Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PTMtalk (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
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 : 1489798.0 €

Post-translational modifications (PTMs) regulate all aspects of protein functionality. Dysregulation of PTMs or the enzymes that regulate them is frequently associated with disease. Far from working in isolation, PTMs crosstalk with each other creating decision-making circuits that regulate the cellular adaptation to fluctuating environments. PTM crosstalk is a regulatory layer of the proteome across the tree of life. However, to what extent and how PTM crosstalk regulates biological processes is a long-standing question in biology that is experimentally challenging to tackle. The challenges lie in the natural complexity and infinite combinatorial possibilities of PTMs, and the lack of unbiased systematic methods to study their function. We will use a combination of state-of-the-art CRISPR-based editing methods to construct 30.000 PTM-mutants in all the proteins involved in the signalling-to-chromatin pathways, and a scalable systems biology approach based on reverse genetics and chemical genomics to profile these mutants under 150 stress conditions. Mutants with similar phenotypic profiles are functionally associated, allowing us to infer functional relationships for PTMs, regulators and conditions. These functional associations will provide conditional regulatory PTM crosstalk events at an unprecedented scale. We will further mechanistically dissect the function of selected PTM crosstalk events by interrogating protein activity, cellular localization and interactions. Moreover, we will dissect their directionality and modularity. We expect these findings to be transferable to other eukaryotes due to the high degree of conservation in these core biological processes. Overall, this project will revolutionise the PTM field providing ground-breaking insights into the functional understanding of PTM crosstalk and their regulation in S. cerevisiae and unlocking the door for cracking the PTM code within and across biological processes.

Mots-clés : ptm crosstalk,yeast,phenotypic screens
Projet ERC : THIRSTEE (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
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 : 1478665.0 €

THIRSTEE is a ground-breaking project focusing on sub-Neptunes, a class of planets with masses and radii between those of Earth and Neptune. These planets are the most common in the Galaxy, especially around Sun-like stars, but the most basic questions about their origin and nature remain unanswered. Are sub-Neptunes "gas dwarfs" (Earth-like cores surrounded by large hydrogen-rich envelopes formed near their observed close-in locations) or "water worlds" (planets formed beyond the snow line composed of a 1:1 mixture of ice and rock)? If the latter exist, what are their demographic and individual properties and how do they depend on stellar host type? Do any of them harbour liquid water oceans below their atmospheres?  The gas dwarf hypothesis has the most traction in the field, but recent evidence suggests the existence of water worlds. The observations, however, can be explained by both scenarios due to the modelling degeneracies that surround these planets. THIRSTEE aims to solve this debate using a multi-technique approach combining transit, radial velocity and atmospheric characterization data with a novel statistical framework that accounts for observational biases. This dataset constitutes a valuable addition to the community, enlarging the known sample into unexplored regions of the parameter space and enabling a direct comparison with synthetic planet populations. THIRSTEE is designed to mitigate all the shortcomings that have prevented previous studies from reaching conclusive results about this enigmatic population. For the first time, such an ambitious program can be pursued thanks to the simultaneous operation of state-of-the-art observational facilities. The project seeks to answer key questions about sub-Neptune formation and evolution, their atmospheres, and their demographic properties. Thanks to its unique approach, THIRSTEE will revolutionize our understanding of sub-Neptunes and their potential significance in the search for life beyond Earth.
Projet ERC : ORGANTRADE (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
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 : 1499955.0 €

The organ trade is a relatively new but neglected crime that is proliferating globally. The trade is prohibited universally, yet, the growing gap between organ supply and demand has led to an ‘illegal’ organ market that converges with altruistic organ procurement systems. In this market, growing numbers of desperate patients from the global north travel to the global south to buy organs, often returning with severe medical complications. Similarly, the growing global economic divide and the rise in conflicts and natural disasters are subjecting increasing numbers of vulnerable organ sellers to physical, psychological and financial exploitation on the organ market. Preliminary scholarly work increasingly suggests that this trade is embedded within medical/legal institutions. There is however a critical lack of research and knowledge on how the medical sector, such as hospitals and clinics, and other legal businesses facilitate, conceal and launder illegal transplants. This proposed research aims to understand how, where and why medical/legal businesses facilitate, conceal and launder illegal transplants and assesses the implications for anti-organ trade responses. This project addresses these knowledge gaps through an innovative research program that combines online research, fieldwork and research of the most recently prosecuted cases across the global north and south. It is guided by a unique conceptual framework that combines notions from criminology, transplant medicine and medical ethics. By doing so, this project generates a potentially ground-breaking line of research that radically departs from popular portrayals of the trade as an ‘external’ organized crime and that advances our understanding of the trade as a socio-medical problem that is nested within medical/legal institutions. Insights will be crucial for scientists, policymakers, transplant societies and law enforcement to develop inventive solutions to prevent and disrupt illegal organ transplants.

