Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Active-DNA (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : National University of Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2349603.0 €

During the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab. The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.

Mots-clés : molecular programming,dna computation,dna nanotechnology
Projet ERC : BEAL (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Liège — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1837625.0 €

During the course of eukaryote evolution, photosynthesis was propagated from primary eukaryotic algae to non-photosynthetic organisms through multiple secondary endosymbiotic events. Collectively referred to as “secondary algae”, these photosynthetic organisms account for only 1-2% of the total global biomass, but produce a far larger part of the global annual fixation of carbon on Earth. ATP is the universal chemical energy carrier in living cells. In photosynthetic eukaryotes, it is produced by two major cellular processes: photosynthesis and respiration taking place in chloroplasts and mitochondria, respectively. Both processes support the production of biomass and govern gas (O2 and CO2) exchanges. On the other hand, anaerobic fermentative enzymes have also been identified in several primary and secondary algae. The regulation modes and interactions of respiration, photosynthesis and fermentation are fairly well understood in primary green algae. Conversely, the complex evolutionary history of secondary algae implies a great variety of original regulatory mechanisms that have been barely investigated to date. Over the last years my laboratory has developed and optimized a range of multidisciplinary approaches that now allow us, within the frame of the BEAL (BioEnergetics in microALgae) project, to (i) characterize and compare the photosynthetic regulation modes by biophysical approaches, (ii) use genetic and biochemical approaches to gain fundamental knowledge on aerobic respiration and anaerobic fermentative pathways, and (iii) investigate and compare interconnections between respiration, photosynthesis, and fermentation in organisms resulting from distinct evolutionary scenarios. On a long term, these developments will be instrumental to unravel bioenergetics constraints on growth in microalgae, a required knowledge to exploit the microalgal diversity in a biotechnological perspective, and to understand the complexity of the marine phytoplankton.

Mots-clés : endosymbiosis,algae,oxygenic photosynthesis,mitochondrial respiration,anaerobic fermentation
Projet ERC : DIVERSIPHAGY (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Ruhr University Bochum — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : RUB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1070774.5 €

During the course of evolution, plants have been exposed to a plethora of beneficial and pathogenic microbes. While symbionts are beneficial for the host plant by improving nutrient supply and health, pathogens are reprogramming their host only for their own benefit. At the interface of this interaction proteomes at both sides are highly flexible and require regulated protein turnover. In line with this, our previous work revealed that regulated protein degradation by autophagy is an essential player in plant immunity. Consequently, plant pathogens hijack autophagy during binary interactions though in contrasting manners. However, in a more complete scenario, plants are constantly exposed to different microbes and hence it is crucial to include the microbial diversity into this equation to obtain a holistic picture of the role of autophagy in plant-microbe interactions. The picture is getting even more complex if we look at the cellular diversity on the host side. Thus, DIVERSIPHAGY approaches the role of autophagy through bacterial and cellular diversity on the host side. We aim to address following questions: • Identifying how the bacterial diversity impacts autophagy and vice versa • Determining new bacteria and/or bacterial communities hijacking autophagy • Revealing the autophagy degradome and novel autophagy factors by utilizing autophagy-modulating bacteria • Identifying tissue and cell-type specific modulation of autophagy by diverse bacteria. With DIVERSIPHAGY we will reveal the holistic picture of the role of autophagy in plant-microbe interactions using a mixture of state-of-the-art approaches including metabolomics, proteomics, single-cell transcriptomics and cell-type specific reverse genetic screens. As such DIVERSIPHAGY is the next generation approach to understand the role of plant autophagy in plant-microbe interactions and by translating our results into crop plants we will be able to develop more durable resistances toward destructive pathogens.

Mots-clés : autophagy,plant microbe interactions,plant immunity,microbiome,effectors
Projet ERC : Quasicrystal (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499086.0 €

During the last fifteen years, ultracold atoms in optical lattices have emerged as a powerful model system to study the many-body physics of interacting particles in periodic potentials. The main objective of this proposal is to extend this level of control to quasiperiodic potentials by realizing an optical quasicrystal. Quasicrystals are a novel form of condensed matter that is non-periodic, but long-range ordered. They have first been observed in the 1980s by Dan Shechtman in diffraction experiments. Quasicrystals give rise to a pattern of sharp Bragg peaks, similar to periodic crystals, but with rotational symmetries that are impossible for periodic structures. Their structure was found to be given by aperiodic tilings with more than one unit cell, such as the celebrated Penrose tiling. Even though quasicrystals are long-range ordered, many foundational concepts of periodic condensed matter systems such as Blochwaves or Brillouin zones are not applicable. This places them on an interesting middle ground between periodic and disordered systems and highlights their potential for novel many-body physics. We will first characterize the optical quasicrystal using Kapitza-Dirac diffraction, and then study their unusual transport properties and relaxation dynamics after quantum quenches in the presence of interactions. We will additionally look for interesting novel phases at strong interactions and investigate the topological properties of quasiperiodic potentials. Building on my substantial expertise with optical lattices, I thus plan to build a versatile quantum simulator for the physics of quasicrystals by combining a non-periodic optical potential with ultracold Rubidium and Potassium gases.

