Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CorticALS (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université de Strasbourg — Pays : France — Rôle : Partner
Acronyme de l'entité : UNISTRA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset neurodegenerative disease of the motor system, with a prevalence of 2-3/100 000. In spite of intensive research efforts, ALS remains an incurable disease and presents with a very severe prognosis, leading to patient death within 2 to 5 years following diagnosis. At the cellular level, ALS is characterized by the combined degeneration of both upper motor neurons (UMN, or corticospinal motor neurons) whose cell bodies are located in the cerebral cortex, and that extend axons to the medulla and spinal cord, and lower motor neurons (LMN, or spinal motor neurons) whose cell bodies are located in the medulla and spinal cord, and that connect to the skeletal muscles. This dual impairment allows to discriminate ALS from other, less severe diseases affecting either UMN or LMN. Despite this precise clinical description, it is striking to note that preclinical studies have so far mostly concentrated on LMN, leaving aside the role of UMN in ALS. This project aims at shedding light on the contribution of the dysfunction and/or the loss of UMN in ALS, in order to design and test new therapeutic strategies based on the protection and/or the replacement of this exact neuronal type. This innovative question has never been directly asked so far. Our working hypothesis is that specific neurodegeneration of UMN, in the course of ALS, does not represent an isolated side effect, but rather actively contributes to the onset and progression of the disease. Based on the discovery of new molecular players, and the development of alternative therapies, this original thematic has the ambition to provide clinicians and patients with new answers and new therapeutic assets.

Mots-clés : amyotrophic lateral sclerosis,cortico spinal motorneurons,cell intrinsic and cell extrinsic mechanisms,endogenous neural stem cells programming,gene delivery,regenerative therapy
Projet ERC : DRUGSBUGS (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Swiss Tropical and Public Health Institute — Pays : Suisse — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2470621.0 €

An estimated 1.5 billion people are infected with soil-transmitted helminths (STHs) causing a global burden of 1.9 million disability-adjusted life years (DALYs). Current treatment options are limited. Preliminary studies in my lab hint towards a gut microbiome mechanism responsible for treatment failures of the most efficacious treatment currently available, albendazole-ivermectin. I propose an innovative 5-year project (“DRUGSBUGS”) that holds promise for major breakthroughs in anthelminthic drug discovery and development. I will deepen the understanding of current and potentially upcoming anthelminthics, in particular the microbiome-driven modulation of anthelminthic treatment. I will investigate underlying gut microbial structures in human stool samples associated with efficacy of albendazole-ivermectin treatment. Findings will be experimentally validated in vitro and in vivo. In addition, I speculate that emodepside will emerge as a novel key player in the anthelminthic drug armamentarium, which will enhance efficacy and reduce the risk of selection of resistant helminth populations. DRUGSBUGS proposes two Phase 2a dose selection trials with emodepside against Trichuris trichiura and hookworm in adults. Subsequent Phase 2b studies will assess whether emodepside is superior to albendazole against hookworm and T. trichiura. Using a microsampling technique, I will characterize the pharmacokinetics of emodepside in patients infected with T. trichiura and hookworm. In parallel, investing in innovative new technologies in the field of drug discovery will facilitate the discovery and development of the next generation of anthelminthics. I propose to study drug effects on motility and viability of different STH larvae applying electrical impedance spectroscopy on a microfluidic chip platform. My proposed research is of considerable public health relevance since it will ultimately result in improved treatments for soil-transmitted helminthiases.

Mots-clés : soil transmitted helminthiasis,hookworm,trichuris trichiura,pharmacomicrobiomics,emodepside
Projet ERC : NUHGD (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1229255.0 €

