Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SupraCTRL (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

The biochemical and biophysical cues of the stem cell environment that act in a concerted and spatiotemporal manner lead to the formation of the 200 cell types and organs of the human body, but how this precisely occurs remains unclear and it is necessary to guide their production for use in the biomedical area. Standard differentiation protocols in vitro mimic known stages in development by the timed addition of biochemical cues on 2D substrates, however these protocols lack the complexity of the 3D natural extracellular matrix (ECM), with its mechanical character that evolves in time. Supramolecular materials can recapitulate the structural and dynamic character of the ECM being based on non-covalent interactions. Moreover, as I have shown, their mechanical soft character can mimic embryonic microenvironment for induced pluripotent stem cell (iPSC) culture but renders them unable to mimic stiff and tough tissues. Double networks using covalent polymers have demonstrated to achieve such mechanical properties, however these materials lack the cytocompatibility for use in 3D cell culture. In this proposal, I will synthesize hybrid covalent-supramolecular polymer networks that use biocompatible chemical and light-activated ligation approaches to apply them to guide the fate of iPSCs to cardiomyocytes by controlling their mechanical properties in time. I will exploit the unique properties of these double networked materials to interface them with biomechanical devices, and as an actuatable culture platform by 3-D printing a miniature beating heart ventricle. These advanced culture platforms based on hybrid-covalent supramolecular materials that go from soft to stiff and tough in time and space with shifting-shapes, with the potential to decouple the presentation of bioactive cues in an integrated manner, will provide uncharted opportunities to understand the spatiotemporal evolution of active and passive mechanical cues in development from cell to organ.
Projet ERC : PHONOMETA (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Carlos III University of Madrid — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1325158.0 €

The boost experienced by acoustic and elastic (phononic) metamaterial research during the past years has been driven by the ability to sculpture the flow of sound waves at will. Thanks to recent developments at the frontiers of phononic metamaterials it can be identified that active phononic control is at the cutting edge of the current research on phononic metamaterials. Introducing piezoelectric semiconductors as a material platform to discover new avenues in wave physics will have the potential to open horizons of opportunities in science of acoustic wave control. Electrically biased piezoelectric semiconductors are non-reciprocal by nature, produce mechanical gain and are highly tunable. The aim is to explore novel properties of sound and the ability to design Parity-Time (PT) symmetric systems that define a consistent unitary extension of quantum mechanics. Through cunningly contrived piezoelectric media sculpturing balanced loss and gain units, these structures have neither parity symmetry nor time-reversal symmetry, but are nevertheless symmetric in the product of both. PHONOMETA is inspired and driven by these common notions of quantum mechanics that I wish to translate into classical acoustics with unprecedented knowledge for the case of sound. I expect that the successful realization of PHONOMETA has the potential to revolutionize acoustics in our daily life. Environmental and ambient noise stem from multiple scattering and reflections of sound in our surrounding. The extraordinary properties of PT acoustic metamaterials have the groundbreaking potential to push forward physical acoustics with new paradigms to design tunable diode-like behaviour with zero reflections, which is applicable for noise pollution mitigation. Also I anticipate to impact the progress on invisibility cloaks by introducing PT symmetry based acoustic stealth coatings for hiding submarines.
Projet ERC : MICRO-COPS (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

The brain controls all body functions. At the base of this 'catholic' role are the neurons, cells that generate electrical signals, communicate via synapses and form circuits that execute computing tasks and control behaviour. The electrical signalling pattern of neurons is the information code of the brain and the synapse connectivity determines circuit function. This is, in brief, what most textbooks emphasise, but such a neuron-centred brain view is precariously short-sighted. Apart from neurons, the brain contains three glia cell types (from Greek 'γλία' for 'glue'): astrocytes, oligodendrocytes, and microglia. But far from being mere 'glue', astrocytes and oligodendrocytes have multiple critical functions in the brain, accordingly affect many brain processes - even genuine computing tasks - and have therefore become a major focus of modern neuroscience. Microglia are the 'odd one out'. They are brain-resident immune cells, act as defence against pathological insults and have a housekeeping function as phagocytes. Aside from these functions, microglia seem to play an as yet unrecognized role by engaging in reciprocal signalling with neurons. It is this Microglia Control of Physiological Brain States we will study in MICRO-COPS, based on the hypothesis that microglia purposively control neuronal function. We will combine mouse genetics with cutting-edge gene expression analysis and cell biological, electrophysiological, and imaging technologies to define the reciprocal microglia-neuron signalling pathways, the signalling molecules involved, the biological consequences for microglia and neurons, and the role of the corresponding signalling processes in synapse physiology, neuronal integration, circuit dynamics, and behaviour. We expect that the mechanistic description of reciprocal microglia-neuron interactions - from synapses to circuits - will establish a new and critically important brain regulatory process and provide key insights into brain pathology.

