Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
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 national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1025355.0 €

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 : CHORUS (Horizon Europe, appel 2021, 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 : 1479242.0 €

Fluid flow in porous media plays a central role in a large spectrum of geological, biological and industrial systems. Recent advances have shown that microscale chemical gradients are sustained by pore-scale chaotic flow dynamics. This fundamentally challenges the current macrodispersion paradigm that assumes that porous transport processes occurs under well-mixed microscale conditions. Using novel experimental, numerical and theoretical approaches, CHORUS will explore the origin, diversity and consequences of chaotic mixing in porous and fractured media. For this, the team will develop a new generation of imaging techniques coupling laser induced fluorescence, refractive index matching and additive manufacturing of complex and realistic porous and fractured architectures (WP1 and WP2). The CHORUS team will use these insights to develop new modelling concepts for describing scalar mixing and dispersion in microscale (WP3) and multiscale (WP4) systems. Building on these experimental, numerical and theoretical breakthroughs, CHORUS will design “smart” porous flows with porous architectures that selectively optimize mixing, dispersive or reactive properties (WP5). CHORUS will thus develop a new paradigm for transport dynamics in porous and fractured media, with far-reaching applications for the understanding, modelling and control of a range of natural and industrial processes, including contaminant transport and biogeochemical reactions in the subsurface, CO2 sequestration, membrane-less flow batteries, flow chemistry, chromatography or catalysis.

Mots-clés : porous media,transport,mixing,dispersion,fractured media,lagrangian chaos
Projet ERC : GUARDIANS (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Research Institute of Molecular Pathology — Pays : Autriche — Rôle : PI
Acronyme de l'entité : IMP
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1500000.0 €

Successful pathogens use virulence factors to inhibit immune defenses. To counteract this, host guard proteins monitor the integrity of pathways (‘guardees’) that are attacked by virulence factors, such that inhibition of the guardee activates guard-driven immunity. Instead of directly detecting microbial components like canonical innate immune (pattern recognition) receptors, guards are activated by sensing the activity of virulent microbes. While guard-immunity is common in plants, only a few mammalian guard-pathways are known and mammals are thought to heavily rely on pattern recognition to detect pathogens. We have recently described the MORC3-MRE pathway, the first mammalian guard-sensing pathway that recognizes the virulence- associated activity of viruses to induce a protective interferon (IFN) response. I hypothesize that mammalian guard-sensors are highly relevant for both immune homeostasis and immunity and propose to test this hypothesis by focusing on the MORC3-MRE pathway. Utilizing genetic approaches in human monocytes and mice, we will reveal novel components and molecular mechanisms of the MORC3-MRE pathway and investigate its role in homeostasis and immunity in vivo. The main hypothesis of this proposal is that guard- sensing allows mammalian immune cells to broadly recognize the activities of virulence factors. We aim to conduct forward genetic screens in human monocytes to identify virulence-associated activities of pathogens that are sensed by the immune system. Functional genomics and biochemical approaches will identify the attacked guardee, the guard-sensor and molecular mechanism of guard-sensing. In summary, we will experimentally test the novel concept of guard-immunity in mammalian immune defenses. These experiments will generate fundamentally new insights into molecular mechanisms of pathogen recognition and will significantly broaden our understanding of innate immunity and host-pathogen interactions.
Projet ERC : CATES (Horizon Europe, appel 2021, 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 : 1499965.0 €

