Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RETMUS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University Hospital of Basel — Pays : Suisse — Rôle : PI
Acronyme de l'entité : USB
Type d'entité : Recherche
Financement ERC de l'entité : 170630.0 €

Sensory systems of the brain inform cortical centers about the outside world via the thalamus. Despite its central location between the sensory periphery and the primary sensory cortex, the functional role of the thalamus in sensory processing is still largely unknown. Understanding the role of thalamic circuits and their modulation by other brain areas is important for several reasons. First, in order to dissect the functional role of higher brain regions, such as sensory cortical areas, it is critical that we understand what kind of input they receive from the thalamus. The thalamus takes information from several different sensory channels, carrying different sensory features. Whether these features are simply relayed to higher centers, or perhaps recombined into new features in the thalamus, is not known. Second, as a central station in sensory processing, the thalamus is thought to gate behaviorally relevant sensory information. In addition to the input from the sensory periphery, the thalamus receives input from several other brain regions. How these inputs modulate or gate sensory information in vivo is not well understood. Finally, in the case of the visual system, an important unmet medical need is optic nerve degeneration caused by end-stage glaucoma, which leads to blindness. Here the input to thalamus is lost, yet the thalamic and cortical circuits are not severely affected. New methods to reactivate the thalamic neurons by channeling visual information directly to these neurons may help to restore some visual capability after the loss of optic nerve fibers.

Mots-clés : viral tracing,two photon imaging,retina
Projet ERC : Serial-X (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Gothenburg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Serial-X aims to expand of the use of serial crystallography across the academic and industrial life-science community by introducing low cost, flexible and easy to use solutions to the most common problems that occur in serial crystallography experiments today. Serial crystallography is a developing method of macromolecular X-ray crystallography that allows diffraction data to be collected at room temperature from a continuous stream of microcrystals. “ProtonPump”, the ERC Advanced Grant awarded to Richard Neutze, applies time-resolved serial crystallography to observe structural changes that occur during the reduction of molecular oxygen to water by cytochrome c oxidase. This PoC builds directly from technical solutions developed to achieve the scientific goals of “ProtonPump”. Serial crystallography was first developed at an X-ray free electron laser but is increasingly being used at synchrotron radiation facilities. Synchrotrons can potentially support up to two orders of magnitude more serial crystallography users than X-ray free electron lasers. Synchrotron based serial crystallography experiments may also become a mainstream method in structure-based-drug-design. But these possibilities will not be realized if the current lack of standardization in sample delivery continues, which is currently prohibitively expensive and requires a high level of technical support to operate. Serial-X will solve this problem by developing and bringing to market standardized, low-cost, flexible and easy-to-use solutions for sample delivery in serial crystallography studies at synchrotron radiation sources. Serial-X will thereby remove the greatest obstacle currently preventing scientists from using serial crystallography for their own research or for structure based drug-design within a pharmaceutical drug discovery context. A spin off company will be formed to manufacture and distribute the technologies developed within this Proof of Concept Grant.

Mots-clés : serial crystallography,synchrotron radiation,time resolved crystallography
Projet ERC : VEGFDANI (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Heidelberg University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 147968.0 €

Several forms of neuroadaptation are controlled by transient increases in the nuclear calcium concentration. Nuclear calcium regulates expression of crucial genes and alterations of this signaling network likely underlie many neurological disorders. Our work led us to design two innovative strategies exploiting the therapeutic potential of nuclear calcium signaling: 1-developing direct nuclear calcium signaling activators/inhibitors (NCSA/I) and 2-manipulating expression and/or function of nuclear calcium targets. The proposed activities and budget - taking the ERC-PoC stroke study as the model project – will be used to meet the essential pre-commercial requirements prior starting up a company focusing on early drug discovery in the area of targeted nuclear calcium signaling modulation: R&D objectives: 1-PoC to validate our lead mimicking a stroke-protective regulator: VEGFD; 2-Add novel drug targets & assays and transfer to screening partner; 3-Mass screening and lead validation to expand IP; Business objectives: 1-Manage emerging IP platform; 2-Complete fund raising during ERC funding period; 3-Close early drug discovery partnership. As part of the ERC project 233024, we identified a nuclear-calcium dependent gene, VEGFD, as a new anti-stroke drug target. We showed that VEGFD regulates neuronal morphology and cognition and demonstrated that VEGFD delivery in the mouse brain prevents stroke-induced dendritic loss and promotes long-term recovery. We selected a highly biologically active VEGFD peptide mimetic (VPM) as our first lead for a conceptually novel nasal spray stroke therapy. Senior business experts advised and helped us to establish a business plan and to pre-negotiate collaborative partnerships with companies and institutions required to deliver on our objectives. Thus, by partnering with industry professionals we were able to define a clear go-to-commercialization strategy while minimizing risks originating from possible lack of business experience.

