Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CONTEXTVISION (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499421.0 €

Everything occurs in a context. We see a car in the context of a street scene and a stove in the context of a kitchen. Context greatly helps the processing of individual objects. Surprisingly however, context hardly plays a role in most models of visual perception, which treat perception as a largely bottom-up categorization process. In this research proposal, I will examine how context changes the cortical computations that give rise to visual perception, focusing on contextual modulations in space and time. Moreover, I will translate this research to a clinical condition that is marked by aberrant context modulations in perception. Firstly, I will examine the influence of spatial context from the surround on cortical processing of individual elements. I aim to uncover the neural mechanisms responsible for the contextual facilitation of features and objects. I hypothesize that spatial context constrains sensory input by changing sensory representations at earlier stages in line with expectations at higher-order stages of perceptual analysis. Secondly, I will examine the influence of temporal context from past history. I hypothesize that temporal contexts trigger cortical waves of neural ‘preplay’ activity, setting up time-varying templates of expected incoming visual input. Thirdly, I will test the clinical significance of this framework to understand perceptual atypicalities in Autism Spectrum Disorder (ASD). I will empirically test the hypothesis that ASD is marked by deficient processing of contextual information, in both the spatial and temporal domain. This integrative approach has the potential to significantly advance theoretical models of perception, based on underlying neurobiology, and underline the importance of context for understanding perception. Moreover, the knowledge gleaned can have significant societal and clinical impact.

Mots-clés : context,expectation,predictive coding,object recognition,fmri
Projet ERC : FOODFORLIFE (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Medical University of Vienna — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498960.0 €

Evolutionary success drives continuous human adaptation. A pervasive challenge is the substantial change in the composition and nutritional value of diets available. This is particularly relevant for child-bearing women because metabolic bias through diet composition can adversely affects pregnancy outcomes. Even though clinical and experimental studies correlate maternal obesity during pregnancy (affecting ~30% world-wide) with congenital metabolic illnesses, a causal relationship between maternal obesity, impairment in neuroendocrine development and ensuing deficits in metabolic control of affected offspring is as yet missing. The hypothalamus is the neuroendocrine interface linking the brain and periphery. Thus, we hypothesize that maternal obesity could evoke permanent molecular changes in hypothalamic neurons of the offspring to compromise their plasticity and adaptive repertoire. This notion is on the backdrop of our recent success in defining, by singe-cell RNA-seq and brain-wide imaging, the developmental trajectory of neurons that build the mammalian hypothalamus, and in discovering the function of novel neuronal subtypes. Here, we will determine molecular, cellular and network-level changes in the hypothalamus of offspring born to obese mothers. We will combine single-cell RNA-seq and ATAC-seq in the same neurons to precisely catalogue permanent modifications to gene expression at successive developmental stages in mice. We will particularly interrogate molecular determinants that can impair the neuronal circuitry controlling food intake, including leptin and endocannabinoid interplay as a candidate. We will complement these data by identifying novel cellular sites of hormone secretion that shape brain and bodily architecture and are sensitive to maternal obesity. Overall, our work will produce new understanding of the life-long consequences of metabolic programming of the developing brain.

Mots-clés : foetal development,hypothalamus,maternal obesity during pregnancy,cellular diversity,single cell rna seq
Projet ERC : QUANTA (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of California System — Pays : Etats-Unis — Rôle : PI
Acronyme de l'entité : UC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2670247.0 €

Exact quantification, including the ability to count, depends on both conceptual breakthroughs and cognitive tools such as numeral systems. These tools appear in striking diversity across cultures and manifest in different modalities (verbal, body-based, written, or material). To address the tantalizing questions of when, why, and how they emerged and evolved, we test two previously untestable key hypotheses: that conceptual breakthroughs and tools co-evolved, with different modalities coactively scaffolding the breakthroughs; and that the tools diversified in response to changing cultural requirements. Reconstructing this evolution is the prime goal of QUANTA. Addressing its ambitious objectives requires an unprecedented synergetic combination of (i) archaeological, ethnographic, and linguistic insights into numeral systems worldwide, including prehistoric artefacts and symbols, and on contemporary contexts in which quantification occurs and changes; (ii) a cognitive framework for deriving evolutionary hypotheses from system properties; (iii) powerful computational (phylogenetic) methods for testing these hypotheses and thereby reconstructing cultural evolution; and (iv) innovative means to substantially extend the temporal scope of these methods into the past, to include the first attested instances of quantification. To achieve this goal, QUANTA brings together four leading PIs with unique and complementary expertise in exactly these means. By integrating an evolutionary approach with a cognitive perspective on quantification, QUANTA will transform this research field. Its novel strategy will, for the first time ever, yield substantiated insights into the emergence and evolution of numeral systems, thus advancing our understanding of human cognition and its dependence on cultural tools. While the highly interdisciplinary, multi-method approach renders this a high-risk project, QUANTA has the potential to bridge the gap between previously incommensurable fields.

