Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : AMADEUS (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université Palacký — Pays : Rép. Tchèque — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3409401.0 €

The mantra ‘Automation + Miniaturization = Acceleration’ is successfully applied in many research areas and technologies, but not in synthetic chemistry, which is largely believed to be not automatable. However, with the potential to accelerate discoveries while flattening costs, increase safety, streamline data generation, enhance reproducibility, and lower the environmental footprint, automation and miniaturization are two promising approaches to synthesis and are worthwhile to invest in. I will engineer and validate a comprehensive, technology platform, AMADEUS (Automated, MiniAturizeD, and acceleratEd drUg diScovery), which is able to synthesize in a fully autonomous manner thousands of small molecules per day in nano- or picolitre volumes, based on hundreds of chemistries, efficiently screened and optimized for properties using artificial intelligence. The AMADEUS process will be achieved by interfacing four different modules: a synthetic part based on acoustic droplet ejection technology, coupled with a UPLC MS QC and purification module, and a flexible mounted screening unit. A machine learning module will retrieve and process all relevant synthesis, QC, and screening ‘real-time’ data and automatically guide the iterative optimization cycle. AMADEUS will be showcased with several medicinal chemistry, catalysis, and organic chemistry projects. With my project, I want to challenge the early drug discovery process, which for over 50 years in pharma companies around the world has (almost uniformly) been pursued and comprises two blocks, 1) a high throughput screen relying on millions of curated and stored compounds and 2) the subsequent hit-to-lead optimization phase often called the ‘design, make, test cycle’. AMADEUS will contribute to the accelerated discovery of drugs for unmet medical needs and ultimately reduce drug costs for patients. AMADEUS is a highly sustainable synthesis platform. AMADEUS will help democratize drug discovery.

Mots-clés : autonomous drug discovery technology platform nano synthesis miniaturized organic chemistry acoustic droplet ejection machine learning evolutionary algorithm redesign dmta accelerate early drug discovery chiral catalyst optimization personalized medicine p53 y220c covalent modifier rna targeting by small molecules immuno oncology pd l1 degrader
Projet ERC : 4D-SkINFLAM (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Leibniz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WLG
Type d'entité : Recherche
Financement ERC de l'entité : 2499188.0 €

To ‘feel comfortable in one’s own skin’ is an idiom referring to one’s confidence in interacting with others. However, when the skin is inflamed, as in atopic dermatitis or psoriasis, patients carry a sub-stantial burden leading to opposite effects. Current therapies target redundant, late-stage inflammatory events but not the disease drivers, leading to heterogeneous and insufficient efficacy. Understanding the proximal mechanisms of inflammation will stimulate the development of better therapies.  Among the innate immune sensors for stress and microbes in keratinocytes, mutations in the NLRP1 and NLRP10 inflammasomes are linked to skin disorders. These molecules and the pro- and anti-inflammatory IL-1 family members they regulate are differentially expressed in the different layers of the epidermis. We hypothesize that inflammasome signaling in keratinocytes needs context-dependent and spatio-temporal control to avoid inflammation, which poses unique analytical and conceptual challenges.  Therefore, to understand how inflammasome signaling in specific keratinocytes drives skin inflammation, 4D-SkINFLAM will i. optogenetically activate specific inflammasome components with spatio-temporal precision and perform a spatial analysis of transcriptomes and proteomes in neighboring cells. With loss-of-function approaches and pathway activity reporters, we will ii. define the ‘sensome’ and the activity of inflammasomes in different areas of the epidermis. Using mouse models, we will iii. evaluate how spatial inflammasome activity drives skin inflammation. Through iv. AI-driven deep visual proteomics combined with an analysis of inflammasome activity, we will discover spatial in-flammasome activation and its effects in inflammatory skin disorders. A precise understanding of spatio-temporal inflammasome signaling in the skin will be critical for se-lecting therapeutic targets acting as upstream drivers of prevalent diseases with high unmet needs.

