Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : IntraMAP (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université rhénane Frédéric-Guillaume de Bonn — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499241.0 €

Cellular behaviour is methodically studied using systems biology approaches that analyse the presence, absence, or oscillation of biomolecules. To this end, exogenous perturbations, among others, are used to alter protein expression and study their effects on cellular homeostasis. However, proteomes are inherently versatile and diversified by alternative splicing, protein cleavage, and post-translational modifications (PTM). Similarly, the spatiotemporal formation of multicomponent complexes plays an important but less well understood role in cellular homoeostasis and disorders. Specific recognition of these complexes by ligands is a difficult task to solve. Therefore, deciphering signalling cascades at the proteome and complex levels requires technologies that enable the identification of protein-binding and -inhibiting compounds that are sensitive or tolerant to PTMs and can recognize protein complexes. Intracellularly expressed aptamers, known as intramers, offer a solution to this challenge. The IntraMAP project will develop generally applicable paradigms for the automated evolution of intramers and combine them with cellular screening methods. In this way, intramers will be identified that are optimally adapted to cellular environments and effectively disrupt signalling cascades. These intramers will be used to identify signalling components and protein complexes associated with these cascades. They will be applied to various cells, organoids and in vivo to uncover fundamental principles of complex signalling events. The project has a strong interdisciplinary focus and will open novel avenues for the analysis of biomolecules. It has implications ranging from life sciences to systems biology, and will not only establish intramers as a broadly applicable discovery technology to study signalling cascades on an ‘omics’-like scale, but also holds enormous innovative potential for the development of novel gene therapies and future RNA-based drugs.

Mots-clés : aptamer,intramer,nucleic acids,synthetic biology,systems biology,cancer,signal transduction,fluorogenic rna,light up sensors,target identification
Projet ERC : OPEN BORDERS (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Znanstveno-raziskovalno sredisce koper — Pays : Slovénie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2474330.0 €

This project aims to rethink the history of Cold War Europe by examining the development of transnational cross-border cooperation from the end of World War II to the present. Overcoming traditional narratives of a clear-cut European separation symbolised by the Berlin Wall, a decentralised analysis of recent European history will show us that the question of a divided continent should be reframed. The final objective is to challenge a dichotomous vision of two separate Europes, “East” and “West”, from a new, border perspective. To this end, a highly qualified team of senior and junior scholars under my guidance will focus on the Alps-Adriatic region, a historical area that is now shared by Austria, Italy, Slovenia and Croatia. This case involves a relatively narrow geographical area but an unusually broad typological range of subjects. During the Cold War it was divided among socialist but non-aligned Yugoslavia, capitalist but neutral Austria, and NATO and EEC member Italy. Its development from the "southern end" of the Iron Curtain in 1946 to the "most open border" during the Cold War and a precursor to present-day Schengen Europe, represents a paradigmatic case to study an alternative attitude towards borders, frontiers and boundaries. Drawing on Cold War and borderland studies, social history and the history of European integration, which up till now have not found common ground, our innovative conceptual elaboration will demonstrate the interplay between top-down politics and bottom-up initiatives, thus offering a new, and more nuanced history of Cold War Europe from the border perspective. Reconsidering the European past from this transnational angle, both in terms of geographic and methodological perspectives, will allow us to rediscover the human face of European integration and will offer us a new platform for contemporary discussions on sovereignty, territoriality and belonging and on the future role of borders in Europe and in the world.
Projet ERC : ExtenDD (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université de Łódź — Pays : Pologne — Rôle : PI
Acronyme de l'entité : UŁ
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1629775.0 €

The project is concerned with two areas which so far have rarely come together: complex terms and proof theory. ExtenDD focuses on definite descriptions as the most important and troublesome singular terms and on sequent calculus and its generalizations as the most important tool of modern proof theory. Since Russell's 'On Denoting', regarded as a paradigm of analytic philosophy, definite descriptions occupy a central place in philosophical research and many deep and detailed studies have been carried out. The second half of the 20th century saw the development of new approaches to this phenomenon based on non-classical logics, in particular free logic in which, contrary to Frege's and Russell's classical logic, it is not assumed that every term refers. Yet despite the long history of research into definite descriptions, a paradigm of formal logic has so far rarely been applied to them: proof theory. The methods developed by Gentzen, in particular those relating to his sequent calculus, provide the means for the deepest study of proofs and their properties. Yet only a small effort has so far been put into the adequate treatment of definite descriptions in this framework. The same counts for other complex singular terms such as set abstracts and number operators. ExtenDD fills this important gap in research. Applying the methods of proof theory to definite descriptions is profitable to both sides. Competing theories of definite descriptions and complex terms in general, their advantages and shortcomings, are shown in a new light. The behaviour of complex terms needs subtle syntactical analysis and requires enriching the toolkit of proof theory. ExtenDD deals with both challenges: it develops formal theories of definite descriptions and modifies the machinery of proof theory to cover new areas of application. The realization of ExtenDD affects significantly the field of proof theory, automated deduction and philosophy of language.

