Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Orbital Cinema (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Graz — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1914274.0 €

Directly watching in slow-motion videos how electrons move in quantum mechanical orbitals and how this motion shapes the functionalities of condensed matter has been a dream shared by all natural and life sciences. Yet, this vision comes with the daunting challenge of mapping the microscopic structure of electronic orbitals with simultaneous ultrafast time resolution. We will turn orbital cinematography into reality. This seminal breakthrough will rely on the unique synergies between photoemission orbital tomography (POT), ultrafast photoelectron spectroscopy, lightwave electronics and advanced theory, developed and pioneered by us. Secured by our recent proof-of-principle studies, we will combine these aspects to transform POT to a cinematography at unprecedented time scales, faster than a single oscillation period of light. This will allow us to systematically explore the nanocosmos on its intrinsic femto- to attosecond (the billionth part of a billionth of a second) scales. We will take actual slow-motion movies of molecular orbitals during charge transfer processes, surface chemical reactions, and wave packet motion driven by lightwaves. Orbital Cinema will thus resolve key questions related to a wide range of applications, from next-generation optoelectronics, energy conversion, photochemistry and catalysis to prospective electronics at optical clock rates. We expect it to revolutionize our understanding of the nanocosmos by elucidating–on elementary spatio-temporal scales–the inner structure of quantum leaps, strong-field control of electrons, charge transfer processes, and chemical reactions as well as their control by electric fields and light. Since the dawn of quantum mechanics, the temporal evolution of electronic orbitals has been among the most sought-after, yet elusive quantum processes. Our model-free observation of orbital motion establishes an unprecedented ultrafast wave function lab that will carry us to the very foundations of quantum science.

Mots-clés : photoemission orbital tomography,ultrafast photoemission,lightwave electronics,time dependent density functional theory,charge transfer,chemical reactions,nuclear motion,wave packet dynamics
Projet ERC : GRAIL (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université de Groningue — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3595455.0 €

Without biological membranes, there would be no life as we know it. Lipid bilayers shield cellular content from the environment, creating defined micro environments with specific functionality. Transport of molecules and information across these membranes is carried out by integral membrane protein channels, receptors, pumps and transporters. Living cells maintain chemical gradients and electrical potential differences across their membranes, the potential energy of which can be accessed by the membrane proteins to perform useful work. Indeed, central processes such as metabolic energy generation and nerve impulse propagation directly depend on these membrane gradients. Due to their core role in the life of cells and in the health of living organisms, such proteins represent the majority of all current drug targets. Therefore, membrane proteins have been the focus of intense efforts to obtain high-resolution macromolecular structure information. However, the current lack of experimental methods to carry out time-resolved structural studies of membrane proteins at physiological temperatures and under physiological gradients leaves a gigantic blind spot is our mechanistic understanding. We will address this challenge by bringing together our complementary expertise in membrane protein biology, time-resolved structural studies, photochemistry and nano fabrication methods. We will link a set of state-of-the-art technologies to build a technology platform, based on a partitioned microfluidic liquid sample environment, optimised for high-resolution, time-resolved, structural studies of membrane proteins by serial electron diffraction from 2D crystals at room temperature and in the presence of physiologically meaningful membrane gradients for the first time. This will allow us to structurally validate models based on biochemical and computational data, and uncover new possibilities for modulation of function by small molecule therapeutics based on allosteric regulation.

Mots-clés : time resolved structural biology,membrane protein transporter mechanism,time resolved electron diffraction,liquid cell nanodevices,photoactivateable molecular systems
Projet ERC : MAGNESIS (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Madrid Institute for Advanced Studies — Pays : Espagne — Rôle : PI
Acronyme de l'entité : IMDEA
Type d'entité : Recherche
Financement ERC de l'entité : 3418750.0 €

