Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SYNREG (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Hôpital universitaire de la Charité de Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Charité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

How the genome controls precise, cell-type specific gene expression is crucial for cell identity and differentiation. Short cis-regulatory elements, such as enhancers, are distributed in extended regulatory domains surrounding their target gene, which in mammals typically span hundreds of kilobases. Although all evidence indicates that gene regulation is controlled by the combined action of large domains, our current understanding mostly focuses on enhancers. If and how intervening DNA sequences, enhancer order, or spacing within regulatory domains contribute to gene regulation is unknown. The reason for this largely unexplored aspect lies in our limited ability to systematically alter large genomic regions. In this study, we will use recent advances in synthetic biology to overcome this limitation. From synthetic DNA, we will create variants of entire gene regulatory domains and integrate these into mouse embryonic stem cells. We will test synthetic regulatory domain function in tailored gene expression analyses using cell culture, organoid, and in vivo models. By investigating regulatory elements with respect to their surrounding regulatory domain, we will uncover hidden rules of gene regulation. In variant regulatory domains we will systematically assay understudied parameters, such as enhancer spacing, order, or inter-enhancer sequences. We will use single-molecule methods to measure gene expression level; use organoid and in vivo systems to profile cell-type specific changes in expression patterns, and we will use the unique potential of synthetic DNA to understand the fundamental link between DNA sequence and chromatin composition of regulatory domains. With this interdisciplinary approach, we aim to uncover previously hidden layers of genomic information. The insights generated from this work will provide a novel and unique view on the organization of the non-coding genome, with the potential to expand our ability to read and write genomic DNA sequences.

Mots-clés : gene regulatory landscape,synthetic dna,super enhancer,regulatory domain,enhancer interaction,genome engineering
Projet ERC : CHIPFRICTION (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Nederlandse organisatie voor wetenschappelijk onderzoek — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NWO
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Friction contributes to the global computer chip shortage: friction and wear limit the positioning accuracy and throughput in chip production. As future positioning requirements approach the atomic scale, contact, friction and wear need to be understood at this scale to inspire new positioning solutions which are more urgently needed than ever before.  CHIPFRICTION will focus on a key interface in chip production: carbon based material-on-silicon subjected to nanoslip in a hydrogen-rich environment. How nanoscale elasticity, plasticity and adhesion control rough contact formation will be revealed by matching contact models to ground-breaking fluorescence microscopy contact observations. How a local frictional stability criterion translates into the nanometre partial slip that characterizes the onset of multi-contact sliding will be modelled and observed through unique pre-sliding experiments. The oxidation, interfacial bonding and mechanical mechanisms that lead to wear of the carbon based material will be exposed through a combination of environmental control, new nanowear visualization methods and ex-situ XPS characterization. I am uniquely suited to conduct this work because I have fuelled the development of these experimental techniques, and I have experience in conducting the associated physical modelling.  Macroscopic friction emerges from generic physical ingredients such as elastic deformation of surface topography and shearing of interfacial covalent bonds. How friction emerges, creates a scientific challenge with major impact: Friction is responsible for 25% of the world's energy consumption. I will address this long-standing challenge by experimenting and modelling the complex interplay between contact mechanics, frictional slip and wear of the specific interface. The transfer of new friction manipulation strategies for chip production without friction is facilitated by having an institutional link to the lithography industry.