Mots-clés : reciprocal microglia neuron signalling,synapses,circuits,microglia electrophysiology,microglia secretion
Projet ERC : BRAINSTRUCT (Horizon 2020, appel 2014, 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 : Partner
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 563947.5 €

The brain is an extraordinary complex assembly of neuronal and glial cells that underpins cognitive functions. How adequate numbers of these cells are generated by neural stem cells in embryonic and early postnatal development and how they distribute and interconnect within brain tissue is still debated. In particular, the potentialities of individual neural stem cells, their potential heterogeneity and the mechanisms regulating their function are still poorly characterized in situ; likewise, the clonal architecture of mature brain tissue and its influence on neural circuitry are only partially explored. Deciphering these aspects is essential to link neural circuit development, structure and function, and to understand the aetiology of neurodevelopmental disorders. We have recently established transgenic strategies to simultaneously track the lineage of multiple individual neural stem cells in the intact developing brain and experimentally perturb their development. We will use these approaches in combination with recent large-volume imaging methods for high-throughput analysis of individual neural and glial clones in the mouse cortex. This will allow us to assay neural progenitor potentialities and equivalence, characterize developmental changes occurring in the neurogenic niche, describe the clonal organization of the mature cortex and study its link with neural connectivity. To decipher intrinsic and extrinsic mechanisms regulating neural progenitor activity and understand how they produce appropriate numbers of cells, we will assay the outcome of functional perturbations targeting key steps of neural development, introduced in precursors or in their local environment. These experiments will reveal how neural stem cell output might be regulated by cell interactions and intercellular signals. This multidisciplinary project will set the basis for quantitative analysis of brain development with single-cell resolution in normal and pathological conditions.

Mots-clés : lineage tracing,genetic engineering,large volume imaging,fluorescence microscopy
Projet ERC : CONNECT (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Vrije Universiteit Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : VU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999955.0 €

The brain is one of the most complex living systems we know and has an enormous capacity to regulate our physiology, behaviour and cognition. 30% of the European population however has to deal with a mental challenge, ranging from depression to burnout to psychosis, etcetera. These conditions are traditionally seen as separate disorders, but there is growing evidence that many mental conditions share overlap in terms of their genetics and symptomatology. The brain mechanisms behind this cross-disorder overlap reflecting a common biological factor of mental conditions remains unknown. One of the key problems is that the current field is centralised around ‘single-condition examinations’, lacking specificity and selectivity of macroscale mechanisms, leaving us blind for which brain attributes play a common versus a unique role across and within mental conditions. The goal of CONNECT is to find an underlying shared biological mechanism of mental conditions: I hypothesise that the organizational principles of the healthy brain network form a common network system for shaping relationships across disorders. With CONNECT I want to map the total brain space of cross-disease relationships to disentangle shared and specific mechanisms of cognitive function and disease disfunction. I want to build (WP0) a large multi-disorder MRI database to compare (WP1) brain fingerprints across a wide range of conditions. I will (WP2) develop a mechanistic framework to fundamentally describe cross- condition interactions and model the shared mechanisms of involvement of brain networks in brain function. This model will be leveraged into (WP2/3) a comprehensive connection catalog that systematically maps for all circuitry their common vs unique role in cognitive functions and their subsequent involvement in the spectrum of mental conditions. Disentangling disease-common from disease-specific effects, I will use Machine Learning to pave the way for (WP4) ‘prediction connectomics’.