In the last years, electrochemistry and electrocatalysis are increasing their impact across several fields. A major driving force comes from the promise of substituting current fossil-fuel powered thermal methods in the industry by electrochemical alternatives, driven by renewable electricity. However, electrochemical methods are still far from reaching the desired target performance. In this landscape, the recent discovery of magnetic fields enhancing electrocatalytic processes offers a plausible new strategy. The idea of boosting an electrocatalytic reaction by an external magnetic field becomes highly persuasive. Still, the origin of this phenomenon is hardly understood, given its complexity: dealing with a magnetic field, in an electric field, on a dynamic surface, during a chemical reaction is a multiple-body problem.  Our objective is to foster magneto-electrocatalysis by exploring rigorously the interplay between magnetic fields and electrocatalytic performance from atomic resolution in model systems up to full cell devices. This can only be achieved by a synergetic effort between experts in catalysis, surface science, magnetism and theory. We will focus on two relevant reactions: the spin-restricted water oxidation and the carbon dioxide reduction, both potentially spin-sensitive. Our aim is to validate the structural, electronic and magnetic key descriptors controlling this phenomenon, assessed by complementary ex-situ and operando data within the corresponding theoretical framework. Computational tools will consolidate the understanding and quantify the different mechanistic contributions to microscopic and macroscopic observations. The ambition with MAGNESIS is to define, in a rigorous way, the first principles and ultimate possibilities of magnetic fields in the development of advanced electrocatalytic methods, pioneering the novel field of magneto-electrochemical science & technology.

Mots-clés : magnetoelectrocatalysis,electrocatalysis,dft calculations,microscopy,multiscale modelling,magnetism,water electrolysis,water splitting,co2 utilisation
Projet ERC : CARAMEL (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Université de Marbourg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2476735.0 €

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 : NeuroSonoGene (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : CO-PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 4949998.75 €

Brain-machine interfaces are classically based on multi-electrode arrays. Optogenetics has revolutionized this ability to control neuronal activity through ectopic opsin expression but its application to large brains remains limited because of tissue light absorption and scattering. Ultrasound waves have been proposed for remote neuromodulation, but this approach has remained restricted to low-frequency excitation, to prevent brain tissue overheating, at the expense of spatial resolution. The expression of mechanosensitive proteins in neurons has recently made it possible to achieve the ultrasound (US) activation of neurons at high US frequencies, an approach named “sonogenetic”. Using the MscL mechanosensitive ionic channel, we recently provided a first proof of concept in rodents that cortical neurons can be activated in vivo by ultrasounds at a high spatiotemporal resolution and low intensity. Here, we propose to develop an integrated sonogenetic strategy for distant activation/inhibition of neuronal networks by ultrasound waves in large primate brains. The project includes: 1) optimizing and diversifying the sonogenetics actuators for safe neuronal control 2) designing technologies for patterned ultrasound stimulations, 3) demonstrating efficacy and high spatiotemporal resolution of the sonogenetic approach in controlling the primate visual cortex. This project is based on a unique synergistic combination of expertise, with a synthetic biologist in ion channel engineering, a neurobiologist with expertise in vision, and a physicist with expertise in ultrasound technologies. These 3 PIs will be supported by an expert in AAV vector mediated delivery. The project outcomes will be a novel brain-machine interface for investigating neural circuit function even deep within large brains through contactless sonogenetics. This sonogenetic technology will open new avenues for treating neurological dysfunction such as restoring vision in blind patients.

Mots-clés : neuroscience,neuromodulation,sonogenetics,ultrasound,brain machine interface,functional ultrasound imaging,vision,visual restoration,visual cortex
Projet ERC : DRIMMS (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université du Queensland — Pays : Australie — Rôle : PI
Acronyme de l'entité : UQ
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3367309.0 €

