Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PHAGE-PRO (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Helmholtz Zentrum München — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : HMGU
Type d'entité : Recherche
Financement ERC de l'entité : 428913.0 €

Amid the antibiotic resistance crisis, the century-old practice of phage therapy, the use of bacterial viruses to treat bacterial infections, has gained renewed attention. Despite extensive research and clear-cut advantages over antibiotics, phage therapy has yet to gain momentum. This is primarily due to remaining limitations, e.g., the time-consuming process of identifying suitable phages and limited in vivo efficacy. With PHAGE-PRO I propose a new technology to overcome the shortcomings of traditional phage therapy. Unlike the conventional use of lytic phages, I will capitalize on prophages – viruses that integrate into bacterial genomes capable of excision and replication. By integrating prophages into safe carrier strains, originating from probiotics, I will unlock two pivotal benefits, (1) rapid identification of suitable phages using advanced machine learning, (2) sustained in-vivo efficacy. Yet, the core advantage of PHAGE-PRO lies in its unparalleled synergy of phage killing and pathogen competitive exclusion imposed by the probiotic. To realize this concept, the development of predictive tools is essential to quickly identify the most promising prophages and probiotic combinations for each pathogen (WP1). Prophage engineering (WP2), followed by rigorous in vitro testing will ensure a high safety and efficacy. High-throughput in vivo experiments using wax moth larvae will reveal the most promising candidate which I will subsequently validate through a proof of principle experiment using a poultry model (WP3). Although I initially tailored PHAGE-PRO to treat Salmonella infections in poultry, its impact extends far beyond: This new technology holds the potential for transformative changes in phage therapy, not only advancing infection management in livestock farming through the enhancement of animal health and the assurance of food product safety, but also by opening the door for targeted preventive and therapeutic interventions in human medicine.

Mots-clés : phage therapy,prophage engineering,probiotics,antibiotic resistance,resistance evolution,bioinformatics,in vitro testing,in vivo experiments
Projet ERC : CONCRETER (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1389028.75 €

The foundations of modern hydrogeology have been built within the paradigm of quasi-equilibrium temperature distribution within groundwater systems. The presumed thermal stability of groundwater is vitally important for many groundwater and stream ecosystems which cannot tolerate a wide temperature range and face growing threats from climate and land-use changes. Yet, recent results evidenced the great impact of ongoing atmospheric warming on shallow groundwater temperatures. Groundwater flow is expected to strongly affect groundwater and stream warming trends. A major issue is that existing modeling frameworks have largely sidestepped (1) the complexities associated with the multi-scale heterogeneity in groundwater flow, and/or (2) the transient nature of groundwater fluxes and surface temperature. Furthermore, direct field evidences of the impact of climate and anthropogenic forcings on the temperature distribution are still rare. The CONCRETER will therefore assess the role of groundwater dynamics in shaping the thermal regime of the critical zone, the shallow subsurface where the water, element, energy and biological cycles interact. The focus on the interaction of subsurface heterogeneity with heat transport processes will require the development of original numerical models (WP1) and novel temperature imaging laboratory experiments (WP2). WP3 will bring critical in situ data to constrain these newly developed models. WP4 will further develop advanced numerical models to separate the effects of fluid flow and of surface warming. With the help of the developed numerical approaches, WP5 will study the evolution of temperature at field sites (characterized in WP3) chosen to isolate the role of different forcings (climatic, anthropogenic) on critical zone thermal regime. CONCRETER will provide new physical frameworks and modelling tools for multi-scale heat transport processes in the critical zone, with the potential to re-define their quantitative understanding.

Mots-clés : heat transport,fractured media,groundwater flow,flow channeling,thermal dynamics,borehole climatology,monitoring,sensing,modelling,geothermal energy
Projet ERC : 3DGenomeSearch (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Institut für Molekulare Biotechnologie — Pays : Autriche — Rôle : PI
Acronyme de l'entité : IMBA
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1500000.0 €