Mots-clés : stroke,functional recovery,vegfd,nuclear calcium signaling,nasal spray,peptides,screening,novel drug target
Projet ERC : OscillatoryVision (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Aarhus University — Pays : Danemark — Rôle : PI
Acronyme de l'entité : AU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499850.0 €

Several sophisticated image processing circuits have been discovered in the animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, but electroretinography (ERG) has not been tapped to examine this potential in humans. Bolstered by our compelling results combining ERG with magnetoencephalography (MEG), this project will address several open questions with respect to human visual processing: 1) Could variable retinal timing be linked to intrinsic image properties and pass on phase variance downstream to visual cortex? Our data suggests the retina responds to moving gratings and natural imagery with non-phase-locked high gamma oscillations (>65 Hz) just like visual cortex, and that slower ERG potentials exhibit strong phase-locking within stimuli but large phase variance across stimuli. 2) Do such retinal gamma band responses, both evoked and induced, directly drive some cortical gamma responses? Pilot data suggests that it can, through retinocortical coherence, our novel ERG-MEG mapping technique. 3) Several kinds of motion have now been shown to elicit massive synchrony in mammalian retina circuits. Does this also result in macroscopic high-frequency activity? If so, our experiments will finally reveal and characterize motion detection by the human retina. 4) Do efferent pathways to the retina exist in humans? We discovered that the ERG exhibits eyes-closed alpha waves strikingly similar to the classic EEG phenomenon and, leveraging our retinocortical coherence technique, that this activity is likely driven by contralateral occipital cortex. Then, can retinal responses be influenced by ongoing cortical activity? Characterizing retinocortical interaction represents a complete paradigm shift that will be imperative for our understanding of neural synchrony in the human nervous system and enable several groundbreaking new avenues for research.

Mots-clés : gamma band,neural synchrony,induced oscillations,neural connectivity
Projet ERC : ASICA (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 264398.75 €

Severe droughts in Amazonia in 2005 and 2010 caused widespread loss of carbon from the terrestrial biosphere. This loss, almost twice the annual fossil fuel CO2 emissions in the EU, suggests a large sensitivity of the Amazonian carbon balance to a predicted more intense drought regime in the next decades. This is a dangerous inference though, as there is no scientific consensus on the most basic metrics of Amazonian carbon exchange: the gross primary production (GPP) and its response to moisture deficits in the soil and atmosphere. Measuring them on scales that span the whole Amazon forest was thus far impossible, but in this project I aim to deliver the first observation-based estimate of pan-Amazonian GPP and its drought induced variations. My program builds on two recent breakthroughs in our use of stable isotopes (13C, 17O, 18O) in atmospheric CO2: (1) Our discovery that observed δ¹³C in CO2 in the atmosphere is a quantitative measure for vegetation water-use efficiency over millions of square kilometers, integrating the drought response of individual plants. (2) The possibility to precisely measure the relative ratios of 18O/16O and 17O/16O in CO2, called Δ17O. Anomalous Δ17O values are present in air coming down from the stratosphere, but this anomaly is removed upon contact of CO2 with leaf water inside plant stomata. Hence, observed Δ17O values depend directly on the magnitude of GPP. Both δ¹³C and Δ17O measurements are scarce over the Amazon-basin, and I propose more than 7000 new measurements leveraging an established aircraft monitoring program in Brazil. Quantitative interpretation of these observations will break new ground in our use of stable isotopes to understand climate variations, and is facilitated by our renowned numerical modeling system “CarbonTracker”. My program will answer two burning question in carbon cycle science today: (a) What is the magnitude of GPP in Amazonia? And (b) How does it vary over different intensities of drought?

