Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RGD-Diabetes (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Leeds — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

In Europe, 58 million people are living with type 2 diabetes and 36 million people are at risk of developing the condition. Macrovascular disease is the commonest cause of morbidity and mortality in type 2 diabetes, yet current diabetes therapies have failed to consistently reduce cardiovascular events. In my Starting Grant, I discovered that a circulating protein, IGF binding protein-1, possesses several favourable characteristics– including insulin sensitisation, amelioration of glucose intolerance, blood pressure lowering, reduced atherosclerosis and increased vascular repair. These effects are mediated by interaction of the protein’s RGD-domain with cell-surface α5β1 integrin receptors, which increases insulin-stimulated glucose uptake in skeletal muscle cells and glucose-stimulated insulin secretion in pancreatic islets. Hence the ‘idea’ from my Starting Grant is that RGD-integrin interaction could be exploited therapeutically in diabetes. In this Proof-of-Concept grant, we will take the first step towards commercialisation of the idea by designing and testing small molecule mimics of the RGD domain of IGFBP1 as diabetes therapeutics. Using in silico modelling based on the known structures of IGFBP1 and the α5β1 integrin ectodomain, we will design a small molecule library of commercially available potential agonists. We will carry out virtual high throughput screening of the library for molecules matching the shape and electrostatic potential of the RGD domain of IGFBP1 as predicted to bind to α5β1 integrin. As contingency, we will also identify in silico ‘me-too’ analogues of known integrin ligands. We will test the best quality hits through ADME profiling and validate therapeutic activity in vitro and in vivo. At the end of the project, we anticipate we will have identified small molecule RGD mimics which can subsequently be progressed through the drug-discovery pipeline through translation grant funding or pharmaceutical industry Open Innovation schemes.

Mots-clés : rgd mimetics,integrin signalling,insulin resistance,diabetes
Projet ERC : SENSOCOM (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : TU Dresden — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1056014.85 €

In Europe, approximately one hundred million people are impaired in their communication abilities. These include people with autism spectrum disorders (ca. 3 million) and individuals with dyslexia (ca. 50 million). Current neuroscience research typically associates cognitive functions including communication abilities with the cerebral cortex. By and large, this approach ignores the complex subcortical processing machinery before sensory signals reach the cortex. However, recent pioneering studies imply that dysfunction in tiny subcortical sensory structures can cause selective deficits in our ability to understand others. My goal is to (i) investigate the role of subcortical sensory structures in analysing communication signals and (ii) specify how dysfunction in subcortical-cortical interaction can cause human communication disorders. To do this we will combine very recently developed ultra-high-resolution neuroimaging with a cutting-edge multimodal approach including neurostimulation, and computational neuroimaging. The project will relate sensory subcortical responses to concrete communication behaviour, as observed in healthy individuals and individuals with communication disorders. I expect two key results: First, we will uncover the principles of how subcortical sensory structures operate for dynamic auditory and visual communication signals; this will lead to a novel model of subcortical-cortical interactions that can explain key functions in human communication. Second, the results will resolve long-standing puzzles about the nature of two of the most common hereditary communication deficits (developmental dyslexia and autism spectrum disorders). Immediate consequences of this proposal will include a translational project aimed at improving communication functions with behavioural interventions. Together, the findings may revolutionise our understanding of how sensory subcortical structures shape one of our most important cognitive functions—communication.

Mots-clés : dyslexia,sensory thalamus,predictive coding,top down modulation,cortico thalamic interaction
Projet ERC : GENDHI (Horizon 2020, appel 2019, Synergy grants)
Entité participante : École d'économie de Paris — Pays : France — Rôle : Partner
Acronyme de l'entité : EEP
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1442313.0 €