An important part of differentiable dynamics has been developed from the uniformly hyperbolic systems. These systems have been introduced by Smale in the 60's in order to address chaotic behavior and are now deeply understood from the qualitative, symbolic and statistic viewpoints. They correspond to the structurally stable dynamics. It appeared that large classes of non-hyperbolic systems also exist. Since the 80's, different notions of relaxed hyperbolicity have been introduced: non-uniformly hyperbolic measures, partial hyperbolicity,... They allowed to extend the previous approach to other families of systems and to handle new examples of dynamics: the fine description of the dynamics of Hénon maps for instance. The development of local perturbative technics have brought a rebirth for the qualitative description of generic systems. It also opened the door to describe more globally the spaces of differentiable dynamics. For instance, it allowed recent progresses towards the Palis conjecture which characterizes the absence of uniform hyperbolicity by the homoclinic bifurcations — homoclinic tangencies or heterodimensional cycles. We propose in the present project to develop technics for realizing more global perturbations, yielding a breakthrough in the subject. This would settle this conjecture for C1 diffeomorphisms and imply other classification results. These past years we have understood how qualitative dynamics of generic systems decompose into invariant pieces. We are now ready to describe more precisely the dynamics inside the pieces. We propose to combine these new geometrical ideas to the ergodic theory of non-uniformly hyperbolic systems. This will improve significantly our understanding of general smooth systems (for instance provide existence and finiteness of physical measures and measures of maximal entropy for new classes of systems beyond uniform hyperbolicity).

Mots-clés : smooth ergodic theory,partial hyperbolicity,non uniformly hyperbolic dynamics,generic dynamics
Projet ERC : RELAX-MAX (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 140000.0 €

Analytical methods are essential in many industries, such as chemistry, energy, pharmaceutical, and in health services. These methods usually fall into one of two categories: they either identify molecules and their structures or determine the properties of a fluid or a solid. This project will introduce a game-changing method to industry: high-resolution relaxometry in NMR, a label-free method, which combines both approaches as it identifies molecules and characterizes their individual properties within a complex fluid. The main goal of this project is to open a new market for high-resolution relaxometry instrumentation and methods in industry and health services. We have developed innovative hardware, methods, and software for applications of high-resolution relaxometry in biophysics during our ERC StG project. Introducing high-resolution relaxometry to industry will vastly expand what is currently a small budding market for academic users. This project will be carried out with our long-term partner, Bruker Biospin, the world leader in NMR instrumentation. Our strategy is to (1) identify competition and sectors of industry and high-potential end users that will benefit from this ground-breaking method; (2) improve the relaxometry hardware; (3) collaborate with target companies, including initiated work within the chemistry/energy and the pharmaceutical sectors, as well as a laboratory with links to health services; (4) demonstrate the potential of high-resolution relaxometry (e.g. better characterization of raw materials, enhanced processes, or new information for medical diagnostics). This strategy will lay the ground for the commercial deployment of high-resolution relaxometry in industry and health services. Overall, this project will have significant economic impact: new markets for instrumentation and enhanced competitiveness for end users, as well as society benefits in human health with the modernization of diagnostics towards personalized medicine.

Mots-clés : analytical tools,chemical and energy industries,pharmaceutical industry,medical diagnostics
Projet ERC : AngioMature (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Heidelberg University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1275000.0 €

Angiogenesis research has focused on the sprouting of new capillaries. The mechanisms of vessel maturation are much less well understood. Yet, the maintenance of a mature, quiescent, and organotypically-differentiated layer of endothelial cells (ECs) lining the inside of all blood vessels is vital for human health. The goal of ANGIOMATURE is to identify, validate, and implement novel mechanisms of vascular maturation and organotypic EC differentiation that are active during development, maintenance of vascular stability in adults, and undergo changes in aging. We recently identified previously unrecognized gene expression signatures of vascular maturation in a genome-wide screen of ECs isolated from newborn and adult mice. Epigenetic mechanisms were identified that control the EC transcriptome through gain and loss of DNA methylation as well as EC differentiation and signaling specification. These findings pave the way for groundbreaking novel opportunities to study vascular maturation. By characterizing functionally diverse types of blood vessels, including continuous ECs in lung and brain and sinusoidal ECs in liver and bone marrow, the ANGIOMATURE project will (1) determine up to single cell resolution the transcriptional and epigenetic program(s) of vascular maturation and organotypic differentiation during adolescence, (2) analyze the functional consequences of such program(s) in differentiated ECs and their adaptation to challenge, and (3) study changes of maturation and differentiation program(s) and vascular responses during aging. We will towards this end employ an interdisciplinary matrix of approaches involving omics, systems biology, conditional gene targeting, organoid cell culture, and experimental pathology to create a high-resolution structural and functional organotypic angioarchitectural map. The project will thereby yield transformative mechanistic insights into vital biological processes that are most important for human health and healthy aging.

