosis tumor subtype with the most suppressed tumor immune microenvironment. However, it is not understood how CIN contributes to poor prognosis and edits the tumor immune response of CIN-gastric cancer, due to a lack of assays investigating native CIN-driving mechanisms at the single cell level.  I invented a pioneering, microscopy-based functional single cell sequencing method, which enables selective profiling of rare subpopulations of cells displaying dynamic phenotypes of interest. In this proposal, I will use my expertise to develop novel advanced single cell and multiplexed sequencing methods and create a new research line with the aim of dissecting the driving mechanisms of CIN in CIN-gastric cancer, investigating the impact of CIN on tumor microenvironment, and elucidating the molecular pathways leading to the poor prognosis of CIN-gastric cancer. To fulfill this aim, I defined three research objectives:  In Objective I, I will develop a deep learning-based functional single cell sequencing (deepFUNseq) method to identify and profile rare, naturally occurring CIN-mother and -daughter cells derived from CIN-gastric cancer patients. In Objective II, I will develop a multiplexed functional & spatial single cell sequencing method(multi-FUNseq) to transcriptomically profile (non-)CIN gastric cancer cells and their interacting immune cells.  In Objective III, I will investigate CIN-driving mechanisms and CIN-associated consequences in CIN-gastric cancer, including the role of CIN in immunoediting.  The technologies developed in this proposal will result in a leap in our understanding of CIN in the context of cancer, and will lead to advances in fields where profiling cell-cell interactions is important, like tumor immunology.

Mots-clés : single cell technology,single cell sequencing,multi omics profiling,spatial transcriptomics,multiplexed sequencing
Projet ERC : SoBaSyC (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Institut national de recherche en sciences et technologies du numérique — Pays : France — Rôle : PI
Acronyme de l'entité : Inria
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Symmetric cryptography, essential for enabling secure communications, has benefited from an explosion of new results in the last two decades, in big part due to several standardization efforts: many public competitions have been launched since 1997, where the community proposes cryptographic constructions and simultaneously evaluates their security and performance. The security of symmetric cryptography is based on cryptanalysis: we only gain confidence in a symmetric cryptographic function through extensive and continuous scrutiny. However, the current context has not allowed the community to digest all the new findings, as can be seen from several recurrent issues. The two main ones are: 1) primitives proposed at top-tier venues often get broken by slight modifications of already known techniques; 2) published cryptanalysis at top conferences sometimes include mistakes or are suboptimal. They are also often re-invented and re-named.  The main challenge of SoBaSyC is to establish solid bases for symmetric cryptography. Using cryptanalysis as the starting point, my aim is to unify the knowledge obtained through the years on the different families of attacks, to transform it with an algorithmic approach and to endow it with optimizations. The final result will be a toolbox congregating all our newly proposed optimized algorithms, that will provide the best known attacks on a given construction, through an easy application. Next, I plan to derive from this algorithmic approach some theoretical bounds, as well as some properties that I will include in the security proofs of symmetric constructions, providing more meaningful and realistic security arguments.  This would allow, for the first time, to ensure that any newly proposed primitive or construction is already resistant to all known attacks, and will considerably increase the confidence on these functions. It will also save a considerable amount of time and allow the field to advance, at last, on solid ground.

Mots-clés : symmetric cryptography,cryptanalysis,algorithms,attacks,automation,bounds,
Projet ERC : PDC-MAIN (Horizon Europe, appel 2024, Consolidator 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 : 1999610.0 €

The worldwide rise in obesity rates is causing significant harm to human health. While effective weight loss therapies are emerging, the challenge of maintaining weight loss remains unresolved. With this project, we will leverage expertise in drug development to engineer novel peptide-drug conjugates designed to obstruct homeostatic weight regain in a cell specific fashion. In the food deprived state, a subset of hunger promoting neurons undergo structural changes that increases excitability and thus drives homeostatic weight regain. Capitalizing on our knowledge of G protein-coupled receptors (GPCRs) expressed in hypothalamic cell populations we will develop GPCR-targeting peptide-drug conjugates specifically designed to obstruct weight recidivism. To evaluate this drug-targeting approach, neurobiological methods including fiber photometry will be employed to confirm target engagement. Preclinical models are used to investigate the translational potential for treatment of weight loss maintenance following dietary and pharmacological weight loss interventions. The molecular mechanisms of action and receptor-target selectivity of the conjugates will be determined using loss-of-function mouse models. Pharmacokinetic properties of lead candidates will be optimized by incorporating chemical half-life extenders. This bridging between medicinal chemistry, neuroscience and pharmacology will give rise to new multimodal molecules targeting homeostatic weight regain mechanisms to address a vastly growing unmet medical need for weight loss maintenance pharmacotherapies.

