Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MagicSpore (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999671.0 €

How totipotency is established in germ cells is an essential question in reproductive biology. In the plant male germline, the haploid meiotic products – microspores – are totipotent, which permits crop breeding via microspore embryogenesis. However, the molecular basis and biological significance of microspore totipotency are unknown. More generally, our understanding of plant cell totipotency is in its infancy. My lab established the Arabidopsis male germline as a model to study germline epigenetic reprogramming. We recently discovered that H3K27me3, a histone modification essential for developmental regulation, is globally erased in microspores. We also identified a new family of histone H2A deubiquitinases (GDUs), and our results suggest that the GDUs and a histone H3 variant (H3.15) gradually remove H3K27me3 during microspore development. I hypothesize that global H3K27me3 erasure facilitates the diploid to haploid transcriptional shift, establishes cellular totipotency, and allows the two identical sperm cells within a pollen grain to initiate the development of distinct seed structures (embryo and endosperm). We will leverage our recent discoveries, as well as state-of-the-art technologies, to study in-depth the epigenetic basis of microspore totipotency and its biological functions, via these aims: 1) determine the timing, scope and functions of H3K27me3 reprogramming in microspores; 2) understand the role of histone H3.15 and GDUs in H3K27me3 reprogramming; 3) alter microspore regeneration ability by manipulating H3K27me3 reprogramming; 4) elucidate the contribution of global H3K27me3 erasure to double fertilization. Our outputs will revolutionize our understanding of plant cellular totipotency and sexual reproduction, and elucidate novel strategies to enhance microspore embryogenesis in recalcitrant crops. These insights will in turn reveal core principles governing epigenetic regulation of sexual reproduction in eukaryotes.

Mots-clés : germline,epigenetic reprogramming,chromatin,polycomb,microspore,arabidopsis
Projet ERC : MYCinTOPshape (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1996750.0 €

Inhibitors of DNA topoisomerases (TOPs, TOP1, TOP2) are mainstays of anticancer therapy. While they have proven effective, the toxicity of current TOP drugs, caused by DNA damage-induced apoptosis of non-cancer cells, limits their use in clinic. Development of tumour-specific TOP inhibitors will require a better knowledge of the mechanisms of TOPs. This research program aims to define how TOP are regulated during transcription and replication and develop drugs that target these regulatory mechanisms for anticancer treatment.  TOPs promote transcription and replication by removing DNA supercoiling generated during polymerase elongation. In my works published in Cell and Molecular Cell, I have discovered that the activity of TOPs in the cell is regulated. The oncoprotein MYC joins TOP1 and TOP2 in a topoisome complex and stimulates their activities to remove the supercoiling produced during transcription and replication, thus boosting cellular proliferation. Therefore, I propose that targeting the mechanism of the topoisome instead of the single TOPs, will selectively halt MYC oncogenic function while preserving physiological TOP activity, avoiding the generation of DNA damage associated to current TOP drugs. By using new genomic tools to analyse DNA topology, advanced biochemical and microscopy approaches, as well as drug screens, I will define the mechanism of MYC-driven transcriptional/replicational acceleration via topoisome assembly, and develop drugs blocking topoisome activity to arrest tumour growth. I predict this proposal is feasible based on my excellent background, compelling preliminary data, and strong collaborations with scientists at KI and National Institutes of Health. The work will identify novel strategies to target TOPs that can be put forward in clinical trials for the benefit of society. This new way of targeting TOPs to affect MYC activity constitutes a beyond the state-of-the-art and ground-breaking approach to the field of cancer biology.