Mots-clés : organ trade,transplant bio medicine,medical ethics,white collar crime,organized crime
Projet ERC : RADIOBIO (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
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 : 1750000.0 €

Background and unmet need Targeted radionuclide therapies (TRTs) are a promising modality to treat patients with metastasized cancer. TRTs function via systemic administration of radiolabelled molecules (α- and β-particle emitters) designed to target tumour cells. However, the radiobiological effects of TRTs are poorly understood, and rational design of new modalities based on underlying cellular mechanisms is therefore not possible, resulting in suboptimal treatment strategies. Since most patients with advanced cancer cannot be cured at the moment, it is therefore my ultimate goal to improve TRT.  Aim My ERC project aims to identify and quantitate specific radiobiological mechanisms of TRT-radiation effects in vitro and in vivo. Objectives This unique multidisciplinary project will yield critical information on subcellular and intra-tumoural radiopharmaceutical uptake kinetics, DNA damage response kinetics and dose response simulations, and will profoundly increase our knowledge on TRT to push the field forward. I will determine cellular dosimetric parameters for α-TRT and β-TRT, determine effects of subcellular and intra-tumoural localizations of TRT on DNA damage induction and survival, image in vivo TRT efficacy and define effects of treatment heterogeneity to ultimately perform realistic dosimetric simulations in 2D and 3D cancer models. Besides using previously developed techniques, we will develop an innovative new imaging setup for high resolution imaging of TRT by intravital confocal microscopy to image real-time cellular processes of anti-cancer therapies in a living organism.  Expected Outcomes Outcome of my project will not only increase our fundamental knowledge on TRT and yield a novel imaging modality, but additionally has high potential to contribute to improved treatment strategies and ultimately patient outcomes.

Mots-clés : targeted radionuclide therapy,radiobiology,intravital fluorescence microscopy,dosimetric simulations
Projet ERC : MultiMENDo (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université Paris Cité — Pays : France — Rôle : PI
Acronyme de l'entité : UP Cité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1058130.5 €

The MensEndoDiag project aims at finding diagnostic biomarkers and prognostic biomarker candidates, as well as investigating new therapeutic approaches for endometriosis using menstrual fluid, an easily accessible yet overlooked biological fluid. Endometriosis is a common gynecological disorder affecting 6-10% of women of childbearing age. It is associated with pelvic pain and infertility. It leads to a reduced quality of life and is an economic burden. It is defined by the presence of endometrial tissue outside the uterus. Endometriotic lesion form from retrograde menstruation (menstrual fluid reflux through the fallopian tubes) but the precise pathogenesis remains unclear. There are no noninvasive biomarkers currently used in clinical care but they are essential to improve the diagnosis delay, currently estimated at 8 years. There is no specific treatment and pharmacological options are contraceptive. Here, I propose to use menstrual fluid as a relevant biological fluid for endometriosis. In Aim 1, single-cell transcriptomics and soluble protein multiplex assays on 64 menstrual fluid samples will be used to identify candidate diagnostic biomarkers that differentiate endometriosis affected women from healthy controls. Validation of these biomarkers will be carried out in menstrual fluid samples from 250 women. In Aim 2, menstrual fluid derived organoids cultured with or without immune cells will be used to assess endometriosis associated functional changes and to test new immunomodulatory treatments. In Aim 3, longitudinal cohorts will be established to identify prognostic candidate biomarkers for response to surgery and in vitro fertilization. Diagnostic and prognostic biomarkers are essential to assess disease establishment, evolution and to choose the most appropriate treatment. This project will enhance our understanding of endometriosis pathophysiology as well as allow the study of a new biological fluid, relevant to gynecologic and reproductive disorders.