Mots-clés : neuroimaging,systems biology,network neuroscience,complexity
Projet ERC : ErasingFear (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498328.0 €

The breakthrough discovery in animal research that fear memories may change upon retrieval – referred to as memory reconsolidation – has drastically changed the view on the malleability of emotional memory. Inspired by these insights, we have developed a novel approach to pharmacologically erase the affective component from fear memories in humans. Although these findings suggest a paradigm shift in clinical practice, there are many fundamental questions to be resolved. The objective of this proposal is to gain an in-depth, comprehensive understanding of the dynamic balance between the stability and malleability of emotional memory, and consequently develop a revolutionary theory-driven treatment for emotional memory disorders. This program presents a novel mechanistic framework on memory reconsolidation challenging in several ways the dominant model of emotional memory modification. First, while during traditional interventions cognitive changes are required for a reduction in fear, in our procedure cognitive changes preclude the neutralization of fear memory. On the other hand, post-retrieval changes in the cognitive (WP1) and neural (WP2) expression of fear memory may serve as read-outs to demarcate the underlying processes necessary for memory reconsolidation. Second, in contrast to the immediate, but gradual decline of fear during traditional interventions, with memory reconsolidation the fear reduction is delayed, yet abrupt, and sleep may be essential (WP3). A thorough understanding of these processes is essential for developing a reconsolidation intervention in clinical practice (WP4). Finally, the program aims to understand the paradoxical dissociation, yet interdependence, between the cognitive and emotional expressions of fear memory (WP5). This proposal is unique in its bidirectional translational approach. It involves different levels of analysis: from behavioural science, to neuroscience to clinical science, and backwards.

Mots-clés : fear memory,memory reconsolidation,fear conditioning,fear extinction,fmri,sleep,anxiety disorders,ptsd,treatment for anxiety disorders
Projet ERC : INFERTILITY (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Norwegian Institute of Public Health — Pays : Norvège — Rôle : PI
Acronyme de l'entité : NIPH
Type d'entité : Recherche
Financement ERC de l'entité : 1479676.0 €

The burden of infertility is high across Europe. Modest evidence indicates that infertile couples might have an increased risk of cardiovascular disease (CVD), but several questions need clarification to establish a cause-and-effect relationship. This includes understanding: whether both infertile men and women have an increased risk of CVD; how well-known risk factors for CVD (blood-pressure, body-mass index, cholesterol and smoking) relate to infertility; whether there exists common genetic determinants of infertility and CVD; and whether the connection between infertility and CVD in women can be explained by the use of assisted reproductive technologies or pregnancy complications. These questions will be answered by the INFERTILITY project. The working hypothesis of INFERTILITY is that both infertile men and women have an increased risk of CVD, and that this might at least partly reflect a greater burden of CVD risk factors. I will test this by using data from cohort studies and national health registries in Norway and the United Kingdom. I will use genetic markers as instrumental variables to establish the relationship between CVD risk factors and infertility. This is vital to understand whether infertile couples truly have an increased risk of CVD or whether infertility instead reflects a pre-existing propensity for CVD. I will conduct a genome-wide association study of infertility and identify overlapping genetic markers between any findings from this investigation and published studies of CVD. The INFERTILITY project will also clarify whether offspring cardiometabolic health trajectories differ according to parental fertility problems. This will highlight whether any relationship between infertility and CVD also crosses generations. The INFERTILITY project will elucidate whether infertile couples should be followed more closely to mitigate their risk of CVD and whether interventions targeting well-known CVD risk factors could reduce the burden of infertility.
Projet ERC : iDysChart (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : St Anna Children's Hospital — Pays : Autriche — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 0.0 €