Mots-clés : numbers,language,and mind,evolutionary anthropology,cultural evolution,phylogenetics,numerical cognition and culture,numeral systems,diversification of languages,distributed cognition,cognitive evolution,prehistory,quantification,counting devices,experimental archaeology,history of writing,notational systems
Projet ERC : RETROFIT (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2483691.0 €

Exaptation, the co-option of endogenous retroelements (EREs) for new molecular and cellular functions that confer a host fitness advantage, is a major force in evolution, but may also be exploited, through onco-exaptation, by tumour cells to promote the oncogenic process. There are over 4 million well-recognised and annotated individual ERE integrations in the human genome. However, their participation at the level of the more complex transcriptome is far less well understood and, therefore, the number of onco-exaptation events is likely vastly underestimated. To allow detection and quantitation of ERE transcription, we have recently de novo assembled the cancer transcriptome. This resulted in a doubling of the known transcriptome, particularly of unannotated or partially annotated transcripts derived from or overlapping with EREs. Here, we propose to utilise this extended view of ERE transcription as the framework for: •building a genome-wide map of functionally validated ERE onco-exaptation events and •pinpointing novel, targetable functions of EREs in immunity, cancer and their intersection Although we identified thousands of novel ERE-overlapping transcripts in cancer, the majority are likely the consequence of transcriptional activation of normally silent EREs, with little or no impact on host cell function. Impactful and inconsequential ERE integrations will be distinguished based on a number of features, including association with cancer overall survival or response to immunotherapy, impact on adjacent gene function, evolutionary conservation and functional domain and folding predictions. Postulated function will ultimately be tested extensively in in vitro cancer cell lines, ex vivo cancer patient material and in vivo mouse cancer models, tailored to the relevant onco-exaptation event. The modification of existing gene function or the creation of new function by ERE onco-exaptation will undoubtedly uncover new targets and opportunities for cancer treatment.

Mots-clés : endogenous retroelements,cancer,onco exaptation
Projet ERC : SCREENS (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Southern Denmark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : SDU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Excessive screen-based media use in young people is a clear emerging public health concern which commands serious attention and research to keep pace with the fast and profound changes in technology of screen media and how it is used. The proposed research project’s overarching objective is to investigate the immediate and long-term effects of screen-based media use on a number of important health outcomes in young people. In work package (WP) 1 and WP2 we will investigate the short-term effect of limiting screen use and timing of limiting use on circadian rhythm, sleep, physical activity patterns, and mental stress in 7-year old children and among adolescents/young adults. The WP3 of the proposed project will develop and validate a parent- and self-reported questionnaire to assess time spent (and timing of use) on different forms- and content of today’s screen media among young people and adults. We will introduce these instruments in a number of large-scale population-based cohort-studies. One of the studies will include a large birth-cohort study, which is the basis for the WP4 sub-study. The 7- and 9-year wave of the birth cohort study will provide an ideal context to investigate the long-term influence of exposure to screen-based media on physical fitness, adiposity, glucose metabolism, and mental health in children. The project will integrate multidisciplinary research into the most thorough investigation to date of the plausible short- and long-term effects of screen-based media. Through rigorously conducted randomized crossover experiments and prospective observations in a birth cohort the present project proposal will leverage methodological development of screen use assessment and new technology advancements to assess physical activity patterns, circadian rhythm, sleep, and mental stress in randomly selected young people. The project will break new ground in our understanding of the extent that today’s habitual screen use affects health of young people.
Projet ERC : BrainBIT (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Florence — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1900000.0 €

Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions. We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour. To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency. We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.
Projet ERC : ENABLE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2481744.0 €

Excising a membrane protein from its natural environment, preserving the lipid bilayer, and characterising the lipids that surround it is the ‘holy grail’ of membrane protein biophysics. However, with some 40,000 different lipid structures the challenges we face in understanding selective binding arise not just from the complexity and dynamics of the lipidome, but also from the transient nature of protein lipid interactions. To overcome these challenges we will take mass spectrometry (MS) into a new era, allowing, for the first time, the study of proteins in an environment as close as possible to the natural one. To do this we will (i) characterise protein lipid interactions by employing a high resolution Orbitrap mass spectrometer developed in-house, specifically for membrane proteins, (ii) capture the native lipid environment in vehicles suitable for use in conjunction with MS, and (iii) establish a new platform to be known as integral membrane protein desorption electrospray ionization (impDESI). Designed and built in-house impDESI is capable of releasing membrane proteins from surfaces directly into the mass spectrometer (MS). We will develop impDESI for membrane mimetics, and subsequently portions of natural membranes, enabling us to extract proteins with oligomeric state preserved and native lipid binding intact. The development of impDESI, in conjunction with high resolution Orbitrap MS, and coupled with the optimisation of membrane mimetics, has the potential to radically transform our understanding of native lipid binding, not only directly, but also temporally and spatially. Together these advances will answer key questions about how lipids modulate protein interfaces, occupy different binding sites, modulate membrane protein structure and modify function in vivo. Given the importance of membrane proteins as potential drugs targets understanding their modulation by lipids would be a major step towards more effective drug development.