Mots-clés : obesity,weight loss,pharmacology,weight loss maintenance,body weight,appetite,hunger,satiety,hypothalamus,agrp,peptide drug conjugates,drug design,medicinal chemistry,peptide chemistry,ghrelin,pyy,leap2,nmda receptor,g protein coupled receptors
Projet ERC : ENERGISED (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut national de recherche pour l'agriculture, l'alimentation et l'environnement — Pays : France — Rôle : Partner
Acronyme de l'entité : Inrae
Type d'entité : Recherche
Financement ERC de l'entité : 314250.0 €

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are immune-related disorders characterized by inappropriate gut inflammation. Their incidence has increased dramatically in Western countries in recent decades, supporting a role for environmental factors. Despite the development of new treatments, IBD are insufficiently controlled in a large proportion of patients, inducing an alteration in quality of life and a socioeconomic burden. A better understanding of the pathogenesis and identification of new therapeutic targets are therefore urgently needed. In this context, the gut microbiota has been recognized as a strong actor in IBD. Additionally, an alteration in intestinal and immune cell energy metabolism has been suggested in the pathogenesis. Classical host-microbe interaction concepts rely on the recognition of conserved microbial motifs by innate immunity sensors or on the action of microbial molecules on a host cell receptor. However, energy metabolism plays a crucial role in mounting the appropriate cellular response, and emerging data indicate that the gut microbiota may directly affect it. I hypothesize that the altered gut microbiota in IBD contributes to the impairment of host cell energy metabolism and pathogenesis. The aims of ENERGISED are to (i) identify the microorganisms and microbiota-derived metabolites impacting host cell energy metabolism and the mechanisms involved and (ii) decipher the consequences of gut microbiota alterations on host cell energy metabolism in IBD and design new microbiota-based therapeutic strategies to manipulate the host cell energy state in IBD.  This challenging project involves multidisciplinary aspects from microbiology to immunology, metabolism, and medicine; the use of multiple cutting-edge technologies; and translational analysis from mice to humans. In addition to its scientific importance, it will have societal impacts due to the identification of new therapeutic strategies.

Mots-clés : microbiome,cellular energy metabolism,inflammatory bowel disease
Projet ERC : AUTO-SELECT (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Telethon Foundation — Pays : Italie — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 1312250.0 €

(Macro)autophagy is an evolutionarily conserved catabolic process induced to preserve cellular homeostasis under conditions of stress, such as nutrient starvation. Upon autophagy activation cellular components are engulfed by autophagic vesicles, which then fuse with lysosomes for substrate degradation. Despite the unquestionable physiological and medical relevance of nutrient- and pharmacological-induction of autophagy in human health, the precise identity of autophagy substrates and the rules governing their selection in vivo are largely unknown. AUTO-SELECT’s goal is to provide a framework to identify physiologically relevant autophagy substrates in different organs and to determine the signaling events that govern their selection. This proposal relies on (1) newly generated mouse models to genetically manipulate autophagy and key autophagy regulators, (2) tools to quantitatively measure autophagy substrate delivery to lysosomes and subsequent degradation in vivo, and (3) -omic technologies and bioinformatic tools to dissect the molecular events that govern substrate selection in response to diverse stimulations in a tissue-specific manner. In addition, AUTO-SELECT will develop new strategies to modulate selective autophagy and test their therapeutic relevance in connective tissue disorders characterized by the intracellular accumulation of misfolded procollagen molecules. AUTO-SELECT has the potential to discover new rules governing cargo selectivity during autophagy and, hence, to provide new links between energy metabolism and cellular quality control that might be exploited for autophagy modulation to treat human diseases.

Mots-clés : autophagy,selective autophagy,lysosome,nutrient sensing,mtor