Mots-clés : proof theory,definite descriptions,philosophy of language,non classical logic
Projet ERC : GOFIXIT (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université de Fribourg-en-Brisgau — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2963906.0 €

Biological nitrogen fixation is nature’s alternative to the industrial Haber-Bosch process that currently feeds at least half of the human world population through the provision of nitrogen fertilizers. In addition to its high energy demand, the process increasingly leads to various ecological problems, as its annual output steadily grows with demand. Haber-Bosch ammonia synthesis leads to the release of the greenhouse gases CO2 and N2O and to eutrophication of waters and aquifers because a substantial portion of nitrogen is lost to competing chemical and biological processes. One solution for this is to transfer the enzyme directly into food crops.  GOFIXIT will establish the recombinant production of a complete nitrogenase enzyme system in a heterologous host and make a link to central metabolism, effectively converting the host into a functional diazotroph. Nitrogenase is a two-component metalloenzyme that is uniquely able to reduce chemically inert, atmospheric N2 into its bioavailable form, ammonium. It occurs only in prokaryotes, is highly sensitive to O2, and it requires large amounts of metabolic energy in form of ATP and a strong reduct-ant for catalysis. To obtain a functional production system, all these points must be addressed in parallel. Based on our long record of research on nitrogenases, we are ideally positioned to succeed, focusing on our unique competence in preparative protein biochemistry and analysis. We have produced, isolated, and structurally characterized all three nitrogenase isoforms, and developed the spectroscopic and structural tools for a detailed analysis of their intricate metal cofactors. GOFIXIT focuses on the production of the enzyme components, and based on their analysis chooses, tunes, and applies the required accessory machineries for the synthesis, maturation, transfer, and insertion of the catalytic metal centres that are unique to this class of enzymes.

Mots-clés : biological nitrogen fixation,enzyme refactoring,anoxic protein biochemistry,metabolic engineering
Projet ERC : MultiMelt (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université de Twente — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Melting and dissolution induce temperature and concentration gradients in liquid systems. These gradients induce flows, namely buoyancy driven flows on large scales and phoretic flows on small scales. Such flows locally enhance or delay the melting or dissolution process and thus determine the objects’ shape. On large scales, a relevant example for the climate are glaciers and icebergs melting into the ocean, where cold and fresh meltwater experiences buoyant forces against the surrounding ocean water, leading to flow instabilities, thus shaping the ice and determining its melting rate. Another example is the dissolution of liquid CO2 in brine for CO2 sequestration. Next to buoyant forces also phoretic forces along the interfaces come into play. For dissolving drops at the microscale the phoretic forces become dominant. The resulting Marangoni flow not only affects their dissolution rate, but can also lead to their autochemotactic motion, deformation, or even splitting. In spite of the relevance for these and many other applications, such multicomponent, multiphase systems with melting or dissolution phase transitions are poorly understood, due to their complexity, multiway coupling, feedback mechanisms, memory effects & collective phenomena. The objective of this project is a true scientific breakthrough: We want to come to a quantitative understanding of melting & dissolution processes in multicomponent, multiphase systems, across all scales and on a fundamental level. To achieve this, we perform a number of key controlled experiments & numerical simulations for idealized setups on various length scales, inspired by above sketched problems, but allowing for a one-to-one comparison between experiments and numerics/theory. For the first time, we will perform local measurements of velocity, salt concentration, and temperature and connect them to global transport processes, to arrive at a fundamental understanding of such Stefan problems in multicomponent systems.