Mots-clés : inflammasome,il 1 family,spatio temporal regulation,optogenetics,proteomics
Projet ERC : PINDESYM (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université nationale et capodistrienne d'Athènes — Pays : Grèce — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2395875.0 €

The automatic understanding of programs, in insightful, high-level terms, has long been a dream of computer science. The area of static program analysis has made significant progress in such understanding by algorithmically modeling all possible program behaviors. In this setting, declarative program analysis has recently demonstrated great success in capturing powerful algorithms efficiently and elegantly, in a form that bridges mathematical logic and intuitive human understanding.  The PI’s research has established a world-leading program in declarative program analysis, with multiple independent signs of high recognition. However, the dream of automatic deep program understanding remains elusive: static analysis tools are still reliant on significant human insights and extensive customization for the analysis domain. Is there hope for a giant step forward? The PINDESYM approach posits that two emerging breakthroughs offer excellent promise to take declarative program analysis to a next level, capable of realizing the dream of automatic program understanding. The first is the idea of combining a declarative system (e.g., a Datalog fixpoint engine) and a symbolic reasoning system, such as an SMT solver or algebraic rewrite system. The second is the seamless integration of a machine learning approach, over large amounts of data (from past code bases), in the declarative inference process.  The PINDESYM project will leverage symbolic reasoning and learning approaches to greatly advance program analysis. The challenge is dual: not only to invent powerful new techniques and algorithms, but also to capture all the diversity in symbolic, value-flow, and learning-based reasoning in a single, unified, reusable, and extensible analysis framework—a true deep program understanding engine, far beyond current approaches.

Mots-clés : program analysis
Projet ERC : Urban Frontiers (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : Université de Roskilde — Pays : Danemark — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 182173.5 €

No land, that government and developers see as future cities in the Global South, is vacant. There is no empty ‘no-man’s land.’ Individual citizens, social movements, squatters, and urban developers already engage in making their land use look legal. Urban property development in the Global South often starts out in illegality. Only subsequently does it become legal. This project explains how?  Mainstream research on the Global South sees urban land in technical terms of rapid urbanization, and the challenges of providing sufficient housing, infrastructure, and service. Yet, if we fail to understand the significance of institutional transformation of urban land, we will not understand the future political landscape in the Global South, as landed property is the pivot around which government and citizenship turn. With this project, I develop and combine two new concepts to explain how people - and not just the state - code access to land and then conjure up legality for facts already existing on the ground. Coding is rulemaking, whereas legalization gives a rule the quality of law. A rule’s quality as law is not intrinsic to the rule itself, but something attributed to it in social and political interaction. Governments make laws, but the originality of the present project lies in determining how multiple actors aim to make their land claims appear legal as if they were sanctioned and approved by state and law.  My team and I will collect material evidence (record artefacts from archives, material structures, physical markers and signs, boundaries, and documents and other expressions not produced directly for us) and ethnographic testimonies (from residents, land users, civil servants, lawyers, politicians, and developers) to establish how illegal land use is made to look legal.  Nine conflicts-case studies will be conducted in peri-urban areas of cities in Asia, Africa, and Latin America by 1 prof (PI), 3 assoc. profs, 3 postdocs and 3 PhDs.

Mots-clés : property,urban,frontier
Projet ERC : EuroFlash (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université d'Amsterdam — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1315067.5 €

Fast radio bursts (FRBs) present astronomers with a compelling mystery: what is creating these brilliant but ephemeral flashes that travel billions of lightyears before reaching Earth? Whatever is producing the FRBs, it requires an extreme energy density and the conditions for `laser-like’ coherent radio emission to be generated. While recent discoveries show that magnetars are a leading contender, the heterogeneous properties of the known FRB sample strongly suggest that there are multiple FRB source types. If so, then we have multiple mysterious FRB origins to uncover.  Due to the great interest in solving this puzzle, enormous progress has been made in recent years. There are now hundreds of known FRB sources, dozens of which repeat, and some of which have been localised to their exact galactic neighbourhoods. The FRB sample continues to grow at a rapid pace of several new sources per day, thanks to new wide-field radio telescopes. Studying these sources with dedicated follow-up is challenging because they emit sporadically and are only visible for milliseconds or less. At the same time, by casting an even wider net we are likely to discover new types of FRB-like signals. With EuroFlash, I will create a coordinated network of European radio telescopes operating over a broad range of radio frequencies, providing high sensitivity and observing cadence, and achieving the best-possible localisations. I will use this network to perform a world-leading, systematic study of repeating FRBs, to understand their progenitor(s) and their relation to the apparently one-off FRB sources. I will also make a novel exploration of the parameter space of short-duration radio transients by exploiting the large field-of-view of LOFAR2.0 and commensal observations to find new sources. In doing so, I aim to discover new types of astrophysical phenomena that probe the extremes of the Universe.

