Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : NanoX (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Heidelberg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1770428.0 €

A driving force behind biomedical innovation lies in disease prevention, diagnosis and treatment. This requires a comprehensive understanding of how pathogens exploit living organisms across molecular, cellular, organismal, and population levels. Treatment of disease often relies upon interventions that restore the normal structure and function of cells. However, it is currently challenging to visualise and quantify detailed cellular changes within whole tissues in response to disease. Soft X-ray microscopy is a novel, exciting imaging modality which enables detailed structural and chemical imaging of whole cells without fixation or dyes. This technique is currently used to image cultured cells, but has yet to be applied to the examination of cells within the intricate 3D architecture of tissue with its complex cell-cell interactions. Imaging of diseased tissue in this way is crucial to gain meaningful insight into disease mechanisms, while remaining complementary to other imaging modalities and biological assays. Project NanoX aims to tackle this challenge, by merging the skillsets of a world-leading team with synergistic expertise in infectious disease, physics and structural biology to pioneer several innovations – (i) a targeted micro-biopsy tool for rapid tissue extraction for soft X-ray microscopy, (ii) high-throughput nano-resolution 3D imaging of tissues, (iii) novel integrative data mining approaches, and (iv) unprecedented insights into the pathogenesis of hepatitis E virus (HEV), an important emerging zoonotic viral infection with no specific therapies or vaccines, in healthy and immune-compromised individuals. The scientific and technological innovations that will be developed and deployed by NanoX will revolutionize clinical diagnostics and research by providing new ways to directly image, characterise, diagnose, and treat diseases in any species at a level of detail and complexity that was previously unattainable.

Mots-clés : soft x ray microscopy,tissue imaging,disease mechanisms
Projet ERC : DECOLeishRN (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2501241.0 €

Darwinian evolution plays a central yet poorly understood role in human disease. Iterations between genetic mutation and environmental selection drive cancer development, microbial infection and therapeutic failure, thus increasing human mortality. The molecular mechanisms that harness the deleterious effects of genome instability to generate beneficial phenotypes in these pathogenic systems are unknown. Here we investigate this important unsolved question in the protozoan parasite Leishmania that causes devastating human infections. In the absence of transcriptional regulation, these early-branching eukaryotes exploit genome instability to regulate expression by gene dosage. Leishmania thus represents an ideal system to investigate how genome instability drives fitness gain in fast evolving, eukaryotic cells, such as observed during cancer development. Synergizing our expertise in genomics, evolution, systems and RNA biology, we have recently made several breakthrough discoveries that link parasite fitness gain to epistatic interactions between co-amplifying genes of small, non-coding RNAs, which program epitranscriptomic and translational regulation. We hypothesize that these genome/RNome interactions generate the phenotypic landscape underlying Leishmania fitness gain. Our proposal investigates this ground-breaking concept through two Specific Aims that (i) combine experimental parasite differentiation and evolution in vitro and in vivo to reveal molecular mechanisms underlying Leishmania predictive adaptation and fitness gain, and (ii) investigate how RNA modification and non-coding RNAs contribute to adaptation by regulating mRNA stability and translational control. Our findings will be highly relevant to other fast growing, eukaryotic systems that rely on genome instability, such as cancer or fungal pathogens.

Mots-clés : eukaryotic fitness gain,genome instability,leishmania,non coding rna,post transcriptional control,translational regulation
Projet ERC : CARAMEL (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Université de Saint-Jacques-de-Compostelle — Pays : Espagne — Rôle : CO-PI
Acronyme de l'entité : USC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496205.0 €

Finding new synthetic compounds that facilitate membrane transport of impermeable bioactive molecules constitutes one of the grand scientific challenges in chemistry, biology, and medicine. Until today, the design principles of artificial transporters have been mainly restricted to membrane-targeting molecules with segregated hydrophilic and hydrophobic domains. We propose a disruptive strategy that uses boron clusters as membrane carriers that abandon the classical amphiphilic topology and exploit the (super)chaotropicity of boron cluster anions. Chaotropicity, historically associated with the salting-in effects of ions on proteins, has only recently been related to the affinity of large cluster ions to hydrophobic surfaces. In comparison to amphiphilic carriers, boron clusters are fully inorganic, highly water-soluble, globular in shape, and induce direct membrane transport despite being anionic in nature. The mere existence of these carriers defies all previous conceptual assumptions and biomimetic design criteria. Here, we introduce a new scenario for chaotropic membrane transport. A new chaotropic strategy will be introduced. A systematic transport screening will be carried out to study the fundamental physicochemical parameters and to generate a cargo-dependent predictive model for covalent chaotropic transport. Functional biomolecular hybrids will be validated to achieve proof-of-principle for the therapeutic potential. This proposal is aimed to fully unfold the potential of the new chaotropic scenario and intended to shake the very foundations of research in membrane transport.