Mots-clés : endometriosis,gynecology,fertility
Projet ERC : SEDAHEAD (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
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 : 1498846.0 €

In a Global Changing world sediment regime has emerged as a dominant actor in the modification of river catchments. The sediment regime refers to the sediment budget (amount, type and timing of sediment inputs, outputs and storage) of a river system as well as the way water and sediment interact to drive river conditions. Studies of sediment regime assessing the impact of Global Change are scarce and traditionally relies on deterministic approaches. However, at any given river catchment section, a complex imprint in the spatial-temporal distribution of sediment regime is observed. This imprint is caused by the temporal and spatial uneven production, storage activation and transport of sediments. Pure deterministic (and thus partial) solutions are not accounting for the natural variability of sediment regime and the inherent uncertainty due to Global Change. This means we are potentially missing half the story and that our attempts to forecast the current and future evolution of rivers areas, at both catchment- and reach-scale, may be more wrong than right. The tenet of this proposal is to describe and determine the Global Change impacts on sediment fluxes at all scales relevant for river catchment management by means of a modelling approach that can account for natural stochasticity and Global Change uncertainty. Three main and novel research questions have been identified and need to be addressed: (i) how (and how strongly) the headwaters control the main features of sediment regime; (ii) how to model sediment fluxes by means of a forecasting model capable to reproduce fluctuating (and thus realistic) sediment regime characteristics; and (iii) how to identify and incorporate the Global Change impacts on sediment regime modelling to assist in fostering a more robust river catchment management. This proposal contributes to the 13th UN Global Goal “Climate Change” and to the Horizon Europe mission: “Adaptation to Climate Change including Societal Transformation”.

Mots-clés : sediment regime river morphology modelling river catchment global change environmental risk assessment
Projet ERC : BiFOLDOME (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
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 : 1496823.0 €

Self-assembly is a fundamental foundation of life, but what about co-assembly? The main goal of BiFOLDOME is to decipher co-assembly to understand self-assembly. Amyloids were assumed to be assembled by one type of protein, but our recent elucidation of the first 1:1 hetero-amyloid structure (the RIPK1-RIPK3 necrosome core) suggests that amyloids composed of two distinct proteins playing key roles in health and disease may be common. In fact, a viral protein (M45) can displace one partner (RIPK1) to form a distinct 1:1 hetero-amyloid (M45-RIPK3). Taking a leaf from the viral playbook, this means that for a given self-assembling sequence there may be a mating sequence driving the preferential 1:1 co-assembly of the two. Thus, understanding what drives the preferential formation of co-assembled forms over conventional self-assembled species will afford an entirely new vision on assembly processes transversal to all fields of knowledge. BiFOLDOME is organized around three different levels of complexity: (1) characterizing the formation, structure and energetics of representative paradigms of 1:1 co-assembled amyloids using solution and solid-state NMR spectroscopies, and energy calculations, featuring novel technical innovations that we will develop. This will provide the basis for self-assembly by delivering a firm understanding of co-assembly. (2) Applying the fundamental knowledge from (1) to the manipulation of self-assembled, disease-associated proteins using the powerful concept of 1:1 co-assembly. (3) Going beyond the state of the art by developing a new methodology to study the assembly of biomolecular condensates. The approach, which I call “optoNMR”, will enable controlled, light-triggered self- and co-assembly of proteins within the NMR tube, opening new avenues to discern between alternative hypotheses for condensate formation and hardening in real-time and at high resolution, or for sensitive detection using hyperpolarization schemes.

Mots-clés : supramolecular assembly nmr structural biology light nmr biological chemistry ripk1 ripk3 tdp 43 1 1 hetero amyloid condensates self assembly co assembly amyloids rhim computational chemistry
Projet ERC : MindTheGap (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Netherlands eScience Center — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : NLeSC
Type d'entité : Recherche
Financement ERC de l'entité : 351250.0 €

Darwin identified the incompleteness of the geological record as a major concern in our ability to reconstruct the evolutionary history from fossils. Geological strata are not, however, a random selection of the past, but are deposited and preserved in processes which can be modelled mathematically. This project employs numerical forward modelling, a technique from sedimentary basin analysis, to quantify how stratigraphic gaps affect evolutionary patterns in the fossil record. It focuses on tropical carbonate platforms, because they are the richest archive of biodiversity through the Phanerozoic and are directly formed by organisms, thus preserving a positive feedback loop between the environment, evolution, and sediment formation. Completeness of the record depends on the time scale of measurement. Previous work demonstrated that long gaps in the record, in the range of 106-107 years, are reflected in biodiversity reconstructions. Here we address shorter gaps (103-105 years), which are more frequent, but harder to detect. They can be predicted using models of stochastic sedimentation, astronomical forcing, and sedimentary and diagenetic self-organization. Forward modelling will be used to simulate the effect of gaps in the record produced by each of these processes on diversity and character evolution. This will allow us to answer the questions: What part of diversity do we miss owing to the missing rock record? Are the preserved intervals exceptional or representative? Is there a systematic part of biodiversity and environmental records which will always fall into gaps? By applying the findings of the forward modelling to fossil successions, we will be able to identify and correct for the missing parts of the record and formulate testable hypotheses on the original tempo and mode of evolution at the highest temporal resolution achievable in the geological record.