Mots-clés : fast radio bursts,radio astronomy,astrophysical transients
Projet ERC : DEEP CULTURE (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Université d'Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

In 2022, the world appeared transformed by a new consumer artificial intelligence (AI), which has dazzled observers with the ability to generate text, images or music. This transformation has been brought about not by general AI but by deep learning, a specific subset of machine learning that has come to dominate AI scientifically and commercially. This has given rise to an emergent ‘deep culture’, which is produced with universal data extraction and on an industrial scale. While these developments have led to much public anxiety, we lack an understanding of the fundamental shift in cultural relations through deep learning, and what this means for cultural production and analysis.  DEEP CULTURE is the first project to develop ‘deep culture’ as an object of study as well as a method and capacity to attend to this historical moment. It claims that the relations between culture and deep learning can be reconfigured if humanistic ideas are included, which address the complexities of culture and values of difference. To this end, the project advances a radical interdisciplinary framework at the intersection of digital humanities, cultural studies and computer science. DEEP CULTURE has three main objectives: i) to develop a critical inquiry about deep culture through epistemic translations of keywords and practices in deep learning; ii) to advance methodologies for a critical inquiry with deep culture by reconfiguring current deep learning techniques and practices through humanistic ideas and values; iii) to promote productive, critical relationships with and beyond deep culture by collectively contesting deep learning’s cultural enactments and co-producing new ones with diverse publics. Empirically, the project is situated at three archival sites: historical, real-time and incidental archives.  Based in Amsterdam, DEEP CULTURE is led by the first Distinguished University Professor in AI and Humanities and an expert on interdisciplinary research collaborations.

Mots-clés : digital humanities,cultural production,artificial intelligence,deep learning,archives,difference,ethico politics
Projet ERC : EvoInHi (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université d'Aarhus — Pays : Danemark — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 403571.0 €

The mammalian gut is an exquisite system to study ecology and evolution of microbes, and these processes are key for host-microbiome homeostasis. How microbiome diversity is maintained or lost is a critical question underlying the proper balance of this duet. Yet, our knowledge of the eco-evolutionary mechanisms structuring microbiomes is still in its infancy. Here, we seek to identify dominant modes of natural selection and host factors that modulate the evolution of their microbes. By leveraging knowledge on gene functions in specific strains and the power of mouse genetics and husbandry, we will unravel how natural selection operates to shape diversity in the bacteria that inhabit the guts of healthy and sick hosts. Microbiome evolution will be studied in several mouse models of disease with a focus on Escherichia coli as a pathobiont model, for which a deeper understanding of molecular mechanisms in health vs disease can be reached. Using long-term experimental evolution in vivo, high-throughput sequencing and theoretical modelling we will quantify the relative roles of directional, diversifying and fluctuating selection in gut evolution. We posit that resource competition drives the dominant selection mode in the healthy gut and that strong fluctuations in the environment, due to phage-bacteria co-evolution and/or due to hostmicrobe interactions, drive the selection mode in the gut of diseased hosts. We will further test the hypothesis that fluctuating selection leads to an Anna Karenina effect whereby the microbiomes of unhealthy individuals are much more distinct between one another than those of heathy ones. EvoInHi seeks to find the first empirical evidence that the predictability of evolution is higher in health than in disease, which will have a profound impact on understanding bacteria diversity and rates of specialization and how these can be used to modulate host health.

Mots-clés : natural selection,microbiome evolution,mouse models
Projet ERC : PhaseKin (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : German Center for Neurodegenerative Diseases — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DZNE
Type d'entité : Recherche
Financement ERC de l'entité : 2499943.0 €