Mots-clés : lipid bilayer,membrane transport,synthetic membrane carriers,peptide chemistry,counterion activation,boron clusters,intermolecular interactions,boron clusters,chaotropic materials,extracellular vesicles,protein delivery
Projet ERC : Green2Ice (Horizon Europe, appel 2022, Synergy grants)
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 : 2450421.0 €

Green2Ice will investigate the deepest and oldest ice and basal sediments drilled from the Greenland Ice Sheet (GrIS). Ice cores have been drilled the last 55 years, but the deepest ice containing basal materials has been preserved until now, and still holds undeciphered paleoclimatic messages. The breakthrough of Green2Ice is to develop and apply cutting edge dating methods on this unique sample collection and hence to reconstruct the age and the stability of the GrIS. A hypothesis to test is if the present GrIS formed at the time of the Mid Pleistocene Transition, 1,2 - 0.8 million years ago. One innovation of Green2Ice is to gain paleo-information of the past size of the GrIS to constrain future tipping points. This knowledge will reduce the uncertainty on estimates of future sea level rise. Green2Ice will bring together four PIs from three world leading institutions with complementary skills to lift this strongly interdisciplinary program. We will drill a replicate core at GRIP, to supplement the available material from five existing ice cores and ensure retrieval of sediments and rock material from beneath the GrIS summit. We will develop, improve and apply novel dating techniques (cosmogenic and radiogenic nuclides, OSL/IRSL, modeling of gas and isotope diffusion) to place constraints on past waxing and waning of the GrIS. State-of-the-art methodologies on fossil remains, organic matter, in situ produced and consumed greenhouse gases, and ancient bio-molecules will provide insights on the types of ecosystems and environmental conditions that emerged during ice-free conditions. Interpretation will include ice sheet modelling with data benchmarking to establish the climatic sensitivity of the GrIS. Earth system modelling and collaboration with the groups preparing the IPCC AR7 will bring the knowledge of the past into the future. The rare and unique basal ice and material can only be used once. This is the main high risk high gain component of Green2Ice.

Mots-clés : greenland ice sheet,mid pleistocene transition,ice free greenland,ecosystem,mass loss,sea level rise
Projet ERC : TACY (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université Eberhard Karl de Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3147836.0 €

Cyclacenes, i.e., cyclic versions of acenes consisting of linearly fused benzene rings, were first discussed in 1954 by Heilbronner, but - despite considerable synthetic efforts over decades - have remained an elusive class of compounds. Theoretical investigations suggest that cyclacenes are highly reactive due to pronounced polyradical character and significant ring strain. All prior attempts to synthesise cyclacenes failed, mainly because the final synthetic step of establishing a fully conjugated π-system was energetically prohibitive. Despite these challenges, cyclacenes remain intriguing synthetic targets because of their unique chemical, electronic, and structural properties as well as their potential applications in organic (opto-)electronics or spintronics. In this collaborative project, we will develop novel synthetic approaches, which synergistically combine efficient and high-yielding synthetic strategies of belt-type precursors that we will transform to cyclacenes by extrusion of suitable leaving groups under cryogenic matrix isolation conditions, on surfaces, in the solid state, and ultimately even in solution. Our synthetic approach is highly modular and allows to structurally vary the belt-type precursors, and thus the cyclacenes, by placing different substituents at the rims, including peri-annulation or isosteric substitution of CH units by heteroatoms. This research, combined with state-of-the-art computational investigations and characterization even on the single-molecule level, will provide unprecedented insight into the structure-property relationship of the fully conjugated zigzag topology present in cyclacenes and address fundamental questions of chemical reactivity and the interplay of aromaticity, strain and polyradical character. This knowledge will finally allow us to synthesise interlocked structures based on cyclacenes and to apply cyclacenes in controlled reactions on surfaces for creating further elusive materials such as polyacenes.

