Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet DeepGlue (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Interactions between proteins and small molecules are rich in nature – across organisms, tissues and cellular contexts they underly crucial biological functions in health and disease. One class of small biochemicals, molecular glues (MGs), can selectively induce de novo protein-protein dimerization. Particularly in the context of targeted protein inhibition and degradation, MGs are praised as clinical alternatives to treating diseases driven by proteins that are otherwise pharmacologically intractable. Prominent examples like rapamycin, a MG used in the therapy of kidney tumours, illustrate a key research challenge, however: up until now, most MGs have been discovered by chance. Our limited understanding of their biophysical characteristics prevents us from rationally designing MGs, and from tracing drug resistance mechanisms by target proteins’ mutational escape during cancer evolution.  Here, I propose a scalable experimental strategy to determine the binding profiles of MGs to thousands of target protein mutants in parallel. To perform comparisons of the biophysical impact of mutations on distinct MG mechanisms, I have three major aims: 1.) to develop a deep mutational scanning assay to quantify MG-protein-protein complexation, 2.) to produce the first global atlas of resistance mutations for a classic MG system – rapamycin in complex with MTOR and FKBP12, and 3.) to characterise ABA, a plant hormone which induces heterodimer formation by extensive structural remodelling of only one of its target proteins.  “DeepGlue” will take place under the experienced supervision of Prof. Ben Lehner (CRG Barcelona), whose group has pioneered the use of deep mutagenesis to understand protein structures, dynamics and interactions. Within this environment, my action will be uniquely positioned to transcend the dynamic fields of Chemical Biology, Protein Biophysics and Cancer Evolution – aspiring to deliver fundamental insights that ultimately shape new and better therapies.

Mots clés : deep mutational scanning, molecular glue, drug resistance, protein protein interactions, chemically induced proximity

Participants :
- Centro de Regulación Genómica (Espagne) — Coordinator, beneficiary, Recherche, subvention : 181152.96 €
Projet HETERO-EVO (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Chromatin functionally organizes all eukaryotic genomes. Genomic regions within heterochromatin are transcriptionally repressed and aberrant expression can be lethal. Heterochromatin is characterized by specific histone modifications, but reader-repressor proteins are directly responsible for preventing DNA-templated processes. Recent studies suggest immense functional diversity of reader-repressor proteins that remains poorly understood. Understanding this diversity will reveal the ancestral composition and capabilities of eukaryotic heterochromatin and uncover unique heterochromatic systems. While exploring heterochromatin in species across the eukaryotic tree of life is key, most lineages have not been investigated due to complications with chromatin isolation, culturing, and genetic manipulation. To address these fundamental biological questions and overcome technical barriers, I will use a recently developed mass spectrometry method to identify proteins associated with known heterochromatic modifications in 19 species cultured in the Sebé-Pedrós laboratory representing all major and several early-branching eukaryotic lineages. To overcome genetic manipulation limitations, I will create a synthetic platform to heterologously assess reader-repressor functions of proteins in budding yeast. I will use this system to functionally characterize new regulators of heterochromatin from diverse eukaryotes. Finally, I will integrate these and other genomic data in a comparative framework to reconstruct the ancestral composition and evolutionary diversification of eukaryotic heterochromatin. Overall, my project will comprehensively identify the functional conservation and diversity of eukaryotic heterochromatin and create a powerful genetic tool to further explore chromatin function and evolution.

Mots clés : chromatin, evolution

Participants :
- Centro de Regulación Genómica (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €
Projet QC-SQUARED (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Quantum computing has the potential to provide an exponential speedup compared to classical computers, but the practical implementation is still in its infancy. Two central questions are: (1) in which field the current noisy intermediate-scale quantum (NISQ) hardware can provide benefits compared to classical computers and (2) which methods and algorithms enable this advantage? The aim of this project is to answer these questions by enabling accurate and efficient Quantum Chemistry calculations on current and near-term Quantum Computers for relevant chemical and physical problems. This paves the road to simulate strongly correlated electron systems of high scientific and economical interest, where accurate approaches are needed to understand groundbreaking chemical and physical phenomena, like high-temperature superconductivity, photosynthesis or nitrogen fixation. It will be achieved by developing and implementing novel quantum algorithms based on the combination of the transcorrelated (TC) method and a complete active space self-consistent field (CASSCF) embedding approach. The TC method will reduce the necessary quantum resources by providing accurate results for a small strongly correlated region already with small basis sets. While CASSCF will allow to target more realistic systems by embedding the correlated region self-consistently in a larger environment, which is efficiently described by inexpensive mean-field approaches. This project has the potential to go beyond the state-of-the-art by: (a) pushing the boundaries of currently possible quantum chemical calculations, allowing further theoretical understanding and practical design of quantum materials and (b) pave the road toward scientific and economical relevance of quantum computing already in the NISQ era.


