Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SynChI (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Pathological neuronal synchrony is the hallmark of many neurological disorders, including Parkinson’s disease (PD) and Huntington’s disease (HD), which further share deficits in cholinergic signaling. Moreover, recent findings have underscored the therapeutic relevance of the synchrony among striatal cholinergic interneurons (ChI) that orchestrate this signaling. They have shown that excessively synchronous ChI discharge induces di-synaptic release of dopamine, GABA and glutamate. Here, I propose to elucidate how ChI synchronization is generated under normal and pathological conditions and thereby identify novel therapeutic targets to treat PD and HD. This study has only very recently become feasible with the advent of powerful tools that I have mastered to explore ChI synchrony. We will employ a combination of cutting-edge in vitro and in vivo techniques to simultaneously record a far larger population of pre-identified ChIs than is currently possible. We will express GCaMP6, a genetically encoded calcium indicator (GECI), exclusively in ChIs, and use multiphoton microscopy to image calcium transients from several ChIs simultaneously in conjunction with intracellular recording from individual ChIs in acute brain slices and in anesthetized mice. Additionally, we will use endoscopic GECI imaging in freely-moving classically conditioned mice. We will employ modern analyses that reveal low-dimensional structures in large neuronal datasets to quantify synchrony (1) during on-going activity; (2) during optogenetic activation of afferents; and (3), in the freely-moving mice, while presenting conditioned cues. Finally, we will study the origins of pathological synchrony in PD and HD mouse models and explore means to correct this condition. This comprehensive approach should explain the pathological ChI synchrony observed in PD; identify novel targets to treat PD and HD; and create a general methodology to study pathological synchrony in many other neurological disorders.

Mots-clés : parkinson s and huntington s diseases,basal ganglia,acetylcholine,tonically active neurons,group i mglur,intralaminar nucleus,calcium imaging,collective neuronal dynamics,miniaturized microscopy
Projet ERC : ZAUBERKUGEL (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Paul Ehrlich was the first scientist to postulate that if a compound could be made that selectively targeted disease-causing cells, then this agent could be used for the delivery of a toxin, which would enable a pharmacotherapy of unprecedented potency and selectivity. With this procedure, a "magic bullet" (Zauberkugel, his term for an ideal therapeutic agent) would be created, that killed diseased cells while sparing normal tissues. The concept of a "magic bullet" was to some extent realized by the invention of monoclonal antibodies, as these molecules provide a very specific binding affinity to their cognate target. However, monoclonal antibodies used as single agents are typically not able to induce cures for cancer or chronic inflammatory diseases. More recently, intense academic and industrial research activities have aimed at “arming” monoclonal antibodies with drugs or cytokines, in order to preferentially deliver these therapeutic payloads to the site of disease. Unfortunately, in most cases, "armed" antibody products still cause unacceptable toxicities, which prevent escalation to potentially curative dose regimens. In this Project, I outline a therapeutic strategy, which relies on the use of extremely specific tumor targeting agents, for the selective delivery of payloads, which can be conditionally activated at the site of disease. Methodologies for the conditional generation of active payloads include the stepwise non-covalent assembly of cytokines and the controlled release of cytotoxic drugs at suitable time points after injection, when the concentration of therapeutic agent in normal organs is acceptably low. Response to therapy will be profiled using innovative proteomic methodologies, based on HLA-peptidome analysis. Pharmaceutical agents with “activity on demand” hold a considerable potential not only for the therapy of cancer, but also for the treatment of other serious diseases, including certain highly debilitating chronic inflammatory condition

Mots-clés : therapeutic antibodies,immunocytokines,antibody drug conjugates,small molecule drug conjugates,vascular tumor targeting,cancer therapy,protein engineering
Projet ERC : RRTJDM (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Warwick — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1992127.0 €

People differ in their preferences and attitudes. But how do these preferences and attitudes relate to the choices people make and the opinions they express? People’s behaviour is ubiquitously and systematically context-dependent, but cognitive and economic models of choice have failed to provide accounts that satisfactorily reconcile the context-dependence of choice with the existence of stable individual differences. In social psychology, the related person-situation debate remains largely uninformed by current cognitive models. We propose to develop a new and integrative computational model which reconceptualises the relation between preferences, choices, attitudes, and expressed opinions. We suggest that people’s choices and expressed opinions cannot be understood in terms of stable underlying preferences and attitudes in the way that conventional models assume. We propose a radically different alternative, which brings insights from social psychology to bear on cognitive models of economic judgement and choice by distinguishing between underlying preferences and expressed preferences. Underlying preferences are stable characteristics of people, but do not inform everyday choices directly because people have no conscious access to the strength of their underlying preferences. Expressed preferences in contrast are learned, context-dependent, and do inform everyday choices directly. Bringing insights from cognitive models to social context effects, we implement a parallel distinction between underlying and expressed attitudes and quantify the concepts of authenticity preference and social extremeness aversion. Using agent-based modelling to link individual-level and network-level effects, we model effects of both choice context and social context within an integrative framework, and aim to account for individual choice as well as social network-level phenomena such as social norm influences, polarisation, and social contagion effects. .