Mots-clés : carbon cycle,carbon uptake,stable isotopes
Projet ERC : ASICA (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Wageningen University & Research — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : WUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 827975.0 €

Severe droughts in Amazonia in 2005 and 2010 caused widespread loss of carbon from the terrestrial biosphere. This loss, almost twice the annual fossil fuel CO2 emissions in the EU, suggests a large sensitivity of the Amazonian carbon balance to a predicted more intense drought regime in the next decades. This is a dangerous inference though, as there is no scientific consensus on the most basic metrics of Amazonian carbon exchange: the gross primary production (GPP) and its response to moisture deficits in the soil and atmosphere. Measuring them on scales that span the whole Amazon forest was thus far impossible, but in this project I aim to deliver the first observation-based estimate of pan-Amazonian GPP and its drought induced variations. My program builds on two recent breakthroughs in our use of stable isotopes (13C, 17O, 18O) in atmospheric CO2: (1) Our discovery that observed δ¹³C in CO2 in the atmosphere is a quantitative measure for vegetation water-use efficiency over millions of square kilometers, integrating the drought response of individual plants. (2) The possibility to precisely measure the relative ratios of 18O/16O and 17O/16O in CO2, called Δ17O. Anomalous Δ17O values are present in air coming down from the stratosphere, but this anomaly is removed upon contact of CO2 with leaf water inside plant stomata. Hence, observed Δ17O values depend directly on the magnitude of GPP. Both δ¹³C and Δ17O measurements are scarce over the Amazon-basin, and I propose more than 7000 new measurements leveraging an established aircraft monitoring program in Brazil. Quantitative interpretation of these observations will break new ground in our use of stable isotopes to understand climate variations, and is facilitated by our renowned numerical modeling system “CarbonTracker”. My program will answer two burning question in carbon cycle science today: (a) What is the magnitude of GPP in Amazonia? And (b) How does it vary over different intensities of drought?

Mots-clés : carbon cycle,carbon uptake,stable isotopes
Projet ERC : iPROTECTION (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Calouste Gulbenkian Foundation — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1985375.0 €

Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options outside of infection control and organ support measures. Based on our recent discovery that anthracycline drugs prevent organ failure without affecting the bacterial burden in a model of severe sepsis, we propose that strategies aimed at target organ protection have extraordinary potential for the treatment of sepsis and possibly for other inflammation-driven conditions. However, the mechanisms of organ protection and disease tolerance are either unknown or poorly characterized. The central goal of the current proposal is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines as a window into stress-induced genetic programs conferring disease tolerance. To that end, we will carry out a combination of candidate and unbiased approaches for the in vivo identification of ATM-dependent and independent mechanisms of tissue protection. We will validate the leading candidates through adenovirus-mediated delivery of constructs for overexpression (gain-of-function) or shRNA for gene silencing (loss-of-function) to the lung, based on our recent finding that rescuing this organ is essential and perhaps sufficient in anthracycline-induced protection against severe sepsis. The candidates showing the most promise will be characterized using a combination of in vitro and in vivo genetic, biochemical, cell biological and physiological methods. The results arising from the current proposal are likely not only to inspire the design of transformative therapies for sepsis but also to open a completely new field of opportunity to molecularly understand core surveillance mechanisms of basic cellular processes with a critical role in the homeostasis of organ function and whose activation can ultimately promote quality of life during aging and increase lifespan.

Mots-clés : sepsis,anthracyclines,dna damage responses,disease tolerance,lung,cytoprotection
Projet ERC : HOW2WALKAGAIN (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1998715.0 €