Homology-directed repair is an essential, evolutionary conserved DNA repair pathway that accurately restores genetic information lost due to double-stranded breaks. Its key step is the ‘homology search’, where the broken DNA end locates its matching sequence, typically located on a sister chromatid, to use as a repair template. Despite its significance, the biophysical mechanism of this search within the complex environment of vertebrate genomes remains debated. Emerging hypotheses propose that this search is driven by ‘nucleoprotein’ filaments comprised of repair proteins bound to the broken DNA ends, that actively traverse the nuclear space to find and recognize homologous sequences. We will explore this mechanism by developing quantitative biophysical models that integrate the latest experimental insights on the 3D architecture of sister chromatids and dynamics of nucleoprotein filaments. Our specific aims are: (1) Model the homology search in 3D to understand how broken DNA sites navigate the complex nuclear environment and identify homologous sequences on intricately folded vertebrate sister chromatids. (2) Explore the microscopic mechanisms that drive the large-scale motions and efficient homology search by nucleoprotein filaments. (3) Understand the role of filament-driven homology search in the pairing of homologous chromosomes during meiosis. By integrating these complementary aims, we will build a detailed biophysical, mechanistic picture of homology search. We will calibrate our models against genomic and microscopic datasets, and test their predictions in collaborations with several experimental biology groups. This modeling will provide mechanistic insights into homology search, rigorously test long-standing hypotheses, and generate predictions to guide future experiments. The proposed research will significantly advance our understanding of this key DNA repair process and its potential roles in maintaining genome stability and meiotic recombination.

Mots-clés : chromosome conformation,hi c,biophysical modeling,polymer physics
Projet ERC : KnotSeen (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Madrid Institute for Advanced Studies — Pays : Espagne — Rôle : PI
Acronyme de l'entité : IMDEA
Type d'entité : Recherche
Financement ERC de l'entité : 2498960.0 €

Quantum materials host many exotic and useful phases, and harnessing these states has spurred tremendous research effort. However, the full potential of quantum materials lies in the rich landscape of higher-energy hidden phases, those which are not thermally accessible. Ultrafast laser excitation has recently emerged as a way access these hidden phases, leading to the idea of re-writing material properties “on demand”, but these states usually only survive for hundreds of picoseconds. Thus a key outstanding question remains: how can we stabilize light-induced phases? One key mechanism which can stabilize a phase is topology. The ultrafast phase transitions induced by femtosecond laser pulses naturally lead to the generation of topological defects. These defects, which can only relax after propagating until they encounter another topological defect, could either offer a route to stabilizing light-induced phases or impede their formation, and have been invoked in both contexts to explain many observations. However, actually imaging these nanometer scale defects on the femtosecond to nanosecond timescales required for light-induced phases has not been possible, and so the role of topological defects in light-induced phases remains unclear.  In KnotSeen I will perform the first real space imaging of topological defects in light-induced phases using coherent XUV imaging methods, which provide the necessary spatial, temporal, and spectral resolution to map topological defects at the nanoscale and out of equilibrium. I will map the creation, propagation, and destruction of topological defects in two important cases: quenched superconductivity in the cuprates and light-induced phases in the manganites. A novel data analysis approach will be used to distinguish repeatable from stochastic dynamics at the nanoscale. KnotSeen will reveal the mechanisms by which topological defects control light-induced phases, enabling new tools to stabilize and selectively control them.

Mots-clés : light induced phases,topological defects,ultrafast,coherent imaging,nano imaging,high harmonic generation,xuv,superconductivity
Projet ERC : REWIRE (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : CeMM Research Center for Molecular Medicine — Pays : Autriche — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1499730.0 €

Lymph nodes (LN) are communication centers within the lymphatic network that instruct T cell priming and differentiation in homeostasis and disease. Multiple layers of control are achieved by a complex network of signals from stromal and immune cell compartments. As a result, spatially segregated LN niches coexist that foster diverse T cell lineages. In the context of cancer, T cell differentiation is pushed towards the lineage of exhaustion, with a progenitor exhausted T cell population arising in the LN. Hence, LN are central anatomic sites where T cell exhaustion can be controlled and reversed to eliminate cancer. The key question of REWIRE is: What microenvironmental factors determine the differentiation and maintenance of progenitor exhausted T cells in the LN? Tumor-derived signals reprogram stromal and immune cells within tumor-draining LN. Thus, a premetastatic niche is formed that supports future metastatic seeding while establishing an immunosuppressive microenvironment. I hypothesize that signals guiding T cell differentiation are altered by premetastatic remodeling of the LN niche, resulting in the generation of exhausted T cells. In this project, I aim to (1) decode spatial determinants of the progenitor exhausted T cell niche; and to (2) manipulate the tumor-draining LN ecosystem to control T cell immunity. The overarching goal is to dissect how tissue architecture directs molecular responses within the LN niche to regulate T cell exhaustion. We will use high-dimensional imaging technologies to chart the spatial context of progenitor exhausted T cells following tumor progression; as well as a novel myeloid cell-based in vivo delivery platform to specifically target tumor-draining LN. REWIRE will uncover basic mechanisms of communication between the LN microenvironment and differentiating T cells in the LN; as well as explore the novel concept of controlling T cell responses via manipulating key-features of the LN niche.