Mots-clés : models of choice,preferences,polarisation
Projet ERC : CriSP (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1479675.0 €

Percolation studies how independent random input that is spread uniformly on a lattice or in space gives rise to macroscopic structures. This model, initially introduced to understand porosity, has turned out to be central for understanding fundamental features of real-world phenomena, ranging from phase transitions in physical and chemical systems to stability of Boolean functions with respect to perturbations. Over the last sixty years, a number of important mathematical results have been obtained concerning percolation, with ideas, interactions and consequences in mathematical fields such as probability, combinatorics, complex analysis, geometric group theory, planar topology and theoretical computer science. Highlights include the rigorous derivation of a number of features that are shared with other models from statistical physics: sharpness of phase transitions, renormalization theory, existence of scaling limits and critical exponents, relationship between discrete and continuous descriptions (constructive field theory)... The story is however incomplete, as some of the most fundamental questions have not yet found a mathematical answer. Two notable examples that motivate the present research proposal are the continuity of the phase transition for Bernoulli percolation in dimension three (does the macroscopic structure appear continuously?) and the universality of planar percolation (are the macroscopic features of critical percolation in two dimensions independent of the microscopic model under consideration?). In light of very recent progress, we propose here a list of interrelated projects, with the global aim of developing new tools that should enable us to make progress towards these two open problems. The impact of this study would go beyond the percolation or statistical physics community, as we aim to provide a clean and thorough understanding of some key concepts and phenomena, that would find natural applications in other disciplines.
Projet ERC : PeroxiSystem (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Peroxisomes are ubiquitous and dynamic organelles that house many important pathways of cellular metabolism. This key organelle propagates cellular signals for differentiation, development and metabolism, and thus it is no surprise that a large number of diseases, including metabolic disorders, have been linked to peroxisomal dysfunction. Despite the importance of peroxisomes many fundamental questions remain open. For example, we do not know the entire proteome of peroxisomes, the extent of their metabolic functions, how peroxisomes change to meet cellular requirements or how they interact and communicate with other cellular organelles. In this proposal we suggest to employ our expertise and unique toolsets, successfully applied in the study of whole organelles, to shed new light on peroxisomes as a cellular unit – a PeroxiSystem. We propose to combine state-of-the art high content tools with mechanistic studies to uncover new peroxisomal proteins under a variety of growth conditions (Aim1), map the functions of unstudied peroxisomal proteins using both systematic and hypothesis driven approaches (Aim 2) and unravel how peroxisomes communicate with other organelles (Aim 3). To perform these studies we will build on expertise attained during an ERC StG: combining high throughput genetic manipulations of yeast libraries alongside high content screens. Importantly, we will try to bridge the knowledge gap in peroxisomal biology by creating new tools that can be applied to this unique organelle. Our findings should make an important step towards an unprecedented, thorough and multifaceted understanding of peroxisomes, their cellular geography and roles as well as their regulation when presented with various metabolic conditions. More broadly, the approaches presented here can be easily applied to study any organelle of choice, thus providing a conceptual framework in the study of cell biology.

Mots-clés : peroxisomes,saccharomyces cerevisiae,systematic,high content screens,protein protein interactions,genetic interactions,membrane contact sites,gfp library
Projet ERC : PainPersist (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Universität Hamburg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UHH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498294.0 €

Persistent or chronic pain is a key medical and societal problem. In the last decades, biomedical research has undertaken enormous efforts to develop treatments for persistent pain, but the results have been disappointing. This project proposes a radical shift, namely to target the early development of pain persistence and to investigate psychological interventions directed at negative expectations, control and reward in experimental long-term pain studies. A methodological work package will develop novel tools, such as MR spectroscopy of the spinal cord, to track metabolic changes related to persistent pain, and to identify the mechanisms of the proposed interventions. All studies are guided by an integrative model outlining how psychological factors, such as negative expectations and loss of control, can affect the development of pain persistence, and more importantly, how to counteract this process. We will, for example, augment the perception of pain decreases by expectations or use reward manipulations to reinstantiate the effectiveness of the pain modulatory system. Finally, the model proposes that the inability to control pain leads to a state of helplessness. Consequently, the role of helplessness will be investigated and we will test interventions with the goal to allow subjects to regain control over their pain. This will be possible, through the development of a novel pain assessment device, which can be used to detect spontaneous pain decreases and prompt the subject to perform an action (i.e. self-administer a putative treatment). Through the illusion of control, subjects perceive that their action is causal for the pain relief, even though it is actually pain reductions that trigger their action. In the future, this will also allow treatment of patients in which pain is already persistent, and allow them to regain perceived control over, and hence reduce, their pain.

Mots-clés : pain,cognitive neuroscience,neuroimaging
Projet ERC : MAGIC (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 136197.0 €

Phase contrast and scattering-based (dark-field) X-ray imaging can potentially revolutionize the radiological approach to medical imaging because they are intrinsically capable of detecting subtle differences in the electron density of a material and of measuring the effective integrated local small-angle scattering power generated by the microscopic density fluctuations in the specimen. Within the context of the ERC-Starting Grant PhaseX (310005) we deeply investigated and further developed gratings- based interferometry, a rapidly establishing phase sensitive technique. In particular, we generated seminal work towards the translation of phase contrast imaging into clinic with the world-wide first in-vitro phase-contrast mammographic investigation of whole breast mastectomies and the first reader study investigating potential clinical relevance of phase-contrast mammography. Grating fabrication is the main bottleneck so far preventing grating-based X-ray phase-contrast interferometry from being applied at high energies and large Field of View (FOV). With PhaseX, we addressed the fundamentals of grating fabrication in order to deliver high-quality diffraction gratings with high-aspect ratio. In particular, we explored unconventional fabrication techniques in order to go beyond the physical limits of the conventional approaches and we developed the idea of innovative technology at the basis of this ERC-PoC project (MAGIC). Among the tested wet etching techniques, Metal Assisted Chemical Etching (MACE) showed exceptional performances for fabrication of large area silicon gratings with high aspect ratio. The main idea of MAGIC is to use MACE for grating fabrication with characteristics that fulfil high energy and large FOV applications: we target the same quality with a competitive price in order to keep the ratio quality/cost in a favorable range with additional advantages of large FOV and possibility of serving a large market on a quicker way.

Mots-clés : x ray imaging,phase contrast imaging,diffraction gratings,microfabrication
Projet ERC : NanoMMs (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1604600.0 €

Phase-change memory (PCM) is a recently-commercialized next-generation memory storage technology that provides a sustainable solution to exponentially-growing memory storage demands of modern society. It is based on resistively switched structural changes of memory cell upon local crystallization and melting phase transitions, resulting in amorphous or crystalline atomic structures with distinctly different “0” and “1” resistance states. PCM is faster and more durable than state-of-the-art non-volatile memory devices like silicon-based solid-state drives (SSD), and it can furthermore be scaled in all three dimensions. However, there are open challenges for PCM technology, such as large power consumption and high price of PCM devices, which stem from large dimensions of memory cells, complex fabrication process, and from use of material-inefficient sputtering and etching fabrication steps for the expensive PCM layer. This proposal addresses the open challenges and enables further development of PCM technology by applying solution-based engineering. Our goals are (i) to develop robust synthetic approaches for PCM materials, such as ternary tellurides and antimony-rich compositions, in the form of colloidal nanoparticles and molecular ink precursors; (ii) to thoroughly study how PCM properties change at the nanoscale as a function of size, thickness, and composition; and (iii) to employ these phase-change nanomaterials in solution-processed PCM arrays to build new, ultrasmall PCM configurations as well as multilayer PCM cells and to reduce their price and power consumption.
Projet ERC : TOMATTO (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Madrid Institute for Advanced Studies — Pays : Espagne — Rôle : CO-PI
Acronyme de l'entité : IMDEA
Type d'entité : Recherche
Financement ERC de l'entité : 2133375.0 €

Photoinduced electron transfer (ET) and charge transfer (CT) processes occurring in organic materials are the cornerstone of technologies aiming at the conversion of solar energy into electrical energy and at its efficient transport. Thus, investigations of ET/CT induced by visible (VIS) and ultraviolet (UV) light are fundamental for the development of more efficient organic opto-electronic materials. The usual strategy to improve efficiency is chemical modification, which is based on chemical intuition and try-and-error approaches, with no control on the ultrafast electron dynamics induced by light. Achieving the latter is not easy, as the natural time scale for electronic motion is the attosecond (10-18 seconds), which is much shorter than the duration of laser pulses produced in femtochemistry laboratories. With femtosecond pulses, one can image and control “slower” processes, such as isomerization, nuclear vibrations, hydrogen migration, etc., which certainly affect ET and CT at “longer” time scales. However, real-time imaging of electronic motion is possibly the only way to fully understand and control the early stages of ET and CT, and by extension the coupled electron-nuclear dynamics that come later and lead (or not) to an efficient electric current. In this project we propose to overcome the fs time-scale bottleneck and get direct information on the early stages of ET/CT generated by VIS and UV light absorption on organic opto-electronic systems by extending the tools of attosecond science beyond the state of the art and combining them with the most advanced methods of organic synthesis and computational modelling. The objective is to provide clear-cut movies of ET/CT with unprecedented time resolution and with the ultimate goal of engineering the molecular response to optimize the light driven processes leading to the desired opto-electronic behavior. To this end, synergic efforts between laser physicists, organic chemists and theoreticians is compulsory.

Mots-clés : attosecond chemistry,electron and charge transfer,organic optoelectronics,molecular wires,attosecond pump probe,quantum chemistry of attosecond molecular science,organic synthesis,carbon nanostructures
Projet ERC : 3D-COUNT (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Sapienza University of Rome — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 76250.0 €

Photonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers. The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems. In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.

Mots-clés : integrated photonics,single photon detector,laser writing fabrication of waveguides,superconducting nanowire single photon detectors,proof of concept,communication platform,commercialisation