Severe spinal cord injury leads to a range of disabilities, including permanent motor impairments that seriously diminish the patients’ quality of life. In the framework of an ERC Starting Grant, my team and I developed a pragmatic therapy that restored supraspinal control of leg movement after complete paralysis in rats. However, the mechanisms underlying the effects of this intervention remain unknown. This fundamental knowledge is pivotal to operate a disruptive conversion from our empirical approach to an evidence-based strategy with clinical perspectives. Our therapy, termed neuroprosthetic rehabilitation, acts over two time windows. Immediately, electrical and chemical spinal cord stimulations mediate motor control of the paralysed hindlimbs. In the long term, will-powered training regimens enabled by electrochemical stimulation and robotic assistance promote neuroplasticity of residual connections—an extensive rewiring that reestablishes voluntary movement. Here, we propose to identify the circuit-level remodelling, computational principles, and molecular cues that govern the immediate and long-term recovery of motor functions. To address this knowledge gap, we will use our unique neuroprosthetic platform and next-generation experimental techniques for longitudinal assessment of neuroplasticity and function in freely behaving mice. These techniques combine optogenetics, circuit-level inactivation techniques, unconstrained chronic calcium imaging, virus-mediated tract-tracing and genetic manipulations. Our strategy consists of deploying a judicious association of these experimental techniques to establish causality between the reorganisation of the motor circuitry and functional recovery. This project will fertilize frontier research with new knowledge and ideas, ultimately accelerating clinical implementation of safer and more efficacious therapies to improve the quality of life for spinal cord injured individuals.

Mots-clés : neurorehabilitation,neuromodulation,robotics,locomotion,neuroplasticity,bdnf,spinal cord injury,mice
Projet ERC : IntraGutSex (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2485217.0 €

Sex differences in intestinal plasticity Males and females often differ in their physiology and disease susceptibility. Sex hormones play key roles in sculpting and maintaining such sex differences, but increasing evidence points to a contribution of cell-intrinsic mechanisms. We are only beginning to understand the molecular mediators of these intrinsic mechanisms, and little is known about the organs where they function and their effects at the whole-organism level. Our work in flies recently revealed the existence of intrinsic sex differences in intestinal stem cell proliferation. This work raised the possibility that other, more metabolically significant intestinal cell types have their own sexual identity, with potential consequences at the organ and whole-organism levels. This proposal will explore the nature and significance of this sexual identity in two such cell types: enterocytes and neurons. We will first take advantage of our ability to genetically manipulate and sexually transform these cells in Drosophila in order to understand how their sexual identity is specified and whether it needs to be actively maintained. We will then explore the contribution of such sexual identity to organ features and whole-body physiology. Finally, we will investigate the evolutionary conservation of our findings by establishing organoids as a model to investigate enterocyte physiology, and then use them to explore whether intrinsic mechanisms are also active in the mouse intestinal epithelium. Collectively, our multidisciplinary approach will shed light on the contribution of the intestine - an organ not previously known to have an intrinsic sexual identity - to sex differences in physiology. It will also pioneer the study of enterocyte physiology in organoids: an emerging and extremely powerful ex vivo system. Our work will also lay the foundations for future interventions aimed at tackling sex biases in disease susceptibility/prognosis.

Mots-clés : drosophila,intestine,enteric neurons,sex differences,organoids
Projet ERC : TETHYS (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1835517.5 €

Sexual reproduction is a pervasive phenomenon that produces new genetic combinations in nearly all eukaryotic lineages. Whilst the core processes that define meiotic sex (meiosis and syngamy) are universal, sex determination systems are not evolutionary conserved but are bewilderingly diverse and have had rapid turnover rates during evolution. Transitions among sex determination systems have profound evolutionary and ecological consequences, but our understanding of the mechanisms, ultimate causes, and the consequences of transitions is still surprisingly incomplete. The goal of the Tethys project is to exploit the exceptional richness of sexual features of the brown algae to gain novel insights into the functional bases and ultimate forces associated with transitions between sexual systems, and their impact on the evolution of this important group of eukaryotes. First, we will exploit the amenability of model brown algae to genetic and genomic approaches to uncover the mechanisms and evolutionary forces driving switches between sexual systems across this group. Secondly, we will investigate the regulation and evolution of the genes involved in sexual reproduction in the context of sexual system transitions, by delineating a comprehensive transcriptional and chromatin state roadmap across key brown algal species. Finally, we will examine patterns of correlated evolution between sexual, functional and genomic traits and incorporate ecological information in order to link ecological factors to reproductive transitions and evaluate their consequences on genome structure and species diversification. Collectively, these multilevel analyses will help answer long-standing evolutionary questions about the diversity and turnover of sex determining systems in eukaryotes, but will also provide unprecedented insights into the biology of an important but virtually unexplored eukaryotic supergroup.

Mots-clés : sexual systems evolution,sex chromosomes,sexual reproduction,mutants,genetics,multicellularity,chromatin regulation,evolutionary genomics