The central challenge for the immune system is to efficiently recognize and neutralize foreign antigen while protecting self. If the latter fails, autoimmunity and/or autoinflammation may occur, as observed in many human diseases. Though several human genes involved in the process have been identified we still lack: i) a comprehensive appreciation of all contributing molecular pathways, ii) an understanding of the interplay and epistatic relationships among the various elements and iii) a satisfactory strategy to counteract dysregulation based on an understanding of the regulatory logic. I hypothesize that there is only a finite number of pathways involved and that it should be possible to mount a synergistic strategy to create a first chart of the entire “territory”. Key to this endeavor is the identification of sufficient elements by mapping immune dysregulation genes to “anchor” the chart onto signposts of which the human pathophysiological relevance is certain. From these signposts, contextualization and integration is achieved by interaction proteomics and network informatics mining the existing data universe, validated through biochemical and imaging tools to power an established set of immune assays. While it may be preposterous to claim feasibility with one ERC grant, I propose that once such a chart exists, even at initial low resolution, it can help reconcile disconnected observations and coalesce future work while being immensely improved in accuracy and mechanistic understanding by the entire community. iDysChart will work towards these goals by 1) identifying novel monogenic causes of autoimmune/autoinflammatory diseases, enabling elucidation of fundamental mechanisms, 2) creating a network-level understanding of molecular pathways of immune dysregulation and 3) employing chemical and genetic screens to complement human disease gene discovery in predicting the core human immune dysregulome and investigating potential avenues for therapeutic modulation.

Mots-clés : inborn error of immunity,immunodeficiency
Projet ERC : TIDE (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 973380.39 €

The central research question this project will pose is: how did mobility in the great age of travel and discovery (c.1550–1700) shape English perceptions of human identity based on cultural identification and difference? The role of those marked by transcultural mobility was central to this period. Our current world is all too familiar with the concepts that surfaced or evolved as a result: ‘foreigners’, ‘strangers’, ‘aliens’, ‘converts’, ‘exiles’, or even ‘translators’, ‘ambassadors’ and ‘go-betweens’. There is an urgent need to consolidate our fragmented understanding of this crucial issue, which continues to shape current debates. TIDE offers a direct and timely response to this challenge, combining established methodologies with a set of ambitious and innovative approaches. By bringing together multiple discourses that tackled the fraught question of human identity in this era, ranging across literature, trade, diplomacy, governance, law, religion and ethnography, it will open a new perspective on cross-cultural encounters. It will put pressure on our understanding of cultural difference, transculturality and identity, and generate a new understanding of key terms, concepts, and debates. It will produce new knowledge about the unique role played by literature, and break fresh ground through the combination of academic research with new writing. Its returns would be significant: a fundamental improvement to our current understanding of cultural differentiation and assimilation, as well as a lasting and creative insight into their consequences.

Mots-clés : renaissance,travel law,religious studies,trade,diplomacy,migration,identity
Projet ERC : NeuroCentro (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Helmholtz Zentrum München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HMGU
Type d'entité : Recherche
Financement ERC de l'entité : 2256834.0 €

The centrosome is a crucial cellular organelle involved in many functions especially during development where it acts to regulate key processes, such as cell division, cilia formation and migration. While many mutations in centrosome-associated proteins lead to diseases often predominantly affecting the brain, the basis for this specificity is in most cases not known. Likewise, basic aspects of centrosome biology, such as the role of RNAs at the centrosome, are largely unknown. Our recent discovery of novel centrosome-associated proteins in human neural stem cells revealed specific RNA-binding proteins at the sub-distal appendages of centrosomes with significant and selective associations to periventricular heterotopia (PH), a neuronal migration disorder. This provides a unique entry point to explore, in the first part of this project, fundamental questions associated with the role of RNAs and RNA-binding proteins at the centrosome and their contribution to neurodevelopmental disorders. In the second part, we will explore changes in centrosome composition from NSCs to young migratory neurons and identify the role of the centrosome in neuronal subtype-specific migration modes using the novel centrosome protein Akna as entry point. In the third part, we will utilize our advanced tools for dCas9 multiplexed transcriptional engineering to restore centrosome function of ectopic neurons and revert migration defects causing PH. These rescue attempts will be extended to later stages of development aiming to revert differentiated glia, the ependymal cells, to radial glial cells, that serve as guides for migrating neurons. This work will thus tackle fundamental functions of neural-specific centrosome proteins, laying the basis to understand the brain-specific phenotype of mutations in factors that are widely expressed but predominantly affect the brain.

Mots-clés : neural stem cells,neurogenesis,neuronal migration,centrosome