Mots-clés : stratigraphic palaeobiology,self organization,trait evolution,character evolution,phylogenetics,basin analysis,diagenesis,carbonate sedimentology,age models,stratophenetics,brownian motion,orbital forcing,astrochronology
Projet ERC : SPLIFEM (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Centre européen de recherche en biologie et en médecine — Pays : France — Rôle : Partner
Acronyme de l'entité : CERBM
Type d'entité : Recherche
Financement ERC de l'entité : 474158.0 €

In eukaryotes, the spliceosome removes non-coding introns from precursor messenger RNAs during pre-mRNA splicing. Crucially, many pre-mRNAs are spliced differently depending on cellular status or external stimuli. This “alternative splicing” reshapes the genetic information from a given mRNA to encode several protein isoforms and greatly diversifies proteomes. Splicing must be extremely precise as errors produce aberrant mRNA encoding potentially toxic proteins. Splicing fidelity relies on the accuracy of the spliceosome that assembles de novo on each pre-mRNA in a cotranscriptional manner, gets activated and selects the precise boundaries of introns to catalyse their excision. The spliceosome is endowed with two apparently conflicting properties: it must be very accurate to avoid splicing errors while being tolerant to accommodate alternative splicing changes. I. aim to unveil the molecular basis of splicing fidelity’s enforcement and modulation by the spliceosome. Due to its extreme complexity, the spliceosome has long been a major challenge for molecular and structural investigations. Recent progresses in cryo-EM allow the structural analysis of very dynamic and low-abundance biological objects such as spliceosomes. Hence, it is now possible to explore the most elusive aspects of RNA splicing, provided that the biochemical challenges of trapping and stabilising transient spliceosome intermediates are overcome beforehand. I will use innovative methods to capture spliceosomes from cell extracts and cryo-EM to investigate how splicing fidelity is: • enforced by molecular checkpoints during spliceosome activation • maintained/modulated by other cellular processes • impaired during viral infection The outcome of this research will bring us closer to answering a fundamental question of biology: how does the spliceosome give rise to the immense combinatorial space of alternative splicing without errors and allow the 20,000 human genes to yield 200,000 proteins.

Mots-clés : spliceosome cryo em splicing fidelity ribonucleoprotein remodelling
Projet ERC : HorizonGT (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Madrid Health Service — Pays : Espagne — Rôle : PI
Acronyme de l'entité : SERMAS
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 1497613.0 €

Horizontal gene transfer (HGT) –the movement of genetic material between individuals– is a significant force fueling bacterial evolution. Through HGT, bacteria acquire new traits, develop new metabolic capabilities and learn to withstand harsh environmental conditions. However, in some cases, HGT brings genetic information that is not advantageous to its host. Despite its crucial relevance for bacterial ecology and evolution, understanding the selective forces that drive the success (or failure) of HGT remains a major challenge. Previous studies addressing this challenge ignored the fact that not all HGT events are alike: incoming DNA can be integrated into the host genome (e.g., transposons, integrons), or it can stand as a physically separated, autonomous DNA molecule (e.g., plasmids). This difference in genomic context poses several mechanistic constraints that are likely to alter the evolutionary outcome of HGT.  Here, I will present a conceptually novel approach that explicitly considers genomic context to uncover the selective drivers of HGT in bacterial populations. First, I will develop a new genetic technology to obtain high-throughput fitness measurements of thousands of HGT events. Then, I will use these data to identify and quantify the constraints that determine the success of HGT, both considering the intrinsic effects of the transferred DNA and the role of genomic context on host fitness. Specifically, I will measure the fitness effects of genetic transfers mediated by plasmids (Obj. 1) or integrated into the chromosome and, in the latter case, in different regions of the chromosome (Obj. 2). Finally, I will leverage the rules derived from these analyses to reconstruct the role of HGT in the evolution of a relevant human pathogen (Obj. 3). This project will provide a quantitative and mechanistic understanding of the selective forces driving HGT, expanding horizons in evolutionary microbiology.

Mots-clés : horizontal gene transfer,plasmids,fitness costs,chromosomal organization