Mots-clés : turbulent thermal convection,double diffusive convection,taylor couette turbulence,melting,dissolution,marangoni force
Projet ERC : ANTI-ATHERO (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Ministry of Health — Pays : Espagne — Rôle : PI
Acronyme de l'entité : MISAN
Type d'entité : Recherche
Financement ERC de l'entité : 2495995.0 €

Cardiovascular disease remains the leading cause of mortality worldwide, with atherosclerosis (AT) as the primary underlying factor. Ageing is the strongest risk factor for both AT and CVD. Emerging evidence indicates that the B cell-mediated immune response plays a pivotal role in the development and progression of AT, although the nature of this response and its triggering antigens are poorly understood. In our prior research, we identified ALDH4A1 as novel AT antigen and showed that anti-ALDH4A1 A12 antibody is atheroprotective in mice. Our recent preliminary data show increased titers of anti-ALDH4A1 antibodies in aged mice as well as a rise in age-associated B cells in AT mice. These findings suggest a strong link between ageing, the B cell immune response, and AT. ANTI-ATHERO aims to functionally dissect the AT antibody response with the ultimate goal of identifying age-associated antigens that can serve as targets for specific immunotherapies. We will pursue the following aims: 1) characterize the early and aged B cell immune response in AT with time-stamping mouse models, 2) generate a single cell clonal atlas of time-stamped AT B cells and identify individual antibodies and antigens associated with the early and the aged AT antibody response, 3) translate our findings to human disease by mapping the B cell response in clinical AT and testing the identified antigens as markers of disease progression and, 4) evaluate the therapeutic potential of the identified antibodies and antigens through passive and active immunization strategies. We anticipate that the ANTI-ATHERO project will generate transformative insights into the interplay between ageing, the immune system, and AT. Our findings have the potential to significantly advance not only cardiovascular research but also contribute to a broader understanding of other age-related diseases and autoimmune disorders.

Mots-clés : antibody,germinal center,atherosclerosis
Projet ERC : UNATI (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université de Navarre — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498466.0 €

Europeans are the largest alcohol consumers. Policymakers and clinicians are currently perplexed on how to reduce alcohol harms in drinkers, due to contradictory guidelines: abstention is proposed as the healthiest option by many health advocates, stating that “there is no safe level of alcohol intake”; but most nonrandomized studies found lower all-cause mortality and other outcomes in moderate drinkers than in abstainers among subjects >50 years. However, potential biases may compromise these latter studies, particularly when effects are null or moderate. A large pragmatic randomized controlled trial (RCT) of realistic advice aimed to change behavior addressing clinical endpoints is long overdue. It will provide first-level evidence to confront the harms of one of the most widely used substances by humankind. Business issues and conflicts of interests are also at stake. We propose a 4-year non-inferiority RCT with >10,000 drinkers (men 50-70 years or women 55-70 years consuming >=3 but <40 drinks/wk). To reduce alcohol-associated harms they will be randomized in a 1:1 ratio to 2 advices: 1) abstention; 2) moderation (<=7 drinks/wk (females) and <=14 drinks/wk (males)), and avoidance of binge drinking, with preferential consumption of red wine with meals, and consumption spread out throughout the week. Moderate consumption is hypothesized to be non-inferior. No participant will be invited to increase his/her alcohol intake. The primary endpoint will be a global index of all-cause mortality, cardiovascular events, cancer, liver disease, depression, dementia, diabetes, tuberculosis or other major infection or injury. The difficulties for feasibility are significant, but more complex large behavioral trials developed by the principal investigator (PREDIMED and PREDIMED-Plus, two largest nutritional trials conducted in Europe) have attained sufficient compliance in changing not only one aspect of the dietary pattern (alcohol) but many aspects of diet and lifestyle.

Mots-clés : alcohol,dietary intervention,non inferiority pragmatic trials
Projet ERC : MORE (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 562477.5 €

This project is a contribution to moral philosophy, to the didactics of transformative reading and to medical ethics education. It examines moral residue (MR); the distress experience common among health care practitioners as well as other moral agents of recognizing what they take to be their own failure to meet a moral requirement, despite not being fully blameworthy for that failure; and which they express through regret or anguish. Our overall aim is threefold: (1) to substantially advance the philosophical and phenomenological understanding of MR, as a concept and as an experience, by analysing situations of MR caused by moral dilemmas, and by directing attention to situations that have not been explored or are under-explored - MR caused by unavoidable normative ignorance or by impermissible emotions; (2) to empirically study the impact of literary narrative fiction (that is thematically related to MR) in altering concepts of self and others, a process we call “transformative reading”, and (3) to devise, and to empirically test the potential merits of a novel narrative method for medical ethics education that we believe can enable health care practitioners to learn how to acknowledge their inherent vulnerability to MR, and to accept that they are likely to fail morally in ways that they may not be able to avoid, without this acceptance compromising their sense of dignity as moral agents. The aims are intimately connected in that it is the philosophical research into MR which motivates and enables the didactic part of the project, and which thereby binds it together into an integrated whole. The investigation is conducted in health care because this context makes apparent the full range of contingencies in life that impose limits to the rational exercise of moral agency, and which thereby lock agents into diversified situations of MR. However, since MR is pervasive also outside of health care, we believe it will benefit other branches of applied ethics as well.