Mots-clés : tumor draining lymph nodes premetastatic niche tumor microenvironment
Projet ERC : QUANTAGE (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : CeMM Research Center for Molecular Medicine — Pays : Autriche — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1499046.0 €

Aging is a complex biological process that manifests across diverse anatomical scales, from molecules and cells to organs and organisms. Despite the significance of age-associated diseases in affecting quality of life and mortality, our understanding of how cellular-level changes result in tissue-specific loss of function remains incomplete. Several limitations persist: the inability of animal models to fully mirror human physiology, the restricted scope of longitudinal human studies to easily accessible organs, and a prevalent cell-centric focus that overlooks the broader microanatomical context. Additionally, the challenge of uncoupling aging from pathology is exacerbated by the absence of baselines defining healthy aging, hindering the accurate interpretation of alterations. To address these challenges, the proposed project leverages large-scale human tissue imaging datasets and machine learning techniques. Specifically, Aim 1 employs unsupervised learning to systemically quantify and categorize microanatomical structures across 40 human tissues. In a parallel stream, Aim 2 aims to detect and characterize the manifestation of age-associated pathologies in tissue, pinpointing the molecular changes associated with them, across spatial scales. Aim 3 integrates the insights from previous aims, seeking to identify how they contribute to the process of aging and onset of age-associated diseases. Ultimately, this will unearth early predictors of pathology, providing a transformative approach to disease detection and management. This project will not only offer a novel, comprehensive view of human tissue complexity in the context of aging but also challenge the traditional notion that age-associated pathology is merely an aggregation of cellular dysfunctions. By quantifying the interconnected aspects of tissue architecture changes with age, and the manifestation of pathology, we aim to redefine our understanding of the onset of age-associated diseases.

Mots-clés : organ wide cellular dynamics multi scale tissue architecture tissue specific aging and pathology predictive modeling of disease onset
Projet ERC : FLORA (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1017762.8 €

Food systems are crucial to end hunger, but also to mitigate and adapt to climate change, to protect and restore biodiversity, to ensure human health and well-being, to end poverty, and to support sustainable communities. While hunger has receded, food systems are causing increasingly severe damage to our environment and health. The FLORA project will contribute to a transformation of global agri-food production, trade, and consumption necessary to achieve sustainable and healthy food systems.  The project will create essential evidence to identify and implement the shifts in practices and behaviours needed to effectively achieve this transformation, by (1) making a diagnosis of the integrated health and environmental outcomes of food systems globally, from the production and consumption perspectives, with innovative measures of sustainability, (2) identifying key threats and opportunities with system dynamics and complex network analyses, and (3) targeting and evaluating tailored solutions with an inter-disciplinary modelling framework. The project will enable the identification of most effective, targeted solutions by considering trade-offs, synergies, and dynamics of key food systems components. Global in scope, it sets the ambitious goal to overcome barriers in current approaches by taking a systemic approach and establishing a robust, interdisciplinary framework supported by empirical advancements to tackle complex food systems challenges. This innovative project builds on the PI’s excellent track record in leading interdisciplinary research focused on the global agri-food system and its environmental impacts.

Mots-clés : food systems
Projet ERC : HeliUM (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université libre d'Amsterdam — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2215408.0 €

Laser cooling of atoms has revolutionized physics and allowed studying nature with unprecedented sensitivity, precision and accuracy. With their additional degrees of freedom, ultracold molecules offer even more. However, reaching high densities and a high number of elastic collisions are the two major challenges remaining to achieve quantum degeneracy with molecules. 4 molecules were laser cooled and trapped in the last decade, but recent experiments have shown universal loss upon collisions caused by the formation of complexes and therefore preventing further cooling. Although not yet fully understood, the loss is favored by the large state densities of the heavy diatomic molecules used so far. I propose a novel strategy: HeliUM aims to overcome both obstacles by achieving direct laser cooling of the lightest and first homonuclear molecule He2 and establishing a path towards quantum degeneracy. The light mass of the molecule, absence of hyperfine structure and a restricted set of rotational states due to the Pauli principle, drastically reduce the level density and facilitate evaporative cooling. Additionally, relying on a continuous molecular beam and implementing an innovative slowing technique will lead to densities several orders of magnitude larger than in existing experiments. With HeliUM, I will provide a controllable, simple 4-electron system at record low temperature, allowing quantum sensing and precision measurements to test quantum physics and the quantum nature of collisions with unprecedented accuracy - while being accessible to highly accurate ab initio computational methods. By using Rydberg states and photodissociation, HeliUM will put me at the forefront of measuring cross sections for a plethora of reactions involving charged and neutral, atomic and molecular helium species, relevant for understanding He droplets, astro- and plasma physics. This will complement my strong track record in precision measurements of molecular hydrogen and its ion.