Mots-clés : mass spectrometry of non covalent interactions,membrane proteins
Projet ERC : BBRhythms (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Würzburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1422907.0 €

Exciting findings from animal electrophysiological research in the last years suggest that an increased rate of body movements results in an enhanced response of neurons within the visual system despite the absence of visual changes. It is unclear why such modulation occurs in areas which process visual input. In humans, little is known about the influence of body movements on sensory brain areas mainly due to the technical challenges of measuring brain responses during pronounced muscle activity. However, psychophysical studies in humans show that also percept and perceptual demands are connected to the rate of movements. These two lines of evidence suggest a general link between rhythmic body movements and perceptual processes. The main aim of the proposed research is to decode the relationship between body movements and percept and to identify the underlying mechanism. To this end human non-invasive recordings from electro- and magnetoencephalography (EEG, MEG) as well as invasive human and animal multi-electrode recordings collected during movement execution will be analyzed. Directly relating perceptual processes and their underlying neuronal oscillations to rhythmic body movements offers an approach circumventing some of the methodological problems. This research could uncover a new mechanism of how our system modulates perceptual processes through body movements. The proof of such a mechanism would constitute a ground-breaking step in understanding perception during natural behavior. We need to keep in mind that in the awake state our body is constantly in motion. However, up to now, the vast majority of studies which investigate sensory brain responses are conducted under strict movement suppression. Besides facilitating exciting new insights, this research can strengthen the assumption that the knowledge we have gathered about artificial situations generalizes to our natural behavior.

Mots-clés : brain oscillations,ecog,subdural electrode,monkey,human,locomotion,eye movements,hippocampus
Projet ERC : PASTRES (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Institute of Development Studies — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : IDS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2145740.5 €

Existing institutions, legal frameworks and governance systems are not equipped to respond to growing global uncertainties and the challenges of building resilience. Radical new thinking is needed. Important lessons potentially can come from surprising quarters. Drawing insights from pastoral areas across three continents, we will ask: What lessons can we learn from pastoral systems responding to rapid change that help us understand how to live with uncertainty and build resilience? Learning from the margins – through a reversal in conventional policy learning and debate - this project will draw out principles from deeply-embedded, culturally-rich responses to rapid change and uncertainty in pastoral areas in Africa (Borana, Ethiopia), Asia (Qinghai-Tibet, China) and Europe (Sardinia, Italy). Working in a world-class team - including the PI (Prof. Ian Scoones), an experienced post-doctoral researcher (Dr Michele Nori) and three PhD students, together with local partners - we will explore how to respond to uncertainty and build resilience across three themes: i) environment and resources, ii) commodification and markets and iii) institutions and governance, while building the interdisciplinary research capacities of the team. Through a process of theory-building, emerging from detailed empirical research in our three sites, we will engage in dialogue with wider debates across five areas – environmental and climate change, finance and commodity markets, infrastructure design, migration policy and conflict and security - about how to respond to risk and uncertainty and build resilience, offering both new theory and practical responses. The research will significantly extend past work through a path-breaking, cross-disciplinary reconceptualization of uncertainty and resilience, linking the experiences of marginal pastoralists to wider, global resilience challenges.

Mots-clés : uncertainty,resilience,pastoralism,development
Projet ERC : CORFEDITING (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of Sheffield — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149995.0 €

Expansion of a hexanucleotide repeat G4C2 in the non-coding region of chromosome 9 open reading frame 72 (C9orf72) is the most common genetic cause for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS is a fatal condition characterized by progressive motor deficits, degeneration of upper and lower motor neurons (MNs) and death from neuromuscular respiratory failure in the majority of afflicted individuals within 3-5 years. Currently, the economic burden of care and treatment for patients with ALS/FTD is expensive and continues to significantly rise in Europe and worldwide. While significant genetic discoveries have been made in the field, they have not yet translated to treatment options for patients with ALS and FTD. Thus, research efforts aimed at identifying therapeutic targets are of the utmost importance to enable therapeutic development for these devastating disorders. In this ERC Proof of Concept project, we will design, optimise and test gene therapy vectors containing CRISPR/Cas9 system to selectively remove the pathogenic ALS/FTD-related C9orf72 hexanucleotide repeat expansion in mouse models of C9orf72-related ALS, with the ultimate aim of designing a therapy for patients with C9orf72-related ALS/FTD. The ultimate benefit of this approach goes far beyond just ALS/FTD however. A successful CNS gene therapy for C9orf72 related disease potentiates the prospect of developing similar approaches to treat multiple disease scenarios amenable to gene modification. Indeed, growing evidence suggests that C9orf72 repeat expansions also contribute to a wide spectrum of neurodegenerative diseases such as Alzheimer’s, Huntington’s, multiple sclerosis, Parkinson’s disease and cerebellar ataxias. We therefore anticipate that our strategy could be beneficial for other neurological conditions.

Mots-clés : neurodegeneration,gene therapy,gene editing