Forests cover a third of the vegetated surface of the Earth and interact with global climate. These interactions are being altered by human activities at an unprecedented scale, both in their rate and in their geographical extent. At present, Earth system models (ESMs) struggle to predict how these climate-vegetation interactions will evolve in the future because of varied responses of the carbon cycle in their Land Surface Models (LSMs). This long-standing issue leads to widely varying atmospheric CO2 concentrations and hence varying climate projections under the same scenarios. LSM projections of forest biomass and carbon balance increasingly diverge over longer periods, thus limiting confidence in future climate projections. The goal of this proposal is to develop a new cross-disciplinary framework to constrain climate projections by jointly improving the simulation of forest growth and water use efficiency (WUE; the ratio of photosynthesis to transpiration) at long time scales (decades to century) using novel observational standards for historical growth and physiology derived from tree-ring data. The following three objectives are addressed: (1) advance the mechanistic representation of tree-ring growth and stable isotopes in the global LSM ORCHIDEE, the terrestrial component of the IPSL ESM; (2) use tree-ring data together with eddy covariance flux measurements to improve the capability of the model to simulate the effects of changing climate, CO2 and nitrogen on forest growth and WUE; (3) provide the first climate simulations until 2100 constrained by historical forest responses. The constrained projections will reduce uncertainties on the feedbacks of altered tree growth and physiology on climate. The proposed work will bring into Earth System modelling decades of advances made by dendrochronologists around the world, providing at last a critical long-term constraint for the land surface modelling community as ice-cores are for global circulation models.

Mots-clés : land surface models,ecosystem modelling,forests,climate change,dendrochronology,stable isotopes,tree rings
Projet ERC : BeaT-IT (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : University Hospital Aachen — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UKA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1488762.5 €

Recent clinical evidence points to a potential new direction in immuno-oncology: utilizing B cells and B cell-associated tertiary lymphoid structures (TLS). B cells display diverse immunological actions, including antibody production, antigen presentation, cytokine secretion and TLS induction. They have a dual role: they can initiate and reinforce anti-cancer immunity but B cells can also acquire regulatory phenotypes. To open up a new immunotherapeutic paradigm, I aim to understand how to optimally activate B cells, using nano-/biomaterials which load and precisely release a variety of agents to stimulate B cells and to suppress B cell regulatory phenotypes. Furthermore, I will manufacture porous scaffolds based on injectable microgels or via 3D printing with microgel fibers to induce TLS formation. The scaffolds with tunable porosity will allow B cells and other immune/stromal cells to infiltrate, arrange and expand, and soluble factors to diffuse. Moreover, the scaffolds can be easily functionalized with different chemical cues to stimulate B cells for TLS formation, such as CXC-chemokine ligand 13 and interleukin-7. This will help us understand TLS induction. Importantly, I will use ex vivo engineered TLS to study what microenvironmental factors influence their functionality. Subsequently, in vivo formation of B cell-associated TLS will be induced by the scaffolds. B cell activation and TLS induction will be combined for tumor therapy, and potential abscopal effect of the treatment to address metastases will be studied. The materials will be further combined with checkpoint inhibitors and chemotherapy to reach synergism. In addition, the new therapeutic strategies will be tested in patient-derived tumors established in humanized mice. BeaT-IT aims to understand optimal B cell activation and TLS formation with nano-/biomaterials to establish a new direction in immuno-oncology, which is anticipated to realize an upcoming breakthrough in cancer immunotherapy.

Mots-clés : immunomodulatory nano biomaterials,cancer nanomedicine,tertiary lymphoid structures,drug delivery,tumor targeting,combination cancer therapy
Projet ERC : SecuStack (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
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 €