Protein phosphorylation is a process that activates biological and cellular pathways. This process is carried out by enzymes called protein kinases that add phosphates to proteins. Protein kinases are crucial drug targets involved in the onset and progression of human diseases such as cancer and Alzheimer’s disease. Growing evidence suggests that protein kinases are regulated spatially and temporally by the phase separation and condensation of biomolecules into cellular organelles that are not surrounded by membranes. The molecular mechanisms that govern the action of kinases in phase-separated condensates, however, are unknown. Knowledge of these mechanisms is crucial for the development of better drugs that target protein kinases. To address this challenge, I have designed an interdisciplinary project that goes well beyond the state-of-the-art to explore in atomic detail the action of protein kinases intimately involved in Alzheimer’s disease and the abnormal phosphorylation of the protein Tau. The PhaseKin project aims to (i) reveal the specificity and reaction kinetics of protein kinases inside phase-separated condensates in vitro and in cells, (ii) decipher the dynamic conformational landscape of the protein kinases MARK2 and GSK3β by advanced NMR methods that will grant unprecedented detail on their modes of regulation, (iii) disentangle changes in population distributions and rates of interconversion between structurally distinct kinase states inside condensates, (iv) unravel the physicochemical basis of kinase drug partitioning into condensates. The highly innovative nature of the project is devised to delve into the heart of protein kinase function and to revolutionize our knowledge about the chemistry of drug-kinase interactions. Findings from the PhaseKin project will provide critical guidance in the development of more efficacious and specific drugs which target protein kinases.
Projet ERC : MEDAPP (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : University of Lleida — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : UdL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The Islamic conquest of Iberia in the 8th century brought in profound changes in the political, social and economic realms that transformed the everyday life of local rural and urban communities. Technological innovations and the arrival of new crops impacted their agriculture, diet and culinary practices. Plants were present in almost all aspects of medieval people’s ordinary lives (food, crafts, medicines, etc.). However, they have been commonly sidelined in discussions of the past. Most of what we know about plants in this multicultural period in Iberia is based on a limited number of archaeobotanical studies and on written sources, which despite their undeniable value they often reflect issues related to the elites. By contrast, archaeology, and more specifically archaeobotany and their associated science-based techniques, are placed in an extraordinary position for approaching issues related to plant production, processing, preparation and consumption, and how these connect to broader societal changes. By integrating archaeobotany and written sources, as well as applying ground-breaking techniques (plant genomics and food remains analyses), MEDAPP aims to disentangle what range of plants were used in Medieval Iberia (6th-11th CE); where new species came from and when were they introduced, who brought them, and how people engaged with them through different practices. The project sets a new holistic agenda for understanding the impact of the new political, economic and social system on agriculture, eating habits and culinary practices of Iberian medieval communities. This project aims at providing a step-change in the way agriculture, plant production, preparation and consumption have been studied in Medieval Iberia. It represents a golden opportunity to fill the voids of texts, looking for clues in the archaeobotanical record; an occasion to approach, with a suite of scientific and innovative methods, the unspoken information contained in these silences.

Mots-clés : archaeobotany,written sources,islamic,food,identity,storage,food remains,isotopes,genetics,
Projet ERC : VulnerableInhibition (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Helmholtz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HGF
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Septal GABAergic projection neurons are considered “pacemaker” cells as they enable the temporal organization of neuronal spike firing in hippocampal and entorhinal networks that support spatial- and object-coding. Accordingly, medial septum inactivation is associated with cognitive impairments, but the specific role of the septal-entorhinal GABAergic projections therein has remained unexplored. This is a pressing question, as we have evidence that septal GABAergic projections exhibit enhanced vulnerability. In mouse models with neurodegeneration, we found that septal GABAergic axons exhibit signs of degeneration when target cells in the entorhinal cortices are not yet impaired. Furthermore, we have evidence for mitochondrial pathology in the degenerating axons. These results prompt the following questions: How does malfunction of septal GABAergic projections translate into dysfunction of downstream networks involved in episodic memory and spatial navigation? What are the mechanisms that render septal GABAergic projections prone to vulnerability? Employing in vivo electrophysiology combined with optogenetics, behavioral studies, 2-photon imaging of axons and mitochondria in live mice and spatial transcriptomics, we will tackle the following issues: (A) assess how impaired septal GABAergic projections affect spatial- and object-coding in the medial and lateral entorhinal cortex (MEC and LEC), (B) assess the functional consequence thereof on spatial and associative memory in the LEC (C) gauge putative cellular mechanisms, with focus on mitochondria, that render septal long-range GABAergic projections vulnerable and (D) identify genes/gene networks whose expression is involved in degeneration of septal GABAergic neuron axons. With these studies we will elucidate how septal neurons contribute to cognition, reveal common mechanisms for axonal degeneration, and ideally identify novel biomarkers and therapeutic targets for “mitochondropathies”.

Mots-clés : mithocondria dynamics,axon degeneration,spatial coding,object coding,path integration,spatial transcriptomics