Participants :
- IBM Research - Zurich (Suisse) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €
- École polytechnique Chalmers (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 222727.68 €
Projet AutoLLMSelect (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Large Language Models (LLMs) are gradually becoming part of academic and industrial processes due to their inherent capacity to solve a multitude of different problems across different domains. However, an open question remains – from the multitude of LLMs available, how to select the most appropriate LLM to use on a specific supervised machine learning (ML) problem (with or without fine-tuning), without evaluating a large portfolio of LLMs on the labelled dataset related to that ML problem. Evaluating a large LLM portfolio across multiple criteria introduces high computational cost, which then translates into a negative environmental impact, especially in terms of increased carbon emission. This proposal aims to (1) publish a comprehensive LLM benchmark dataset analysis that would facilitate a robust and unbised LLM benchmarking, (2) make the first steps towards a robust, explainable and evolving framework for automated LLM selection based on a multi-disciplinary approach that would reduce the cost for comparing large LLM portfolio on ML datasets, and (3) evaluate the applicability of the framework on a use-case from in field of sustainable development. Due to the high complexity of the problem to be solved, the proposal will present a proof-of-concept on a selected LLM portfolio, dataset portfolio, and performance metrics, based on the available data in public benchmarks. The framework would evolve and could be extended in the future with new LLMs, benchmark datasets, ML tasks, performance metrics, from both our side and the community.

Mots clés : deep learning, statistical data analysis, meta learning, representation learning, large language model

Participants :
- Université de Fribourg-en-Brisgau (Allemagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Institut Jožef Stefan (Slovénie) — Coordinator, beneficiary, Recherche, subvention : 182717.52 €
Projet ChemProFlav (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protease inhibitors can potently block the viral replication cycle. In the context of flaviviruses, NS2B-NS3 protease is a promising viral drug target because of its well conserved backbone among flaviviral species, opening the perspective of developing pan-anti-flaviviral NS2B-NS3 inhibitors. All reported NS2B-NS3 inhibitors, however, suffer from low potency and/or poor biopharmaceutical properties. Structural optimization has proven to be slow and challenging, in part because synthetic methodology for fast, chemically versatile and diversity-oriented modification is lacking. To address these challenges, we propose a methodology to assemble protease inhibitors with varying warheads and side chains in just 2 steps from common starting materials, and apply it to the discovery of pan-anti-flaviviral compounds. First, selected amide/carbamate and aldehyde building blocks will be condensed in a reported three-component reaction with phenylsulfinic acid and benzotriazole, delivering individual ‘masked’ N-acylimines. These will be further submitted to innovative cross-coupling steps, in which warheads will be introduced. Once the methodology is optimized and the scope is determined, at least 10 additional analogues of a known NS2B-NS3 inhibitor will be prepared with variations in the warhead, P1 side chain and P2-P3 moieties will be synthesized. They will be subjected to enzymatic affinity determination, binding kinetics analysis and cellular assays. Experimental data will be used to validate a Molecular Dynamics study of NS2B-NS3 inhibitors. The project is envisaged to deliver significant societal, scientific R&I, and economic impacts by managing flavivirus infections and creating business cases for industrial R&I in Europe.