Mots-clés : topoisomerases,dna topology,myc,anti cancer drugs
Projet ERC : SAFER (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Chemical health risk assessment has failed to safeguard fertility in women. Women and their oocytes are exposed to pervasive mixtures of human-made chemicals that correlate with reproductive ageing and infertility. Only 0.5% of the chemicals on the European market have been well characterized for health risks, and reproductive toxicity in women is typically not covered due to missing tools. The new European Growth Strategy aims at sustainable growth, zero-pollution and safe chemicals. While the need for increased chemical testing is tangible, there is a movement to phase out animal experiments. This creates a huge challenge to deliver on the vision of a safe and toxic-free environment. Here, I will develop new high-content assays for reproductive toxicity in women. SAFER is built on my exceptional ovary biobank, established stem cell lines, and multi-omics technologies. Using chemically exposed ovarian tissue and stem cell derived blastoid cultures, SAFER will map mechanisms mediating toxicity by high-resolution epigenetic and transcriptomic analyses. Model chemicals are chosen based on ubiquitous presence in women and significant associations to decreased ovarian function, as shown by my cohort studies. The identified mechanisms will be tailored into reporter genes that I will insert into new immortalized human ovarian cells as well as stem cells, and develop into high-content screening assays. The product of SAFER is novel in vitro tools for screening of female reproductive toxicants.  Taken together, SAFER sets an example for animal-free derivation of assays for chemical safety assessment. SAFER tools will contribute to identification and restriction of chemicals that pose a hazard to women’s health. This is an important step in the global movement towards a non-toxic, safe environment.  Starting a family is a basic human right, and whether to have a child or not should be decided by the prospective parents, not by the chemicals in their environment.

Mots-clés : reproductive toxicology,human made chemicals,endocrine disrupting chemicals,non toxic environment,infertility,female fertility,human ovaries,human embryos,human stem cells,human ovarian tissue culture,ovarian follicles,ovarian reserve,oocyte,organoid,blastoid model,implantation,single cell multi omics,mechanisms,reporter genes,in vitro assays,cell culture,high content assay,chemical health risk assessment
Projet ERC : CoDiNA (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1936503.0 €

Modern numerical algorithms and high performance computing systems are capable of simulating physical systems far more efficiently than those from just few years ago. However, this recent increase in computational power comes with an insatiable demand for complexity and scale: scientists and artists now wish to model textiles at the level of individual fibers and simulate oceans down to the smallest ripple. The typical strategy of analytically deriving integrators and hand-tuning parameters will inevitably fail to cope with the increasing non-linearity and complexity of these problems. This shift in problem complexity necessitates entirely novel strategies for discovering numerical algorithms.  We will redefine the state of the art in numerical simulation and animation by combining three different approaches: First, we will develop analytical tools customized for large scales; we will derive optimal numerical algorithms by viewing physics through the lens of computational complexity, and by observing limiting behaviors as problems increase in size. Next, we will gain physical insights by simulating huge numbers of smaller simulations and generating large data sets. By discovering trends in this data, we will faithfully approximate aggregate behaviors in systems that are far too complex for analytical techniques to penetrate. Finally, by framing the derivation of numerical algorithms as a constrained optimization problem, we will be able to deliver provably optimal code for a given piece of hardware and precisely control accuracy/efficiency trade-offs.  The combination of these research directions will enable efficient simulations of massively complicated systems that are currently unfeasible to compute. Due to the timely and groundbreaking nature of these proposed directions, we also expect to develop entirely unprecedented methods for physics simulation and discover a number of theoretical insights and scientific advances along the way.

Mots-clés : physics based animation,fluid animation,fracture animation,numerical algorithms,numerical homogenization
Projet ERC : REGCORD (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1993094.0 €

How the organs of a developing organism achieve their correct size and shape is a fundamental unresolved question in biology. Mammalian embryos possess a remarkable ability to regulate (restore) the correct size of their tissues and organs upon perturbations during early development, yet how this is achieved is unknown. Addressing this question has so far been challenging because it requires a multiscale approach that integrates precise measurements with theoretical frameworks. We are now in an excellent position to unravel the mechanisms by which the mouse spinal cord regulates its size and shape during development by building on our experience with quantitative studies in this system. We previously obtained quantitative spatiotemporal data of growth, pattern and morphogen signalling dynamics in the spinal cord. We showed that there is a critical period during which morphogen signaling is interpreted to specify cell fates, uncovered a mechanism that allows precise pattern formation, and identified a link between the growth rate and tissue anisotropy. Our expertise now enables us to address the following new questions: 1) how is size regulation in the spinal cord achieved at the tissue and cellular level; 2) what is the molecular mechanism of size regulation, in particular the role of morphogen signaling; 3) how is the regulation of spinal cord size linked to the regulation of its shape. To address these questions, we will combine precisely controlled ex vivo assays in organoids and whole embryo culture, and in vivo advanced mouse genetics and mosaic analysis. We will obtain highly resolved dynamic data and interpret it in the context of rigorous theoretical frameworks. The project will advance our understanding of the fundamental mechanisms of tissue size control and the constraints they impose in regeneration and disease. Our results will have implications for in vitro tissue engineering and research on multi-organ coordination and robustness during development.

Mots-clés : tissue growth neural tube morphogen gradient biophysical models of development
Projet ERC : ID-SCAPES (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Institut de Recherche et d’Innovation en Santé de l’Université de Porto — Pays : Portugal — Rôle : PI
Acronyme de l'entité : i3S
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999493.0 €

The cultural heritage associated with India and Bangladesh’s Christian minorities remains understudied and its historical significance is often contested. Many of the countries’ medieval and early modern churches were built primarily for communities of newly converted Christians that came from different regions and caste backgrounds and therefore carried corresponding identities. Even today, many of South Asia’s churches reflect these local identities and traditions, with factors such as caste, “indigenous” agency, and cultural “accommodation” playing a role in their social and architectural history. These contexts originated distinct regional architectural expressions in the countries’ six main Christian ethnolinguistic communities (East Indians, Goans, Mangaloreans, Keralites, Tamils and Bengalis) However, most scholarly work has addressed the design of these churches against the background of European artistic tendencies - such as mannerism or baroque - while local contexts and traditions have remained overlooked. Today, as dominant groups assert hegemonic policies across South Asia, religious minorities face increasing challenges, and their cultural heritage is oftentimes at risk. Many of South Asia’s churches founded before ca. 1800 have disappeared, are in ruins or have been deeply transformed, and there is a sense of urgency in documenting the churches that remain. ID-SCAPES will produce a Social History of the Built Environment of India and Bangladesh’s medieval and early modern churches and sacral landscapes, uncovering the influences of diverse agencies, identities and traditions on their overall design. By producing knowledge on this body of architecture, with in-depth analysis providing vision for contested and/or endangered sites, the project will ascertain how churches are vital in framing the collective identities of Christian minorities today, thereby nurturing their resilience and contributing towards the diversity of South Asia’s cultural heritage

Mots-clés : cultural heritage early modern history entangled histories caste
Projet ERC : FISH-A (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Institut de Recherche et d’Innovation en Santé de l’Université de Porto — Pays : Portugal — Rôle : PI
Acronyme de l'entité : i3S
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2001468.0 €

To what extent can fish produce architecture? This project sets out to trace a socioecological history of North Atlantic architecture in relation to fisheries, elucidating the relationships between marine environments and terrestrial landscapes and assessing the ecological impact of fishing constructions and the natural resources they depend upon. Fishing Architecture covers a broad spectrum in terms of both geography and time, a choice that was made to avoid deterministic analysis and engage with transnational phenomena. Thus, the focus is on the North Atlantic—its shores housing diverse architectural cultures and its waters home to a wealth of fish species—and follows a time frame that runs from the industrialization of fisheries in the early 19th century to the full globalization of the industry at the end of the 20th. The extant scholarship on marine ecology, fisheries, and fishing communities includes extensive research on fish populations, navigation systems, technology, bioeconomics, architecture, and cultural practices. Yet, comprehensive interdisciplinary analysis of the field is hindered by its own specialization. Facing the impending challenges of the environmental predicament, this project will use the material history of architecture as a powerful tool for advancing interdisciplinary research and, along with it, our understanding of the ecological impacts of human activity. The assessment will be organized along five analytical axes: (1) marine ecosystems; (2) fishing technology; (3) food processing; (4) politics; and (5) consumption habits, effectively avoiding the conventional architectural approach to understanding the built environment. This strategy allows us to identify critical knowledge gaps to be worked on and, most significantly, fosters a fresh perspective on construction in which fishing landscapes and buildings are understood as material traces of dynamic socioecological relationships and as part of the continuum between land and sea.