Mots-clés : acceptance,aporia,dialogue,didactics,disease,catharsis,comedy,error,fallibility,fear,diminished agency,impermissible emotions,laughter,moral agency,moral conflict,moral dilemma,normative ignoranc,pity,ridicule,shame,taboos,tragedy,transformative reading
Projet ERC : RIPECROP (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université de Navarre — Pays : Espagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 88500.0 €

Cancer immunotherapy achieves unprecedented efficacy against a number of malignant diseases. Preclinical experiments in mouse models conclude that type-1 dendritic cells (cDC1) that present tumor antigens are an absolute requirement for most immunotherapy strategies to be efficacious, including those routinely applied to cancer patients at present. cDC1 cells are specialized in redirecting engulfed cell-associated antigens to the class I MHC antigen-presentation pathway in the context of IL-12 production and co-stimulation, at least when cDC1 cells are in the presence of moieties denoting viral infection. Such phenomena are key to prime anti-tumor T lymphocytes through a mechanism known as crosspriming. The RIPECROP project will test immunotherapy agents that enhance the numbers and performance of cDC1 in the tumor tissue microenvironment. The strategies will be based on mRNA constructs that will encode engineered forms of the cDC1 growth factor sFLT-3L, single-chain interleukin-12, cDC1 specific chemoattractants and bispecific costimulatory ligands targeted to surface proteins of cDC1 cells. The new therapeutic agents in the form of coding mRNAs will be expressed in vivo either intratumorally or using the mRNA-transferred liver as an internal “biofactory” to systemically produce the encoded proteins and their combinations. Innovative in-vivo screenings based on hydrodynamic gene transfer of the liver with various expression plasmids encoding heterodimerization systems will be performed to identify suitable new mRNA-based immunotherapeutic chimeric constructs to enhance antitumor T-cell crosspriming. Overall, a novel mRNA-based toolbox will be studied both in terms of anti-tumor efficacy and regarding the mechanisms of action, in such a manner, that crosspriming will become exploitable in combinatorial approaches for cancer immunotherapy.

Mots-clés : crosspriming,cancer immunotherapy,mrna,intratumoral,adoptive t cell therapy,viral mimetics,radiotherapy,synergistic immunotherapy combinations
Projet ERC : Supersolids (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Conseil national de la recherche — Pays : Italie — Rôle : Partner
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 131250.0 €

Supersolids are a paradoxical quantum phase of matter that combines the properties of superfluids and crystals, searched for long time in quantum solids and many other systems. Recently, we discovered a novel cluster phase in a quantum gas of magnetic atoms which realizes a supersolid. However, the limited size, the inhomogeneity, and the lack of appropriate detection methods have allowed so far to assess only very basic properties of supersolids. Here I propose an innovative density-phase microscope and original ideas that combine the best of matter-wave and condensed-matter methods to unveil the extraordinary properties of supersolids. With a two-layer superfluid-supersolid configuration we will measure both density and phase of the supersolid. With controllable optical potentials we will realize large, homogeneous crystal geometries in 1D and 2D. With high-resolution optical addressing we will manipulate locally the wavefunction, e. g. creating phase patterns or force fields, and we will follow the local dynamics. Our main goal is to explore fundamental properties that are largely unknown even theoretically: variable superfluid density under rotation; variable angular momentum of quantized vortices; dissipation-less deformation of the crystal; Josephson effect without barriers; quantum entanglement properties. We will also attempt the realization of new types of supersolid, to prove the generality of the phenomena: with coupled supersolid layers, we will move towards supersolidity in 3D; using a quasi-2D environment, we will attempt to realize two proposed types of strongly interacting and strongly correlated supersolids. Our work will establish connections between supersolids and other patterned quantum phases, such as pair-density waves in superconductors and in helium superfluids, intertwined phases in low-dimensional superfluids, and pasta phases in neutron stars. Our work might open directions for the realization of materials with novel functionalities.

Mots-clés : superfluids,quantum solids,quantum phase transitions