Successful defence against invaders is critical for survival of eukaryotic cells. Microbes have developed many strategies to subvert host organisms which, in turn, evolved several innate immune responses to counterattack. As major lipid storage organelles of eukaryotes, lipid droplets (LDs) are an attractive source of nutrients for invaders. Pathogens induce and physically interact with LDs and the current view is that they ‘hijack’ LDs to draw on substrates for host colonisation. We recently challenged this dogma by demonstrating that LDs are endowed with a regulated protein-mediated antibiotic activity. Our work intro-duced the new concept that dependence on host nutrients is a generic ‘Achilles’ heel’ of intracellular pathogens and LDs a chokepoint harnessed by innate immunity to organise a front-line defence.  Here, we have formed a multidisciplinary group combining complementary knowledge and transdiscipli-nary expertise to investigate the hypothesis that LDs are innate immunity hubs sensing infection and di-rectly confronting invaders. We will characterise, in cells and animals, how LDs efficiently coordinate and precisely execute a plethora of immune responses such as killing, signalling and inflammation. High-throughput proteomics and lipidomics will identify defensive players. 3D electron tomography and confo-cal microscopy will be combined with proximity labelling strategies and biochemical methods to get un-precedented understanding of host LD-pathogen dynamics. The successful pathogen Mycobacterium tuber-culosis will be used to test the medical significance of our findings and unravel bacterial mechanisms of resistance to LD-mediated defences.  Characterisation of these novel innate immune systems will be paradigm-shifting in immunology, physiol-ogy and cell biology. In the age of antimicrobial resistance and viral pandemics, unravelling how eukaryot-ic LDs fight and defeat dangerous microorganisms will inspire new anti-infective therapies.

Mots-clés : lipid droplets,bacteria,tuberculosis,lipids,mitochondria,cell biology,electron microscopy,proteomics
Projet ERC : GRAVITES (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université Louis-et-Maximilien de Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1332295.0 €

The four known interactions that occur in nature can be described either by Einstein's general relativity or by quantum field theory. Over the last decades physicists have tried to put these two pillars of modern physics on a common foundation. In doing so, they have been limited by a lack of experiments at the interface of these two frameworks. Both theories have been independently verified with astonishing precision, but all verifications to date have come without drawing on concepts from the other theory. The goal of GRAVITES is to perform experiments at the interface of quantum physics and general relativity. For the first time, we will measure gravitational properties of single and entangled photons in the background of Einstein’s gravity. To this end, GRAVITES aims to combine four complementary disciplines: quantum photonics and precision interferometry guided by expertise in general relativity and quantum field theory. The synergy among the research groups will realize a large-scale fiber interferometer with unprecedented precision. Since the sensitivity of GRAVITES’s apparatus must exceed present large-scale fiber-based quantum interferometers by orders of magnitude, the two experimental teams must combine cutting-edge technologies in their respective fields for advancing single-photon interferometry. These developments are also of direct relevance for many other applications such as quantum metrology and quantum sensing. In parallel, the theory teams will investigate the combined effects of gravitation and field quantization in dielectric waveguides. With this united effort GRAVITES is in the position to explore new physics that determines the gravitational properties of quantum superposition and quantum entanglement. This will allow us to create a unique experimental platform for probing how gravity interacts with the quantum world.

Mots-clés : quantum photonics,quantum gravity interface
Projet ERC : SHAPE (Horizon Europe, appel 2024, Synergy grants)
Entité participante : University of Missouri — Pays : Etats-Unis — Rôle : PI
Acronyme de l'entité : MIZZOU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1190190.0 €

We address a gap in research on the bi-directional effects of language on thought and thought on language, and the developmental pathways that transmit interactions between language and cognition from one generation to the next. The significant empirical advances we propose will result in a unified, cross-disciplinary theory which addresses language diversity through the dynamic interaction of language and cognitive systems across languages and cultures. To this end, we select shape as a core spatial property of entities in the physical world of things which determines bodily action on objects. The abstract properties of shape are codified in multiple ways in the world’s varied languages, including spoken and signed languages – in object and category labels and their organization into classes of categories, spatial prepositions, verbs, and quantifying expressions. Visual shape perception and shape representation in early perceptual and cognitive development are inherently intertwined and interdependent with early language acquisition. Children on atypical developmental trajectories show a cascade of disrupted development in both shape perception and language that can have substantial life-long consequences. Despite this compelling evidence of the pervasiveness of shape, no theoretical account has been offered to explain its nature as a system, neither has this topic been approached integrating evidence and methodologies across disciplines. The main goal of the current endeavor is to provide such an account from the point of view of systems theory and aligning methodologies across vision research, cognitive development, theory of language and language typology and sign language. Our premise is that shape holds a privileged status in human representational systems – in perceiving, using and reasoning about objects and in organizing the structures of the world’s languages and, as such, is key to understanding human intelligence and its developmental trajectories.