Mots-clés : optical lattice,quasicrystal
Projet ERC : NascenTomiX (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 1999125.0 €

During the translation of genetic information into protein by the ribosome, nascent peptides occasionally inhibit their own synthesis by interacting with the exit tunnel of the large ribosomal subunit. Known as nascent chain-mediated translational arrest, this process depends primarily upon the amino acid sequence of the arrest peptide. However, it can also rely upon the sensing of a low molecular weight ligand by the ribosome nascent chain complex, explaining its use for metabolite-dependent gene regulation in both bacteria and eukaryotes. Biochemical and structural studies of arrest peptides have yielded key insights into their mode of action, but their ability to sense different types of small molecules, their impact as regulators of gene expression in nature and the precise molecular details behind the arrest process are still largely unexplored. The groundbreaking aim of this ERC Consolidator research program is to decipher the arrest code governing nascent chain-mediated translational arrest in bacteria. My approach will be based on a technique recently developed in my group, referred to here as inverse toeprinting, which precisely maps the position of an arrested ribosome nascent chain complex on the mRNA while retaining the entire peptide-coding region up to the point of stalling. The overall aim will be achieved through four complementary objectives: (i) to assess the extent to which arrest peptides can act as small molecule sensors; (ii) to identify naturally occurring arrest peptides in bacteria; (iii) to develop trans-inhibitory peptides that target the ribosome; and (iv) to perform the structural characterization of new ribosome inhibitory peptides. By addressing the natural diversity and molecular bases of the arrest process, this project will be the key to understanding a unique form of gene regulation and a fundamental aspect of ribosome function. It will also provide a handle for designing next-generation antibiotics.

Mots-clés : ribosome,protein synthesis,bacterial gene regulation,nascent chain mediated translational arrest,arrest peptides,antibiotics,antimicrobial peptides,antibiotic resistance
Projet ERC : GliomaSignals (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1875135.0 €

Dysregulated growth processes of gliomas interact with pro-epileptic plasticity of brain circuits in such a way that the excitatory transmitter glutamate promotes autocrine tumor invasion as well as epileptic synchrony in surrounding cortical regions. Most low-grade gliomas are associated with mutations of Isocitrate DesHydrogenase (IDH) genes which lead to an excess of the oncometabolite D-2-Hydroxyglutarate (D2HG). With a structure mimicking glutamate, D2HG is thought to participate in both epileptogenic and oncologic processes. Importantly, while epileptic activity is accentuated, tumor prognosis is improved in affected people. My preliminary data now suggest a dual function for D2HG, acting as a glutamatergic agonist at high levels, but as an antagonist in the presence of glutamate. Solving this paradox will be a step forward in glioma science. The GliomasSignals project will examine the role of D2HG in the neurobiology of gliomas bringing electrophysiology concepts and tools to neuro-oncology, seeking to transform our understanding. It seeks to better understand how D2HG modulates glutamatergic signaling, affects neuronal excitability and tumor growth, and to detect the extent to which tumor infiltration colocalizes with epileptic remodeling. In vivo and in vitro work mostly on human tissue will aim at: 1- Map biomarkers of epileptic activity / tumor infiltration by cortical recordings during surgery using unique next generation Neurogrid electrodes. 2- Correlate D2HG levels, glutamate concentrations and tumor infiltration with recordings in peritumoral cortex at an unprecedented resolution. 3- Identify D2HG effects on glutamate signaling in human tissue slices producing epileptic activities and in a rodent model. 4- Explore D2HG long-term effects on epileptic activity and tumor growth / infiltration in co-cultures of tumors with surrounding peritumoral cortex by exploiting our unique capabilities for long-term human cortex organotypic cultures.

Mots-clés : glioma,epilepsy,electrophysiology,human tissue,glutamate
Projet ERC : ANTILEAK (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Helsinki — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999770.0 €

Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.