Mots-clés : vascular biology,endothelial cell biology,vascular differentiation,organotypic vasculature,epigenetic regulation
Projet ERC : AngioMature (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : German Cancer Research Center — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : DKFZ
Type d'entité : Recherche
Financement ERC de l'entité : 1063918.0 €

Angiogenesis research has focused on the sprouting of new capillaries. The mechanisms of vessel maturation are much less well understood. Yet, the maintenance of a mature, quiescent, and organotypically-differentiated layer of endothelial cells (ECs) lining the inside of all blood vessels is vital for human health. The goal of ANGIOMATURE is to identify, validate, and implement novel mechanisms of vascular maturation and organotypic EC differentiation that are active during development, maintenance of vascular stability in adults, and undergo changes in aging. We recently identified previously unrecognized gene expression signatures of vascular maturation in a genome-wide screen of ECs isolated from newborn and adult mice. Epigenetic mechanisms were identified that control the EC transcriptome through gain and loss of DNA methylation as well as EC differentiation and signaling specification. These findings pave the way for groundbreaking novel opportunities to study vascular maturation. By characterizing functionally diverse types of blood vessels, including continuous ECs in lung and brain and sinusoidal ECs in liver and bone marrow, the ANGIOMATURE project will (1) determine up to single cell resolution the transcriptional and epigenetic program(s) of vascular maturation and organotypic differentiation during adolescence, (2) analyze the functional consequences of such program(s) in differentiated ECs and their adaptation to challenge, and (3) study changes of maturation and differentiation program(s) and vascular responses during aging. We will towards this end employ an interdisciplinary matrix of approaches involving omics, systems biology, conditional gene targeting, organoid cell culture, and experimental pathology to create a high-resolution structural and functional organotypic angioarchitectural map. The project will thereby yield transformative mechanistic insights into vital biological processes that are most important for human health and healthy aging.

Mots-clés : vascular biology,endothelial cell biology,vascular differentiation,organotypic vasculature,epigenetic regulation
Projet ERC : ALIVEAfrica (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Nairobi — Pays : Kenya — Rôle : Partner
Acronyme de l'entité : UON
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 97225.0 €

Animals are central to the livelihood strategies of millions of people in sub-Saharan Africa. Across the continent, animals provide sources of food and income, despite the growth of more diverse modes of subsistence. However, entanglements between humans and animals often have deeply problematic consequences for health, well-being and the environment. For example, unsustainable hunting practices reduce biodiversity and risk zoonotic disease transmission, and the uncontrolled use of antibiotics in intensified farming threatens to exacerbate anti-microbial resistance. Meanwhile, against a backdrop of climate-change induced pressures, development projects try to change human-animal relations in order to enhance productivity and economic resilience. Within this emerging dynamic it is important to reappraise the role of animals for contemporary livelihoods; the implications of human-animal relations for the wellbeing of multi-species communities; and the mechanisms of governance that seek to manage human-animal relations. This will be achieved through detailed ethnographic case studies in Kenya and Sierra Leone. This approach will shed light on contemporary livelihood strategies in sub-Saharan Africa. It will enable a major innovation in the social sciences by pushing forward new, post-human, visions for the fields of development and global health. Moreover, these local studies will be situated in a global context through a study of global assemblages of animal-focused development and One Health approaches. A deeper understanding of human-animal relationships has important implications for sustainability across species and will help to shift thinking around health and livelihoods in Africa from an anthropocentric perspective towards a post-humanist vision that enables multi-species stewardship. The project will co-produce knowledge with non-academic partners and build capacity among African scholars to maximise the reach of the research and ensure its long-term legacy.

Mots-clés : health,animals,livelihoods,one health,biomedicine,development,kenya,sierra leone,switzerland
Projet ERC : COLOUR PATTERN (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 319303.75 €

Animals display a tremendous diversity of patterns ‒from the colourful designs that adorn their body to repeated segmented appendages. Natural patterns result from the formation of discrete domains within developing tissues through the integration of positional cues by cells that consequently adopt specific fates and produce spatial heterogeneity. How can such developmental processes underlie the apparent complexity and diversity of natural patterns? We propose to address this long-standing question with an innovative experimental design: we will make use of natural variation as a powerful tool to facilitate the identification of patterning molecules and morphogenetic events. We will study colour pattern, a crucial adaptive trait that varies extensively in nature, from large colour domains to periodic designs. In amniotes, colour pattern is formed by spatial differences in the distribution of pigment cells and integumentary appendages. While the pigmentation system has been well characterized, the mechanisms governing the formation of compartments in the skin of wild animals have remained unclear, largely because laboratory models do not display ecologically-relevant colour patterns. We will use a combination of forward genetics, developmental biology, modelling, and imaging to study natural variation in the large colour domains of Estrildid finches and the periodic stripes of Galliform birds. For both phenotypes, we will characterize the organization of the embryonic skin and the mode of patterning (i.e., instructional patterning via external cues vs locally-occurring self-organization) underlying their formation, and identify the molecular factors and developmental processes contributing to their variation. Results from these studies will elucidate the biochemical events and tissue rearrangements orchestrating colour patterning in development and shed light on how these processes shape natural variation in this trait‒ and more generally, in natural patterns.
Projet ERC : CRCStemCellDynamics (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499875.0 €

Annually 1.2 million new cases of colorectal cancer (CRC) are seen worldwide and over 50% of patients die of the disease making it a leading cause of cancer-related mortality. A crucial contributing factor to these disappointing figures is that CRC is a heterogeneous disease and tumours differ extensively in the clinical presentation and response to therapy. Recent unsupervised classification studies highlight that only a proportion of this heterogeneity can be explained by the variation in commonly found (epi-)genetic aberrations. Hence the origins of CRC heterogeneity remain poorly understood. The central hypothesis of this research project is that the cell of origin contributes to the phenotype and functional properties of the pre-malignant clone and the resulting malignancy. To study this concept I will generate cell of origin- and mutation-specific molecular profiles of oncogenic clones and relate those to human CRC samples. Furthermore, I will quantitatively investigate how mutations and the cell of origin act in concert to determine the functional characteristics of the pre-malignant clone that ultimately develops into an invasive intestinal tumour. These studies are paralleled by the investigation of stem cell dynamics within established human CRCs by means of a novel marker independent lineage tracing strategy in combination with mathematical analysis techniques. This will provide critical and quantitative information on the relevance of the cancer stem cell concept in CRC and on the degree of inter-tumour variation with respect to the frequency and functional features of stem-like cells within individual CRCs and molecular subtypes of the disease. I am convinced that a better and quantitative understanding of the dynamical properties of stem cells during tumour development and within established CRCs will be pivotal for an improved classification, prevention and treatment of CRC.
Projet ERC : PeptIn (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Antibiotic resistance is increasing globally at such a pace that many experts fear the dawn of the post-antibiotic era if we fail to meet the urgent need for novel therapeutics. We evaluated if the working hypothesis of the MANGO ERC project that protein aggregation is driven by sequence specific interactions can be exploited to generate aggregates that are specifically toxic to bacteria without affecting mammalian cells. In particular we examined if peptides encoding aggregation-prone sequence segments of bacterial proteins can display antimicrobial activity by initiating aggregation in bacteria but not in mammalian cells. Unbiased in vitro screening of aggregating peptides lead to the identification of several hits that are strongly bactericidal against drug resistant gram+ S aureus strains, and others against pathogenic gram- E coli strains. The peptides cured mice from bacterial sepsis without apparent toxic side effects. The peptides enter and accumulate in the bacterial cytosol where they cause aggregation of bacterial polypeptides and the formation of inclusion bodies. Although the precise chain of events that leads to cell death remains to be elucidated, the ability to tap into aggregation-prone sequences of bacterial proteomes to elicit antimicrobial activity represents a rich and unexplored chemical space to be mined in search of novel therapeutic strategies to fight infectious diseases that are increasingly threatening global healthcare. However, given the novelty of this concept, the viability of aggregating peptides as antimicrobial therapeutics needs to be further advanced in order to consolidate the already significant interest from the pharmaceutical industry. In the current proposal we outline a series of experiments designed to address some of the key questions that were raised by potential investors and experts from the pharmaceutical sector to whom we presented the current data package.

Mots-clés : protein aggregation,antibacterials,antibiotics,antibiotic resistance