Mots-clés : polycyclic aromatic compounds,on surface synthesis,matrix isolation,nanobelts
Projet ERC : TRANSDIFFUSE (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université Purdue — Pays : Etats-Unis — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3651000.0 €

The quest for carbon-neutral aviation propels us toward uncharted technological frontiers. In TRANSDIFFUSE, we present an ambitious program to develop an AI-driven model that may revolutionize propulsion technologies. As a synergistic consortium, we unite the numerical modelling prowess of Valero’s team, the high-fidelity computational capabilities of Lehmkuhl’s group, and Paniagua's experimental ingenuity. TRANSDIFFUSE aims to develop new tools related to clean propulsion, specifically an AI-driven model called FluidGPT. In doing so, we expect to enable major advancements to the aeronautical and power generation sectors, including, for example, hydrogen pressure gain combustion (PGC) engines, which are compact, lightweight, high-efficiency turbines. In initiating FluidGPT, we aim to overcome challenges like those facing PGC, by exploiting the thing that has made compact turbomachinery so difficult to design: the troublesome transonic flows propelled from the combustor. With our model we aim to control and manipulate those transonic flows. Our approach to FluidGPT is anchored in characterizing, predicting, and then manipulating the intricate, unsteady, inherently difficult transonic flows—thus unlocking the design and development of transonic diffusing passages, a notorious obstacle to designing turbomachinery passages in new, compact, efficient engines. FluidGPT will model the Navier-Stokes equations for such conditions, enabling the prediction and control of previously unmanageable flow behaviours. A complete model of the Navier-Stokes equations in transonic diffusing passages has never been achieved by the scientific community, and our model will be able to reproduce flow configurations never seen before. Embracing innovation and synergy, TRANSDIFFUSE will also unlock new design guidelines and flow control techniques to surmount limitations across the aeronautical and power generation sectors. This program may redefine fluid dynamics modelling and control.

Mots-clés : navier stokes modelling,sensitivity analysis,flow control,measurement techniques,transonic turbomachinery
Projet ERC : LAST NEANDERTHALS (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université de Sienne — Pays : Italie — Rôle : PI
Acronyme de l'entité : UniSi
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3746132.5 €

Our closest relatives, the Neanderthals, abruptly disappeared 40 thousand years ago (ka) after having endured for 350 thousand years in a territory ranging from the Iberian Peninsula to southern Siberia. Decades-long research attempted to address the cultural aspects and the demographic and environmental factors that triggered their demise. Yet, there are no widely accepted scenarios that satisfactorily explain the extinction of the Neanderthal. These shortcomings are in part because the data available originated from a limited number of sites mainly in western and central Europe, which we now know were peripheral to the range of the last Neanderthals. To compellingly reconstruct the chain of events that led to Neanderthal’s extinction, the scientific community needs new extensive archaeological data, possibly from the core regions of the last Neanderthals’ range. Areas of western and central Asia and eastern and southeastern Europe were at the core of this range, served as gateways to marginal areas, and witnessed Neanderthals’ bio-cultural interactions with Sapiens and Denisovans. For the first time, three PIs with vast expertise on Neanderthals’ culture, biology, and paleoenvironments will synergistically attempt to bridge the knowledge gap between the core and the periphery of their range at the time of their decline between 60-40ka. Project LAST NEANDERTHALS will 1) accurately collect, date, integrate, and model new high-resolution cultural, bio-genetic, and environmental data from understudied areas in western and central Asia and eastern and southeastern Europe; 2) provide an unprecedented perspective on the last Neanderthals’ population dynamics; 3) offer a comprehensive and compelling explanation of the mechanisms that led to their extinction by integrating data from their entire range and formulating and testing nuanced hypotheses using new models and simulations; 4) serve as a proxy for the fate shared by all archaic human groups.

Mots-clés : middle paleolithic,early upper paleolithic,homo sapiens,ancient dna,neanderthal,western and central asia,eastern and southeastern europe
Projet ERC : MechVivo (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université technique de Graz — Pays : Autriche — Rôle : PI
Acronyme de l'entité : TU Graz
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 4149582.5 €