Mots-clés : shape perception and representation language development shape bias cross linguistic differences autism developmental language disorder
Projet ERC : TubulinCode (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2429721.25 €

Microtubules (MT) are core components of the eukaryotic cytoskeleton with essential roles in cell division, cell shape, intracellular transport, and motility. Despite their functional divergence, MTs have highly conserved structures made from almost identical molecular building blocks – tubulin proteins. A variety of posttranslational modifications (PTMs) diversifies these building blocks, which is thought to control most of the properties and functions of the MT cytoskeleton, a concept referred to as the ‘tubulin code’. While they appear to have subtle effects at the molecular level, tubulin PTMs are essential for maintaining cellular functions of MTs over large spatial and temporal scales. Yet, a comprehensive knowledge of the principles of the tubulin code, connecting its functions across the molecular, cellular and organismal levels, is almost entirely lacking. Our project aims to obtain a novel molecular and mechanistic understanding of how tubulin PTMs control long-term cellular function and homeostasis. Our unique approach bridges all relevant scales of biology and relies on a synergy between our powerful experimental models and expertise in biochemistry, structural biology, single-molecule assays, systems-biophysics, cell biology, and physiology. Specifically, we will: (1) Determine how different tubulin PTMs affect biophysical and structural properties of MTs and their interactions with associated proteins; (2) Define the impact of tubulin PTMs on overall MT cytoskeleton behaviour and the resulting physiological implications in neurons; (3) Combine zebrafish and mouse models and develop a novel fish model for lifelong in-vivo imaging to determine how the tubulin PTMs control lifelong MT-based functions. Our work will define the importance of tubulin PTMs by revealing their critical molecular functions over the lifetime of an organism. The project has the potential to substantially change our perception of the cytoskeleton’s role in homeostasis and disease.

Mots-clés : microtubule cytoskeleton,tubulin code,tubulin posttranslational modifications,axonal transport,neuronal homeostasis,zebrafish,mouse,danionella,in vivo imaging,motor proteins,in vitro reconstitution,cell mechanics
Projet ERC : DynaPLIX (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Lund — Pays : Suède — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3646723.0 €

Proteins are biological macromolecules that are vital to all processes of life. Understanding the functions of proteins has great scientific and commercial value: proteins are used as industrial enzymes, as pharmaceutical treatments, and many proteins are the targets of drugs. Current knowledge of protein function is primarily based on static structures, which have provided great insights about structure-function relationships that today form the basis for protein science and protein engineering. Proteins are, however, not static molecules, but undergo spontaneous transitions between alternative structural states, some of which are rare, transient conformations that are essentially invisible to traditional methods. These dynamical properties are known to be critically important for function, but high-resolution studies of dynamics have so far been conducted merely as an “add-on” following structural studies. To change the situation, we aim to establish “integrative biomolecular dynamics” by developing methods that integrate time-resolved X-ray crystallography, nuclear magnetic resonance spectroscopy, and molecular simulations to study the motions of proteins while they carry out their function. We focus on the challenging problem of molecular recognition because it represents a poorly understood frontier in molecular science where advances are expected to have great impact. Specifically, we will address the question of how proteins bind ligands by describing with atomic resolution the entire dynamic process to reach a consistent kinetic, thermodynamic, and structural view. We are at a point where it will be possible to develop the individual techniques required for our integrative biomolecular dynamics approach. As a team we can leverage ongoing developments in hardware and methods, while ensuring the tight integration between methods that is needed to study complex dynamical systems. We thus aim to move structural biology into a new era of protein dynamics.

Mots-clés : protein dynamics,ligand binding kinetics,molecular recognition,energy landscape,conformational ensembles,molecular dynamics simulations,time resolved x ray crystallography,nmr spectroscopy,nmr relaxation