Mots-clés : endothelial permeability,growth factor,vascular leakage,sepsis,angiopoietin,integrin,growth factor receptor,endothelial cell
Projet ERC : EMTECH (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Freie Universität Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1489919.0 €

EMTECH analyzes the relationship between aesthetic works on human-robot interaction in Japan and cutting-edge advances in robotics and artificial intelligence. Its central hypothesis argues that a tradition of literary, artistic, and other media forms of cultural production on human-robot relationships particular to Japan is currently being built into emotionally-intelligent companion robots with the ability to understand, record, and elicit emotions in its users, consequently expanding the capacities for humans to create affective bonds with machines and transforming structures of intimacy that sustain traditional social institutions. In its most ambitious claim, EMTECH argues that this cultural tradition has played a primary role in inspiring the recently-emerging mass production of domestic robots with technology that can register and record facial expressions, heart rate, skin conductance, and other signs of affect not consciously recognized by humans, thus generating new kinds of scientific data on human affect that fundamentally challenges previous understandings of emotion. Through the textual analysis of literary work on robot imaginaries and ethnographic fieldwork on human-robot interaction in homes, palliative care centers, and engineering laboratories, EMTECH’s purpose is to collect qualitative data on new technologies of emotion management in order to advance literary and cultural theory’s contributions to the affective sciences, as well as to inform public discussions on issues of data collection, privacy, and other ethical concerns raised by the adoption of emotionally-intelligent robots in the home. Leveraging research in the humanities to critique emotional models employed by robotics engineers and designers, and implementing novel research methods such as the use of robots in both literary critique and ethnographic fieldwork, EMTECH promises to yield groundbreaking data of both theoretical and methodological application across the human sciences.
Projet ERC : ENHANCIDO (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Perugia — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

ENHANCIDO will assess the commercial and technical feasibility of novel immune tolerance-inducing small molecules as superior treatments for multiple sclerosis (MS). MS is a chronic neurodegenerative disease affecting 2.3 million people worldwide. 85% of MS cases belong to the relapsing-remitting subtype (RRMS) characterised by bouts of recurring and debilitating relapses followed by unstoppable loss of neurological functions. Unfortunately, current treatments for RRMS are ineffective, poorly tolerated, and expensive. They cannot prevent disease progression and only provide symptomatic relief. Furthermore, severe adverse effects and inconvenient administration routes contribute to high rates of treatment discontinuation amongst patients (30-80%). To tackle these issues, Prof. Ursula Grohmann has developed a set of novel, orally administered, effective, and safe small molecules that induce immune tolerance to alter the previously inexorable course of the disease. These first-in-class molecules are positive allosteric modulators (PAMs) of the immunoregulatory enzyme IDO1. Prof. Grohmann’s PAMs increase IDO1 activity, reduce disease severity in mouse models of acute MS and show no off-target effects. Within ENHANCIDO, we will assess whether IDO1 PAMs are feasible as breakthrough treatments for RRMS. Firstly, we will validate their technical feasibility by evaluating their efficacy, pharmacokinetics and pharmacodynamics in RRMS mouse models. Subsequently, commercial feasibility will be determined by verifying IP position and strategy, performing in-depth market and competitor analyses, and finally consolidating these into a business plan to establish the best path to commercialisation. Successful commercialisation of IDO1 PAMs could reduce the profound socioeconomic burden of MS, extend and improve the lives of patients, and provide the pharmaceutical industry with a profitable, first-in-kind drug that can potentially be used for other autoimmune diseases.

Mots-clés : multiple sclerosis,allosteric modulators,immune tolerance,autoimmune disease
Projet ERC : ENUBET (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : National Institute for Nuclear Physics — Pays : Italie — Rôle : Partner
Acronyme de l'entité : INFN
Type d'entité : Recherche
Financement ERC de l'entité : 1042395.0 €

ENUBET has been designed to open a new window of opportunities in accelerator neutrino physics. The proposed project enables for the first time the measurement of the positrons produced in the decay tunnel of conventional neutrino beams: these particles signal uniquely the generation of an electron neutrino at source. Neutrino facilities enhanced by the ENUBET technique will have an unprecedented control of the neutrino flux. This will allow to reduce by one order of magnitude the uncertainties on neutrino cross sections: a leap that has been sought after since decades and that is needed to address the challenges of discovering matter-antimatter asymmetries in the leptonic sector. The apparatus is a highly specialized electromagnetic calorimeter with fast response, sustaining particle rates as high as 0.5 MHz/cm^2, having excellent electron/pion separation capabilities with a reduced number of read-out channels. ENUBET will boost technologies that have been envisaged for high energy colliders to address this new challenge. On the other hand it will operate in a substantially different configuration. The experiment will be performed at the CERN Neutrino Platform, a recently approved facility where innovative neutrino detectors will be developed exploiting dedicated hadron beam-lines from the SPS accelerator. In the first phase of the project, ENUBET will address the challenges of particle identification from extended sources, developing innovative optical readout systems and cost-effective solutions for radiation imaging. This approach is based on cutting-edge technologies for single photon sensitive devices. During the second phase, the detector will be assembled and characterized at CERN with particle beams. Finally, it will be operated in time coincidence with Liquid Argon neutrino detectors, achieving a major step towards the realization of the concept of tagging individual neutrinos both at production and interaction level, on an event-by-event basis.

Mots-clés : neutrino beam tagging positron kaon calorimeter cross section leptonic cp violation silicon photomultiplier