In all European countries, social inequalities in health remain pervasive. Much research has identified a number of social stratifiers of health while others have specified the role of the health care system in contributing to the evolution of health inequalities. However, gender, as a social relation of power between men and women, is rarely considered as a key determinant of health inequalities, and when it is, theoretical frameworks are rarely relevant. Furthermore, while social science studies generally ignore biological processes, sex differences in biomedical research are often interpreted as biologically irreducible. Our objective is to document and explain how gender intersects with other social hierarchies (social class and race/ethnicity) to produce social inequalities in health from early childhood to late adulthood. Adopting a life course perspective, we will examine two complementary research questions 1)"gendered embodied health" or how (un)healthy bodies are socially constructed, and 2) "gendered health care cascade" or how health-seeking behaviours and patterns of care are shaped by gender. Within this framework, we focus on hypertension and myocardial infarction, depression, Alzheimer’s disease and colorectal cancer. Our approach is resolutely multidisciplinary, associating social sciences and epidemiology, in close collaboration with clinicians. We develop triangulation analysis based on (i) secondary quantitative analysis of six large cross-sectional and cohort survey including biological markers and (ii) family monographies, interviews with youth, patients and health professionals and ethnographic observations of medical visits. The multiple working meetings to develop this project has firmed our conviction over the strength, innovative value and feasibility of this multidisciplinary, multi-method and multi-pathology project supported by four experienced researchers who are leaders in their field and internationally recognised.

Mots-clés : gender,health,inequalities,social classes,race ethnicity,lifecourse,mixed methods,ethnography,socialisation,embodiment,intersectionality
Projet ERC : VALENCE (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Minho — Pays : Portugal — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1988266.0 €

In an ever-changing environment, organisms evolved to filter information and focus on stimuli that are associated with relevant outcomes. Even the simplest animals assign valence to otherwise neutral stimuli in order to survive. A positive (rewarding) valence stimulus elicits approach, whereas a negative (aversive) valence stimulus supports avoidance behaviors. Decades of research revealed that some regions of the limbic system encode valence, including the nucleus accumbens (NAc), which is considered a prime candidate to interface valence and behavior. The NAc is mostly composed of GABAergic medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 and dynorphin, and those expressing D2 and enkephalin. D1 and D2 neurons were assumed to encode opposing valence, but recent data by us and others revealed this model to be overly simplistic. That is - to date, it is still not known how valence is encoded in this region. The main goal of this project is to determine how NAc neurons encode valence. Based on preliminary data, we hypothesize that valence is encoded by distinct patterns of MSN activity. These patterns differentially signal via GABA and opioids (dynorphin, enkephalin), triggering rewarding/aversive behaviors. To test this hypothesis, we will record neuronal activity of rodents performing tasks with opposing valences, in combination with time- and spatially-resolved analysis of opioidergic transmission, using newly-developed opioid fluorescent sensors. This information will then be used to mimic/block patterns of MSN activity and opioid events in order to show causality. This cutting-edge approach will unravel with unparalleled accuracy how NAc encodes valence, the role of endogenous opioids, and how these signals are decoded in the circuit to drive behavior. VALENCE is a frontier opening project that will answer long-standing questions in the field, deepening the knowledge on how the mammalian brain encodes rewarding and aversive events.

Mots-clés : valence,reward,aversion,nucleus accumbens,opioids,behavior
Projet ERC : ProFoundNet (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

In an ever-connected world, increasingly complex network systems play a crucial role in many daily tasks. This results in an acute need for methods/tools that can enable easy control of the network and, at the same time, provide rigorous guarantees about its behavior, performance, and security. Recent years saw the growth of a new software ecosystem -Software-defined networking (SDN)- which advocates a clean and open interface between networking devices and the software that controls them. Yet, existing SDN languages do not support reasoning about crucial quantitative aspects, such as: ``How much congestion is there?'' or ``Is the network resilient under failure?''. Enabling compositional quantitative reasoning is the major breakthrough needed to fully realize the vision of SDN. The central objective of this project is to develop new abstractions for programming of networks, with high-level modular constructs. We will provide rigorous semantic probabilistic foundations, enabling quantitative reasoning. This will serve as a solid platform for program analysis tools where compositional reasoning about complex interactions will be a reality. Our goal will be achieved through an interdisciplinary research effort: using techniques from concurrency and formal methods, areas where akin challenges can be found in the quest to design correct software systems. We will leverage the wealth of recent advances in those areas (some of which from the PI's own research) to networks, and bring awareness and new challenges arising from applications in networking to the other two communities. The project will significantly advance the foundations of network programming/verification in new and previously unexplored directions. This line of research will not only result in fundamental theoretical contributions and insights in their own right but will also impact the practice of network programming and lead to new and more powerful techniques for the use of engineers and programmers.