Mots-clés : laser cooling,ultracold molecules,ultracold collisions,precision spectroscopy,rydberg spectroscopy,molecular physics,diatomic molecules,scattering
Projet ERC : NUCLEAR MIX (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université libre d'Amsterdam — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Arbuscular mycorrhizal fungi (AMF) form one of the most widespread terrestrial symbiosis on earth with the roots of plants, known as mycorrhizal symbiosis. Multiple AMF connect with multiple plants simultaneously forming large underground common mycorrhizal networks (CMN) where carbon and nutrients are exchanged. In contrast to most organisms where a single cell carries a single nucleus, a single AMF cell holds thousands of nuclei. This mysterious multinucleate and clonal biology has generated open questions in evolutionary biology. First, AMF have been called “evolutionary scandals” for supposedly surviving millions of years without sex, contradicting the theory that lack of sex in eukaryotes should lead to extinction. Second, their permanent multinucleate nature has generated debates about what defines an AMF individual.  My work, and others, recently demonstrated that AMF have a unique genetic organization, with some AMF containing - not one - but two genomes (nucleotypes). While we now know that variation in this genetic system exists, it is unknow: (i) how this genetic diversity is produced, (ii) whether this variation exists in absence of sexual reproduction, and (iii) whether this variation affects nutrient trade across mycorrhizal networks. By using high resolution molecular techniques, advanced microscopy, image analysis, and DNA/RNA fluorescence in situ hybridization, I will ask: What are the costs and benefits of nuclei mixing from single cells to across connected CMN networks? Working across three scales, I will test whether co-existence of two genetic nuclei groups result in sexual reproduction (WP1) how interactions affect the mycelia fitness of interconnected strains across CMNs (WP2) and how nuclei mixing affects plant response and plant community assembly (WP3). This work will challenge long held dogmas (AMF asexuality and network connectivity) and can help maximize the benefits of the mycorrhizal mutualism for agriculture.
Projet ERC : SymPathy (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université libre d'Amsterdam — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

By vectoring plant pathogens, herbivorous insects are key determinants in the epidemiology of numerous plant blights. For a vector-borne phytopathogen, natural selection favors upgrading insect fitness to enhance transmission to an uninfected plant. It is currently unclear how a microbe balances this dual symbiotic lifestyle, featuring markedly different interaction outcomes: as a plant pathogen and an insect mutualist. Likewise, little is known about the molecular mechanisms underlying pathogen specificity, and the genomic basis and consequences of cross-kingdom host shifts along the parasitism-to-mutualism continuum. I will tackle these questions using an emergent model system: the interaction between the fungal pathogen Fusarium, the leaf beetle Chelymorpha alternans, and their shared host plant Ipomoea batatas. I recently described that C. alternans associates with a fusarial strain that coats the pupae of its host, protecting beetles against predators during metamorphosis. In exchange, the insect propagates its symbiont to its host plant, where it causes wilt disease. The unique biology and tractability of this study system affords unparalleled opportunities for experimentation. My approach will combine fieldwork and bioassays, with the latest developments in sequencing technologies, reverse genetics and metabolomics to characterize (1) the mechanistic features of symbiont-driven defense, (2) the genetic basis of infection in a cross-kingdom host-shift, (3) the genomic consequences of a dual symbiotic lifestyle, and (4) the breadth, origin as well as partner fidelity and chemical stability of a pathogen-vector interaction. Bridging the fields of chemical ecology, plant pathology and natural product research, this project will significantly further our understanding of the genetic-basis of cross-kingdom symbiotic interactions and the epidemiology of plant pathogens.

Mots-clés : insect,fungi,host microbe interactions,phytopathogen,chemical ecology