Mots-clés : in situ,interface,multiscale,adhesion,pre sliding,contact mechanics,wear,friction
Projet ERC : RUSTDEC (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Barcelona School of Economics — Pays : Espagne — Rôle : PI
Acronyme de l'entité : BSE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

A key feature of economic development is structural transformation characterized by spatial and sectoral labor reallocation out of agriculture. Despite clear evidence of rural-urban migration flows in developing countries, recent contributions show persistently lower productivity in agriculture compared to other sectors and large disparity in agricultural productivity across space. This points to the key question of this proposal: “why do so many workers remain in agriculture”? There is a pressing need for reliable answers to this question as rural areas host large shares of the population, facing high agricultural risk and poverty incidence. Any effective poverty eradication policy, such as those envisioned by the UN’s Sustainable Development Goals, must therefore necessarily focus on rural development. RUSTDEC will obtain novel answers to this key question by combining innovative micro panel data from Sub-Saharan Africa and Southeast Asia with an array of geospatial data on rural areas, exogenous variation in agricultural productivity, and quantitative theoretical models. The project employs remote-sensing and computer vision methods for generating community data as well as quasi-experimental and structural estimation techniques for rigorous causal estimation to pursue three major objectives: (i) provide first evidence on the role of dynamic adjustments in agricultural production for explaining the agricultural productivity gap and the magnitude of factor (mis-)allocation; (ii) dissect the microeconomic anatomy of spatial and sectoral labor reallocation and skill selectivity within and across rural communities; and (iii) identify the historic and future impact of climate change on agricultural production, adaptation, and rural development and its implications for the productivity gap. These objectives address three well-defined gaps in the literature, each going beyond the specific state-of-the-art and with the potential of generating ground-breaking impact.

Mots-clés : developing countries structural transformation rural communities agricultural productivity farm investment factor allocation labor reallocation skill selectivity migration climate change agricultural adaptation rural development
Projet ERC : MicroStars (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Centre de recherches énergétiques, environnementales et technologiques — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CIEMAT
Type d'entité : Recherche
Financement ERC de l'entité : 2473531.0 €

The universe in the visible wavelength remains largely unexplored in the sub-second time regime and sub-milliarcsecond scale, primarily due to instrumental limitations. Overcoming these impediments would bring a breakthrough in our knowledge of stellar physics, evolution and modelling by imaging the stars and their surroundings as well as unravel the history of the Solar System.  MicroStars will demonstrate the viability of a cost-effective and novel solution to enhance the capabilities of Imaging Atmospheric Cherenkov Telescopes (IACTs) to perform ultra-fast optical measurements. Such an upgrade allows two novel applications of these telescopes in the visible range: their use as Stellar Intensity Interferometers and as high-time-resolution, fast, high-precision photometers.  MicroStars will allow to expand the limiting time and angular resolution of current optical observatories by at least an order of magnitude. By upgrading the capabilities of next-generation IACTs, MicroStars has the potential of creating a host of scientific breakthroughs, answering fundamental questions regarding stellar physics, magnetic activity and modelling, exoplanet properties and the Solar System planetary formation. The interdisciplinary and field-transforming nature of MicroStars, merging astroparticle physics instrumentation with optical astronomy, will extend the scientific life of current IACT experiments, and greatly expand the scientific impact of the next generation: the Cherenkov Telescope Array. Bringing this proposal to life is only possible with an ambitious funding scheme, willing to finance the major equipment needed, and support a research team with the required multidisciplinary skills to expand the state of the art with novel instrumentation and methodologies.

Mots-clés : microarcsecond optical astronomy,imaging atmospheric cherenkov telescopes,planetary formation,stellar physics,kuiper belt objects
Projet ERC : TransLitigate (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Tilbourg — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1470849.0 €

Litigators feature in a crucial role as we confront the pressing global environmental governance challenges of the 21st Century. They possess an agency which is capable of driving the evolution and implementation of law across national boundaries and at the supranational level. This project proposes to develop a groundbreaking, explanatory model of transnational collaborations among strategic litigators which accounts for their modes of collaboration, how those collaborations affect their agency in controlling the issues in their respective fields, and how they negotiate complex ethical and professional challenges in their work. It proposes to develop this model through the combination of comparative doctrinal research and inductive qualitative socio-legal research across four case studies of strategic litigation: climate change, large-scale land transfers, pollution caused by extractives industries, and species conservation. It pursues the ground-breaking aim of explaining the multi-faceted and complex deliberations among transnational communities of litigators which give rise to and shape the landmark cases transforming environmental governance in diverse national contexts. With this contribution to the sociology of strategic litigators, the project will achieve a break-through in our understanding of how change can be initiated in legal systems to overcome perpetual obstacles and meet our global environmental challenges. It pursues a breakthrough in understanding how litigators drive states and their legal systems to act upon their ability to govern global environmental challenges, given the unlikeliness of it occurring through domestic and international lawmaking alone. In sum, the project aims to develop a groundbreaking model of an innovative type of agency and actor in global governance: the strategic litigator collaborating across borders.