Mots-clés : programming languages,software defined networks,concurrency,process algebra,coalgebra,probabilistic verification,quantitative methods
Projet ERC : BADASS (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

In array-based sensing, synthetic receptors are appended with chromophores (reporters) and arrayed in various formats. The arrays are treated with analytes that displace the reporter to different extents and the outputs are interpreted by computers to identify the analyte. This has not been demonstrated for arrays of structured de novo designed peptides, which have many advantages over the synthetic small molecules currently used. Through an ERC Advanced Grant, ABEL (340764), we have designed peptides that form novel protein barrels. We have proof of principle results that show that protein barrels can be used for this kind of array sensing. Through this award, we will employ an expert peptide design chemist to address technical issues needed to translate the protein barrels into a technology platform. They will: make and test many variants of the barrels in array formats; establish the best surfaces and attachment chemistries for barrel arrays; and develop algorithms for analysing the outputs. Second, we would employ an expert in biotechnology innovation and management to conduct customer discovery to understand better the market and potential route to exploitation for our technology.

Mots-clés : array based sensing,biotechnology,coiled coil proteins,colourimetric assay,peptide arrays,protein design,protein engineering,synthetic biology
Projet ERC : NucleolusChromatin (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UZH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

In eukaryotic cells, the higher-order organization of genomes is functionally important to ensure correct execution of gene expression programs. For instance, as cells differentiate into specialized cell types, chromosomes undergo diverse structural and organizational changes that affect gene expression and other cellular functions. However, how this process is achieved is still poorly understood. The elucidation of the mechanisms that control the spatial architecture of the genome and its contribution to gene regulation is a key open issue in molecular biology, relevant for physiological and pathological processes. Increasing evidence indicated that large-scale folding of chromatin may affect gene expression by locating genes to specific nuclear subcompartments that are either stimulatory or inhibitory to transcription. Nuclear periphery (NP) and nucleolus are two important nuclear landmarks where repressive chromatin domains are often located. The interaction of chromosomes with NP and nucleolus is thought to contribute to a basal chromosome architecture and genome function. However, while the role of NP in genome organization has been well documented, the function of the nucleolus remains yet elusive. To fully understand how genome organization regulates chromatin and gene expression states, it is necessary to obtain a comprehensive functional map of genome compartmentalization. However, so far, only domains associating with NP (LADs) have been identified and characterized while nucleolar-associated domains (NADs) remained under-investigated. The aim of this project is to fill this gap by developing methods to identify and characterize NADs and analyse the role of the nucleolus in genome organization, moving toward the obtainment of a comprehensive functional map of genome compartmentalization for each cell state and providing novel insights into basic principles of genome organization and its role in gene expression and cell function that yet remain elusive.

Mots-clés : nucleolus,nuclear periphery,genome architecture
Projet ERC : NEUROEPIGENETHICS (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : KU Leuven — Pays : Belgique — Rôle : Partner
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 62500.0 €

In folk psychology and in bioethical discussions, the central dogma of genetics is often taken for granted: humans are seen as defined in a genetic blueprint. The conceptualization of psychiatric conditions as innate or acquired, biological or psychosocial, genetic or environmental, influences the ascription of both capacity responsibility (the capacity to adapt or adjust one’s own behavior) and normative responsibility of individuals or the society towards those diagnosed. But findings in the field of epigenetics indicate that the social and physical environment influence how genes are expressed. Indeed, epigenetics may shed a new light on distinctions such as innate/acquired, genetic/environmental, biological/psychosocial: a far more complex view on neurodevelopmental disorders may emerge, with ethical implications. However, the implications of epigenetics for discussions on the scope and extent of normative responsibility have not been adequately addressed. NEUROEPIGENETHICS aims to investigate the ethical implications of epigenetics for neurodevelopmental disorders. We will use theoretical and empirical methods to investigate how certain concepts (innate/biological/genetic) affect the ways in which professionals and stakeholders (persons with a neurodevelopmental disorder and their families) conceive of responsibility. We will evaluate how the emerging field of epigenetics alters the ascription of capacity responsibility and normative responsibility. We will research how individuals with Autism Spectrum Disorder (ASD), Tourette Syndrome (TS) and Attention Deficit Hyperactivity Disorder (ADHD)and their families experience the interaction between their condition and their biological and social environment. Finally, we will define moral responsibility in light of the emerging field of epigenetics in the area of neurodevelopmental disorders and child psychiatric practice.
Projet ERC : NEUROEPIGENETHICS (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Antwerp — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UAntwerp
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1390512.0 €

In folk psychology and in bioethical discussions, the central dogma of genetics is often taken for granted: humans are seen as defined in a genetic blueprint. The conceptualization of psychiatric conditions as innate or acquired, biological or psychosocial, genetic or environmental, influences the ascription of both capacity responsibility (the capacity to adapt or adjust one’s own behavior) and normative responsibility of individuals or the society towards those diagnosed. But findings in the field of epigenetics indicate that the social and physical environment influence how genes are expressed. Indeed, epigenetics may shed a new light on distinctions such as innate/acquired, genetic/environmental, biological/psychosocial: a far more complex view on neurodevelopmental disorders may emerge, with ethical implications. However, the implications of epigenetics for discussions on the scope and extent of normative responsibility have not been adequately addressed. NEUROEPIGENETHICS aims to investigate the ethical implications of epigenetics for neurodevelopmental disorders. We will use theoretical and empirical methods to investigate how certain concepts (innate/biological/genetic) affect the ways in which professionals and stakeholders (persons with a neurodevelopmental disorder and their families) conceive of responsibility. We will evaluate how the emerging field of epigenetics alters the ascription of capacity responsibility and normative responsibility. We will research how individuals with Autism Spectrum Disorder (ASD), Tourette Syndrome (TS) and Attention Deficit Hyperactivity Disorder (ADHD)and their families experience the interaction between their condition and their biological and social environment. Finally, we will define moral responsibility in light of the emerging field of epigenetics in the area of neurodevelopmental disorders and child psychiatric practice.
Projet ERC : RODRESET (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1739984.91 €

In industrialized countries, age-related macular degeneration (AMD) is the leading cause of untreatable blindness. In addition to age-related disease, there are also inherited forms of macular degeneration, such as juvenile-onset Stargardt disease. These conditions, for which there are currently no effective treatments, involve the loss of photoreceptors in the central retina, where a high cone photoreceptor density is responsible for effecting high resolution vision. We recently discovered that cones can modulate the sensitivity of surrounding rod photoreceptors to enable them to be more effective in daylight conditions. In retinal disorders involving degeneration of the macular cones, this lateral interaction is impaired, leading to saturation of the rods’ dynamic range and impaired daylight vision. We have also discovered that direct modulation the neurons underlying this lateral interaction, the horizontal cells, improves quality of vision in mice lacking functional cones. Together, our results identify a specific circuitry underlying rod-mediated vision as a potential therapeutic target following macular degeneration. Here, we aim to exploit these new findings to re-establish the rods’ ability to function in daylight using two distinct approaches. Firstly, we will use direct modification of the rods to permanently shift their light sensitivity into the daylight range. A small area of modified rods that are effective in daylight, likely with a higher temporal resolution, would improve extra-foveal fixation and vision. Secondly, we intend to establish a system that confers light sensitivity onto horizontal cells, to replace light-mediated input from cones. This will restore the natural horizontal cell-derived modulation of light sensitivity to rods, allowing them to function in daylight. Thus, by utilizing our knowledge of specific aspects of retinal circuitry, we aim to develop novel therapies for improving vision in patients with advanced macular degeneration.

Mots-clés : vision,macular degeneration,gene therapy,optogenetics