Mots clés : flaviviruses protease inhibitors ns2b ns3 protease inhibitors pan anti flavivirals masked n acylimines palladium catalysis

Participants :
- KU Leuven (Belgique) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université d'Anvers (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175920.0 €
Projet SEABORD (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

SEABORD will explore the frontier fortresses of Eastern Mediterranean in a comparative perspective in order to assign their role in defence, socio-economic development and geo-political considerations during the Ottoman rule. This research will focus on fortress-towns of Peloponnese, Cyprus and Crete, considering their similar historical trajectory in establishing Ottoman sea borders in the Eastern Mediterranean. This project will be based on a research conducted and collected qualitative data in various archives (in Istanbul, Athens, London, Vienna and Nantes), and on other primary sources, and on-site fieldwork facilitated by advanced digital tools and methods. Combining use of unpublished archival material with development of new digital reproductions (3D images, GIS based maps), this research offers an innovative approach to share and engage with cultural heritage in Europe. Main outcomes of this project will be a monograph, conference papers (will be published in edited collective volumes or as journal articles), and a digital museum, which will contribute to disseminate the project results in a wider audience. During two years period of the MSCA European Fellowship (EP), the researcher will base her research and training activities at Science and Technology in Archaeology and Culture Research Center (STARC), at the Cyprus Institute (Cyl). As part of her fellowship, she intends to complete a 3-month secondment at the Department of History and Archaeology, at the University of Crete, to enhance her training and expand her research. Overall, this project aims address a significant societal challenge, primarily resulting from derision of systematic research on such monuments during the Ottoman rule in Greece, and elsewhere in Europe in general. Thus, dissemination, communication and outreach activities are designed fulfilling this aim promoting research on fortresses and castles, and other examples of built military heritage of the Ottoman past in Europe.

Mots clés : sea borders, fortresses, port towns, eastern mediterranean, ottoman empire, peloponnese, crete, cyprus

Participants :
- Université de Crète (Grèce) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Bureau de contrôle et de gestion de la recherche et de l'innovation ( Cyprus Institute) (Chypre) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 164328.0 €
Projet Water Governance (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The international peace and security architecture is undergoing urgent change to accommodate a conflict environment that will be increasingly shaped by the quality of environmental governance in a context of climate change. Water problems – with its associated drought, wild fires and flooding – are at the centre of changing conflict dynamics. The 2021 Report of the Independent Panel on Climate Change (IPCC) devoted 200 pages to this issue alone, highlighting the vulnerability of weak states and agricultural communities within them to water conflict stemming from poor regulation of access to scarce resources. In addition to a rise in water conflict, peace and security policy and practice is also adjusting to a global context of rapid technological, geo-political and normative change. Climate change and advances in techno-science are intricately linked in the UN’s Futuring Peace initiative, which explores the possibility of using big data, machine learning and social media to inform climate conflict prevention activities . The digital expansion of public space has also facilitated post-truth politics, which denotes the use of digital technologies by rising illiberal authoritarian and populist powers to question or fabricate scientific ‘facts’ about global issues, including both climate change and military conflict . Climate conflict narratives have placed peacebuilding practice between the objective truth claims of ‘big data’ and the ontological condition of ambiguity – or multitude of ‘truths’ regarding climate-conflict risk. This project will focus on how the inter-related issues of climate change, technology, rising illiberal global powers and post-truth politics cohere around water resources to influence conflict dynamics and the norms that underpin international peace and security intervention. It will involve a qualitative case study of international intervention, water governance and water conflict in the Ferghana Valley in Central Asia.

Mots clés : climate conflict ethnic violence environmental peacebuilding digital tools for peace water governance digital network society misinformation and disinformation

Participants :
- Université d'Uppsala (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 222727.68 €
Projet ECONOMICS (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

microRNA-34a (miR-34a) is mis-regulated in ~75% of cancers and is considered a promising drug target. In a recent clinical trial, miR-34a was used against terminal liver cancer showing promising result with remission of 3 patients. However, mortality remained high and was attributed to its ability to target multiple mRNAs. Project ECONOMICS will investigate this issue by elucidating the underlying structure and dynamics of multiple miR-34a:mRNA complexes using NMR spectroscopy and molecular dynamic simulations. This will provide information about the conformation of miR-34a which is mRNA specific. This can further be stabilized by mutations to increase target specificity of miR-34a leading to an improvement in clinical trial results. miR-34a targets and binds the 3’-untranslated-region (3’-UTR) of ~100 mRNAs via the RNA-induced silencing complex, resulting in downregulation of the associated genes. Recently, it was discovered that miR-34a attains a high energy excited state (ES) conformation for mRNA encoding gene SIRT1. Stabilizing this ES resulted in a two-fold increase in gene repression. Can miR-34a have a similar ES for other genes implicated in various cancers? This will be studied by exploring the structure and dynamics of miR-34a when complexed with 3’-UTR of the mRNA encoding the genes HNF4a, NOTCH1, NOTCH2, DLL1 and WNT1. Cellular environment is proposed to affect the ES of miR-34a, therefore a detailed conformational landscape of miR-34a:mRNA complexes will be mapped by comparing both in vitro and in live human cells (cancerous and non-cancerous). This study will provide targeting rules for microRNA within the cell and insight into its regulatory mechanism. This information will improve the efficiency RNA based drug development, giving a competitive edge to EU’s pharmaceutical industry, and ultimately realizing “Europe’s Beating Cancer plan” to achieve long-term survival of 70% patients with cancer by 2035.