Mots-clés : transnational law legal mobilization legal opportunity structures transnational social movements strategic litigation public interest litigation climate litigation environmental litigation socio legal studies
Projet ERC : SpatialTMEMetabolism (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Helmholtz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HGF
Type d'entité : Recherche
Financement ERC de l'entité : 1497756.0 €

The success of cancer immunotherapy, especially immune checkpoint inhibition (ICI), demonstrates the ability of the immune system to fight tumors. However, only a fraction of patients benefit from currently available therapies, and we need to find novel approaches to improve clinical responses. Cellular metabolism has emerged as a key determinant of multiple aspects of immune cell function, especially T cell exhaustion and anti-inflammatory macrophage polarization. However, we currently do not have a good understanding of the metabolic states of human immune cells since no technology has been available to quantify them directly in clinical tumor tissues. I hypothesize that tumors create spatially defined metabolic environments, also called metabolic niches, to suppress immune cells and that this mechanism can be targeted to improve cancer immunotherapy. To test this, we will (1) quantify the metabolic states of immune cells in solid human cancers, (2) identify metabolic immune cell states that predict response to ICI, and (3) reveal the mechanism of metabolic niche formation in tumor organoids. We will quantify cellular metabolism and phenotype directly in human tumor tissues, using the innovative single-cell metabolic profiling (scMEP) approach I have recently developed. We will combine this with multiplexed ion beam imaging (MIBI), a technology that enables 40-dimensional proteomic imaging. MIBI imaging will be complemented by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and machine learning frameworks for the analysis of these multi-omic datasets. Taken together, this project will uncover generalizable concepts of how different tumor entities influence the cellular metabolism of immune cells to modulate their function. The potential therapeutic targets that will emerge from this analysis could thus contribute to improved treatment options for various types of human cancer.

Mots-clés : immunology,imaging,cellular metabolism
Projet ERC : REGUBIOME (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Príncipe Felipe Research Center — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CIPF
Type d'entité : Recherche
Financement ERC de l'entité : 1496479.0 €

Bacteria from the gut microbiota constantly interact with a range of abiotic and biotic factors. Perturbations in these factors, such as nutrient depletion or exposure to exogenous microbes, require specific bacterial responses that involve tightly controlled gene expression changes. However, the transcriptional regulation mechanisms promoting such gene expression changes remain poorly understood despite their importance. REGUBIOME will characterize how responses to specific biotic and abiotic stimuli are regulated at the transcriptional level in two health-associated gut bacteria: one probiotic (Lacticaseibacillus rhamnosus) and one pathobiont (Fusobacterium nucleatum, previously linked to colorectal cancer). This project relies on combining experimental platforms of increasing complexity to systematically characterize the responses of these two bacteria to defined biotic and abiotic factors, and to evaluate how these responses impact host health. First, I will develop a novel high-throughput functional screening tool, coupling CRISPR interference, microfluidic platforms for single-cell isolation, and transcriptomic profiling of isolates. By applying this tool to in vitro monocultures, I will reconstruct the first-ever gene regulatory networks in these bacteria and identify mechanisms of response to different abiotic factors. Second, microfluidic co-culturing of these two strains with multiple other bacteria, coupled with metatranscriptomic profiling, will reveal the regulatory mechanisms mediating the interactions with other microbiome members. Lastly, in vivo work in mouse models will shed light on how the host colonic environment impacts gene expression in these health-associated bacteria. Altogether, REGUBIOME will provide proof of the importance of gut bacterial gene regulation networks to host health. Besides, by uncovering gene regulatory mechanisms in microbiome bacteria, REGUBIOME will provide novel actionable targets for microbiota modulation strategies.