Problem: Side-channel leaks via timing, cache, and speculation can expose sensitive information across traditional isolation barriers, putting our data at risk. Unfortunately, despite decades-long attempts to eliminate these leaks, new attacks are discovered by the day. Fundamentally, this is due to the following mismatch: Today's hardware is extremely complicated because of its myriad fast paths and performance optimizations, yet, we reason about it based on coarse, implicit, and inaccurate models. This divide between model and reality results in leaks and inefficient systems that fail to keep our data safe. Aim: SecuStack wants to put an end to this seemingly endless cycle of new attacks and defenses through a radically new approach based on the following insight: To effectively secure computer systems against side-channel leaks, we need to know when the hardware leaks, at the level of gates, flip-flops, and wires. Approach: SecuStack will leverage this insight via the following four research tasks. First, the SecuStack team will automatically construct per-processor, ground-truth leakage models at the hardware level (T1). Next, we will use those models to describe leakage at the assembly (ISA) level (T2), which in turn will allow us to synthesize provably correct software defenses (T3). These steps build on research breakthroughs from my recent work. To remain feasible for a small team in a five-year timeframe, SecuStack will not target legacy toolchains but instead aim for a breakthrough in a tightly controlled setting, based on open-source RISC-V processors and a custom compilation toolchain. Finally, we will demonstrate immediate practical impact by implementing two challenging case studies: a silicon root of trust and an enclave monitor (T4).  Impact: If successful, this ambitious effort will yield the first provably secure end-to-end timing, cache, and speculation safe systems and pave the way towards secure infrastructure for the future.

Mots-clés : formal methods security side channels verification speculative execution attacks spectre attack hardware semantics hardening type system
Projet ERC : BayCause (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Université libre d'Amsterdam — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1185995.44 €

Causal conclusions are at the center of research, yet notoriously difficult to obtain. Many research studies report correlations only, which, in line with the maxim, do not imply causation. With correlations, one can make predictions. With causation, one can intervene. Paradoxically, causal inference can become harder when more data becomes available. In the by now increasingly common high-dimensional settings which are the focus of this proposal, including all variables is impossible while including too few can severely bias results. Variable selection becomes necessary, yet available methods are in short supply. My aim is to develop Bayesian nonparametric methods and theory for high-dimensional causal inference. Bayesian nonparametrics is eminently suited for variable selection in causal inference, because it excels at both incorporating and describing uncertainty. Recent theoretical advances, in particular in Bernstein-von Mises theory and high-dimensional nonparametric regression, have now finally opened up causal inference to Bayesian nonparametric approaches. I will investigate high-dimensional versions of the two most important causal frameworks, based on unconfoundedness and directed acyclic graphs. I will focus on novel aspects scarcely available in the literature, including uncertainty quantification, a broad range of data types, and nonlinear relationships. My expertise in causal inference, Bayesian nonparametrics, variable selection and survival analysis puts me in a unique position to work on this multifaceted challenge. My dual track in theoretical and applied statistics enables me to identify the problems which have highest priority in practice and are mathematically interesting. The novel methods with solid mathematical statistical foundation resulting from this proposal will tremendously expand the now limited settings in which trustworthy high-dimensional causal inference is possible, with applications in medicine, economics and many other fields.

Mots-clés : causal inference bayesian nonparametrics variable selection uncertainty quantification potential outcomes directed acyclic graphs survival analysis
Projet ERC : ELECTROPHOBIC (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
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 : 1357500.0 €

The last two decades have seen an explosion of scientific interest in hydrophobic solvation due to its stunning importance for biology, catalysis and environmental science. However, it is only recently that we realized how important hydrophobicity is for electrochemical interfaces. There, hydrophobic molecules are involved in key electrochemical reactions, such as water splitting and CO2 reduction for renewable energy technologies. Identifying and predicting hydrophobic solvation contributions to thermodynamics is expected to advance our comprehension of these processes, unlocking new ways to improve their efficiency. This can only be achieved through a substantial advance in theoretical understanding. The Lum-Chandler-Weeks theory that revolutionized our comprehension of hydrophobic solvation does not hold true at electrochemical interfaces. A change of paradigms is needed: first, the present theory is based on density fluctuations in the liquid bulk, but these are modulated by surface and applied potential at the interface; second, it is not only the solute size, but a combination of size/shape/position that matters at the interface. Developing a theoretical model from these new paradigms is the challenge tackled by ELECTROPHOBIC. The breakthrough will be to predict hydrophobic contributions to many electrochemical processes with my model. To start, I will focus on how hydrophobic solvation contributes to two problems that currently plague water splitting and CO2 reduction at metal-aqueous interfaces: the undesired aggregation of H2 molecules into interfacial bubbles and the selectivity toward multi-carbon products, respectively. Tremendous advances in the theoretical understanding of these reaction mechanisms and on the role of the electrode catalyst have been made by density functional theory calculations. I will couple these calculations with my model in a hybrid scheme such that surface and solvation contributions are simultaneously but separately evaluated.

Mots-clés : hydrophobicity,solvation,reactivity
Projet ERC : QPROJECT (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Institute of Mathematics — Pays : Pologne — Rôle : PI
Acronyme de l'entité : IMPAN
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1033125.0 €

This project is in the field of geometric measure theory (GMT), an area of analysis seeking to solve geometric problems using the tools of measure theory. A classical line of research in GMT concerns estimating the size of orthogonal projections of planar sets, and the most important results in this topic are the projection theorems of Besicovitch and Marstrand. In the last few decades, it became increasingly clear that obtaining stronger, more quantitative projection results is connected to open questions at the intersection of GMT, complex analysis, harmonic analysis, and additive combinatorics. The main goal of this project is proving quantitative projection results, with special focus on three concrete questions. The first is Vitushkin's conjecture from 1967. One of the key objectives of QPROJECT is completing the solution to this conjecture by showing that removable sets for bounded analytic functions have Lebesgue-null orthogonal projections in almost every direction. This will be achieved by proving a quantitative Besicovitch projection theorem. The second question this project aims to answer is an old conjecture of Besicovitch about the radial projections of purely unrectifiable sets.  The plan is to solve these two problems using the tools of quantitative rectifiability, and it is the right time to tackle them due to the PI's recent solution to a closely related conjecture of David and Semmes. The new techniques introduced in that work, such as the directional stopping time arguments, are likely to lead to breakthroughs on the two old questions.  The third problem is the visibility conjecture from fractal geometry, which is closely related to quantifying Marstrand’s classical slicing theorem. Building on the PI’s earlier work on this conjecture, the key to the full solution will be proving lower bounds on incidences in multiscale incidence geometry.

Mots-clés : quantitative rectifiability,uniform rectifiability,favard length,besicovitch projection theorem,analytic capacity,vitushkin s conjecture,painleve problem,besicovitch s radial projections conjecture,fractals,visibility conjecture,marstrand s slicing theorem
Projet ERC : ETRANHET (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
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 : 1472313.0 €

Economic ideas play a vital role in public decision-making. The energy sector is an emblematic case: competition policies (e.g. anti-trust laws, deregulation), taxation, emission permits and sustainable-growth programmes all have origins rooted in economic reasoning. Today, more than 80% of the world's primary energy comes from fossil fuel combustion, contributing strongly (75% of CO2 emissions) to climate change. To understand the historical developments that led to this situation, an in-depth examination of past economic discourses, concepts, theories, models and policy recommendations is essential. This has not been done to date. ETRANHET's ambition is thus to write the first ever history of energy transitions in economic thought, on a global scale. ETRANHET will analyse how economics has dealt with energy issues and transitions since the early 19th century, in diverse market-economy contexts (5 areas: Continental Western Europe, the British Isles, North America, Latin America, Japan). Deliberately going beyond the English-speaking literature, it will perform an unusual decentring of the history of economic thought. ETRANHET aims to characterise the context-dependency of past economic views of energy. It seeks to uncover forgotten, yet relevant, ideas that could enrich current research into the energy transition. And it intends to precisely determine how the economic discipline has been able to influence decision-making in energy matters. ETRANHET is a multidisciplinary project mobilising historiographical and science studies methods to study past economists and economic thinking. Digital humanities and archival research will be key, including the creation of electronic repositories, making new valuable material available to historians. By taking a fresh look at today's challenges in relation to the low-carbon transition, ETRANHET will contribute to show that the history of ideas has a role to play in contemporary debates on sustainability.