Mots-clés : architecture marine ecology fisheries sea land continuum ecosystems environmental history bioeconomics nature based solutions social ecological systems oceanography coastal communities
Projet ERC : RAW (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Studies of Cultures and Arts
Entité participante : Institute of Ethnology — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : EÚ AV ČR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998958.0 €

Existing scholarship has highlighted disparities in the adverse consequences of armed conflicts, forced displacement, and peacebuilding on Romani communities, which feed on and exacerbate prior patterns of marginalisation, racism, and dispossession. Yet there is a notable lack of longitudinal research on lived Romani experiences of war, forced displacement, and post-war reconstruction—despite the presence of Romani people in every European and Middle Eastern country that has witnessed war over the last three decades. Virtually nothing is known about how Roma have maintained families, kinship networks, and community cohesion, or about the traces left by wars within Romani social life. The project provides the first systematic and comparative study of its kind, grounded in the observation that extant ‘peacetime’ research evinces kinship as the prime mechanism through which Roma create spaces of liveability and fashion social belonging in a way that is not overdetermined by their unequal relationships with non-Roma. Through immersive research with Roma from Ukraine, Iraq, Syria, and former Yugoslavia, this innovative ethnographic project investigates the transformations of Romani kinship in the wake of conflicts. It explores how kinship practices and relations are mobilised as a social resource for enduring the effects of wars, as well as how wars become inscribed in the kinship form. By examining everyday acts of care, changes in relatedness networks, and Romani generational thought, the project offers a unique approach for understanding the social dynamics of war and its aftermath from the viewpoint of a vulnerable, dispersed, and territorially non-contiguous ethnic minority, going beyond the analysis of majority realities. By analysing the ‘plasticity’ of kinship and its constraints within the extreme context of wars, the project’s broader aim is to advance our understandings of how social vulnerability, adaptation, and socio-cultural continuity are interwoven.

Mots-clés : war romani people family violence exhange kinship networks racism
Projet ERC : TOP-GUN (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
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 : 2000000.0 €

From antiparasitic toxins in butterflies to antifreeze proteins in fish, horizontal gene transfer (HGT)—the non-sexual exchange of genes between species—has been observed in all major eukaryotic lineages. However, one of its most fascinating aspects, the transfer mechanism, remains a mystery despite decades of research. How can DNA leave the donor species, come in close contact with the germline of a second species, and integrate in the genome of its new host? Our lab made a significant breakthrough in our understanding of this process that now allow us to address these questions experimentally. We discovered that Mavericks, ancient eukaryotic transposable elements related to giant viruses and adenoviruses, have mediated the widespread transfer of genes between highly divergent nematode species on a global scale. The gene content of Mavericks suggests that they have a dual lifestyle: both as transposons and as infective enveloped viruses. Yet how they accomplish HGT at the molecular level is unknown. Having pioneered the identification of the first HGT vector in animals, the objectives of the TOP-GUN proposal are to dissect the molecular basis of HGT, elucidate its impact on evolution, and reveal general principles of HGT across eukaryotes. To achieve this, I propose the following aims:  1. To uncover the life cycle of Mavericks and reconstitute Horizontal Gene Transfer in the lab 2. To dissect the impact of Mavericks and their cargos on molecular innovation and genome evolution 3. To systemically discover vectors of Horizontal Gene Transfer across eukaryotes in silico  My team and I will pursue these objectives by applying a multidisciplinary approach combining genetics, functional genomics, biochemistry, and structural biology. We believe that TOP-GUN will ignite HGT as a new experimental research field and catalyse the development of new payload delivery systems for parasitic nematodes, most of which cannot be genetically modified due to their complex life cycle

Mots-clés : horizontal gene transfer,selfish genetic elements,genomic conflict,toxin antidote element,transposons,gene drive,evolution of novelty