Mots-clés : metatranscriptomics,crispr interference,host microbe interactions,gut microbiome
Projet ERC : BESSEL (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
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 : 1499973.0 €

Wireless medical devices can be implanted in the body to monitor health and to deliver therapies. Recent advances in biosensors, neural interfaces, biotechnology, microelectronics, and improved surgical techniques enable a vision of minimally invasive battery-free bioelectronic implants that can perform a wide range of medical and research tasks. Examples include biosensing for an early detection of health anomalies, recording and precision stimulation of central and peripheral nervous systems, implantable labs-on-a-chip, surgical microbots, and so on. A key scientific challenge lies in how these devices can be powered and controlled from outside of the body. Existing wireless solutions remain limited in their ability to transfer energy and data. These limitations result from the difficulty in controlling electro-magnetic waves in the human body – a dynamic, heterogeneous, and lossy medium. The objective of this proposal is to develop bio-adaptive wave control technologies that overcome these challenges to enable efficient powering and precise control of mm/μm-scale deep-body bioelectronics. To accomplish this, we will (1) focus on the fundamental studies of waves and their control in complex and dynamic anatomical media; (2) develop new reconfigurable architectures of conformal radiating surfaces for the practical implementation of the developed wave control methodologies, and (3) demonstrate clinical utility by fully wireless recording and modulation of the pancreatic nerve activity in an anesthetized porcine model through dynamic wave control. The proposal relies on interdisciplinary track-record of the PI in bioelectronics and neural interfaces, wave physics and computational electromagnetics, conformal radiating structures and wireless power transfer. BESSEL consolidates these skills and enables conducting research on highly capable deep-body wireless bioelectronics with high translational potential.

Mots-clés : implantable devices,wireless bioelectronics,wireless power transfer,wave control devices,conformal radiating structures
Projet ERC : DynaMorph (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
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 : 1499601.0 €

Transforming a flat plate into a doubly curved shell is not possible without distorting in-plane distances, as stated by Gauss in his seminal theorem. In natural morphogenesis, this strong geometrical constraint is overcome by differential growth in the tissues, which induces mechanical stresses and thus the buckling in a rich variety of shapes. Over the last decade, emerging approaches have embraced this paradigm to develop bioinspired synthetic responsive materials with in-plane distortions, and hence shape-morphing capabilities. However, despite rapid developments, current efforts primarily focus on programming the final equilibrium shape, overseeing the dynamical trajectory of the transformation but also the mechanics of the morphed structure. As a result, exciting biomedical applications perspective in minimally invasive surgery, rehabilitation and soft robotics remain so far elusive.  Here, I aim to develop structures in which the shape, but also the mechanics and the dynamical deformation trajectory may be programmed in time. To do so, I propose to develop hybrid elastic plates embedding a network of fluid-filled cavities. First, I will generalise design principles to create unit cells that dispose of all six deformation modes (both in-plane and out-of-plane) when pressurized. Assembling such cells will enable univocal shape selection but also internal degrees of freedom to control the frustrated mechanics. Then, I will unravel the coupling between fluid viscosity and cavity geometry to spatially control the homogenized viscoelastic property of the material. The subsequent timescales will be finally used to program the dynamical deformation trajectory of the structure when submitted to a mechanical or fluidic load. Taken together, I propose to develop new experimental standards and theoretical frameworks to pave the way for the first fully controllable shape-morphing materials, with applications for adaptive peristaltic endotracheal cuffs in view.

Mots-clés : shape morphing,slender structures,mechanical instabilities,incompatible elasticity