Computational biomechanics is a fast-growing area of science. However, many of its fruits have not yet been translated into clinical practice. The main barrier to the translation of computational biomechanics into clinics is the lack of information about patient-specific mechanical properties of biological tissues. There are some methods for partially assessing these properties, but they have substantial limitations. A major cause of these limitations is the operating principle of current approaches, which rely on the analysis of the response of a tissue to some form of mechanical loading in vivo. To overcome this bottleneck, we propose a paradigm change. We will develop a method to infer mechanical properties of soft biological tissues in vivo based on a fundamentally new operating principle. To this end, we will leverage the synergy of three scientific areas covered by the three principal investigators of this project: (i) magnetic resonance imaging (MRI), (ii) experimental biomechanics, and (iii) physics-informed machine learning. Specifically, we will develop a new type of subvoxel MRI relaxometry to probe tissue microstructure non-invasively and establish a combined experimental and computational framework that will uncover for the first time the mechanistic link between transcriptomics, microstructure, and mechanical properties of soft biological tissues in a detailed manner. By leveraging this information with novel physics-informed machine learning techniques, we will gain the ability to determine the mechanical properties of soft tissues from clinical MRI data and blood samples with unprecedented accuracy and completeness. Our approach will be a crucial steppingstone to translate biomechanical computational models into clinical practice at a large scale. As a proof of concept, we will demonstrate how our new method can support the diagnosis of heart failure with preserved ejection fraction (HFpEF), one of the most common causes of mortality and morbidity.

Mots-clés : biomechanics,solid mechanics,materials modeling,soft tissue biomechanics
Projet ERC : MicroClock (Horizon Europe, appel 2024, Synergy grants)
Entité participante : John Innes Centre — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : JIC
Type d'entité : Recherche
Financement ERC de l'entité : 2830023.25 €

Circadian clocks are biological timekeepers. They structure processes - from molecular pathways to behavioural attributes - over the 24h day. They are pervasive in eukaryotes yet remain almost completely unknown in bacteria. We propose to address this major knowledge gap by capitalising on our recent breakthrough discovery of a circadian clock in Bacillus subtilis. Our unpublished data reveal that robustness of the B. subtilis circadian clock increases when co-cultured with either the plant Arabidopsis, or the yeast Saccharomyces cerevisiae. We propose that the mutualistic interactions between microbes and other organisms in their environment utilise circadian clocks, allowing us to propose the new concept of “temporal mutualism”. Within this project, we will identify and understand the molecular structure and function of the B. subtilis circadian clock (WP1), which will be the first detailed characterisation of a circadian clock in a non-photosynthetic bacterium. We will exploit the interactions that occur between B. subtilis and plant circadian clocks to define this new concept of temporal mutualism (WP2 and 3). Co-culture of B. subtilis with S. cerevisiae will identify regulatory nodes that are common to plant/bacterium and fungus/bacterium temporal mutualism (WP3). We will probe the novel hypothesis that biofilm enables intra-species temporal mutualism via differentiated cell populations within the matrix-bound structure (WP3). We will use circadian formalisms (behaviour), molecular systems analysis and state of the art technological approaches (e.g., combinations of microfluidics, microscopy, reporter gene technology and optogenetics), which is only possible through our interdisciplinary collaboration. This work will drive a paradigm shift, to open a completely new field that will change current thinking by bridging chronobiology with microbiology and ecology.

Mots-clés : circadian rhythm,circadian clock,chronobiology,bacillus subtilis,arabidopsis,saccharomyces cerevisiae
Projet ERC : REM@KE (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Pavie — Pays : Italie — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3857884.0 €

The fundamental objective of REM@KE is to reconstruct the sound and the function of lost musical instruments and to develop new theoretical, empirical, and practical tools to explore the embodied musical knowledge emerging from the relationships between these instruments and their performers. Among the great variety of objects of the past that inhabit museums, musical instruments are in a category of their own: if kept silent, music cannot be; if played, their materiality is endangered. These instruments are at risk of being silenced forever, as their conservation becomes the priority. To ensure access for future generations, a radical intervention is needed, to comprehensively study how they sounded and played when they were new, as well as their design principles and construction processes, so that they may be reconstructed, played, and heard both materially and virtually. To investigate the sound of these objects, we have developed a new research framework ‘Cognitive and Digital Organology’ (CaDO) that builds new bridges between organology, performance practice research, and cognitive sciences. CaDO will study the people involved with music, the instruments producing the sounds (interlocked into a system that evolves over time), in a space that is social, material, and digital. Embodied cognitive science will be used to examine how resources from the bodies of builders, players, educators, and listeners determine their musical experiences, fostering new relationships that are formed and transformed in acts of musicking. Thus, CaDO can inspire richer understandings of the experiences of those who engage with historical musical instruments and their replicas. By reinterrogating the relationship between instrument, gesture, and music REM@KE aims to reclaim the sound of historical instruments, improve our understandings of how we engage with them, and guarantee a better future for them.

Mots-clés : organology keyboard organ clavichord harpsichord pianoforte cognition restoration conservation virtual reality mixed reality