Mots clés : in cell nmr spectroscopy, microrna 34a, molecular dynamic simulations, rna rna interaction

Participants :
- Université d'Uppsala (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172406.4 €
Projet InGATE (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The ability of neuronal networks to process and store information relies on the activity of diverse subclasses of inhibitory interneurons (INs). While the importance of inhibition in controlling key features of network function is being increasingly appreciated, the understanding of the role of INs in neuronal networks function is limited by the incomplete knowledge of the connectivity between the different IN subclasses and pyramidal cells. Such gap of knowledge is even more evident when considering the connectivity between INs and engram cells, i.e. subgroups of pyramidal neurons encoding specific memories. In this conceptual framework, the InGATE project will analyze specific amygdalo-hippocampal circuits involved in valence coding, where memories of stimuli imbued with negative or positive valence segregate in different engram cells in the BLA. InGATE will test the hypothesis that two broad INs subclasses, the parvalbumin (PV) and somatostatin (SST) expressing INs, differentially gate aversive or rewarding information from the BLA to the CA1 region of the ventral hippocampus. To this end, I will analyze the functional connectivity between BLA aversive or rewarding engram cells (formed during fear or reward conditioning) to pyramidal cells and PV/SST interneurons in vCA1. In parallel, I will study vCA3 Schaffer collaterals converging on those vCA1 pyramidal cells and PV/SST interneurons that receive inputs from the BLA aversive or rewarding engram cells. Thus, the ultimate goal of InGATE is to clarify how PV or SST interneurons shape engram cells in vCA1 by integrating valence-related information from BLA and multisensory contextual information from the vCA3 area. InGATE will combine several state-of-the-art methodological approaches to generate, identify and manipulate aversive or rewarding BLA engrams and isolate their targets in vCA1. In addition, it will exploit an in vivo approach to measure population activity of excitatory and inhibitory neurons in vCA1.

Mots clés : gabaergic inhibition, inhibitory engrams, egrasp, ventral hippocampus, associative memory

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 188590.08 €
Projet PhotoSurf (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

On surface synthesis is an emerging field that aims to adapt traditional organic chemistry reactions to the fabrication of atomically precise low-dimensional nanostructures. This has been made possible thanks to the catalytic properties of surfaces and their 2D confinement. Despite the rapid development of this field, there are still key fundamental aspects that require additional efforts. One of the main problems is the strong interaction of nanostructures with the catalytic metal surface that results in a real impeachment for applications due to the difficulty of decoupling the nanostructures from the surface. To solve this, the community, and the host group, have turned its attention to the use of photoreactions on an insulator for the formation of these nanostructures and low-dimensional materials without the use of thermal catalyzed processes on a metal surface.  The scientific objective of this fellowship is to develop computational tools to rationalize, and finally predict, possible photochemical reaction pathways of organic molecules deposited on surfaces. In particular we have three main objectives: create a virtual screening method for the study of molecular self-assembly on surface; study the effect of surface, substituent and self-assembly in the absorption spectrum of the molecule and a computational study of the photo reaction that can takes places on the surface. For these objectives we will take advantage of the computational tools developed during the phD and postdoc of the applicant for others fields, like biochemistry and wet chemistry, and apply them and develop new ones for the field of on-surface photochemistry together with the host-group . This synergistic approach, together with the experience and facilities of the host and collaborators, will lead to the successful completion of the project and to the strengthening the career development of the Researcher.

Mots clés : on surface catalysis, photoreaction, self assembly, dft, qm mm

Participants :
- Conseil supérieur de la recherche scientifique (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €