Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : EvoGutHealth (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999085.0 €

The gut is a highly dynamic microbial ecosystem that controls human health through its collective metabolic activities. Microbial communities form metabolic networks that are essential for dietary breakdown, production of bioactive metabolites and resistance to infections. Bacterial lineages making up these networks evolve rapidly to adapt to the microbial, metabolic and immune environment of the gut. The lack of suitable model systems has limited our current understanding of the relevance of microbial community evolution in the gut and its impact on microbe-host mutualism. EvoGutHealth aims to fill this gap in knowledge by using an innovative, tuneable oligo-microbial model system that allows the study of how a native bacterial consortium evolves in its autochthonous host. Based on our preliminary data, we hypothesize that adaptive evolution shapes synergistic metabolic interactions between individual community members and this eventually affects global microbiome functions such as colonization resistance against pathogens. EvoGutHealth pursues three research goals: First, to identify environmental and host factors that shape the genetic potential of microbial communities in the gut. Second, to uncover how microbial community evolution influences disease-relevant microbiome features and metabolic pathways. Third, to model bacterial metabolic networks and elucidate how they are affected by the genetic alterations of their components. This combined work will fundamentally advance our understanding of the driving forces underlying metabolic network evolution in the mammalian gut. Moreover, it will illuminate how this evolution translates into functional changes. Finally, EvoGutHealth will provide necessary insight to develop strategies to steer microbial communities towards beneficial interactions promoting human health.

Mots-clés : gut microbiome,gnotobiotic mouse model,colonization resistance
Projet ERC : BIOCARD (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2285625.0 €

The heart is one of the first and most complex organs formed during human embryogenesis. While its anatomy and physiology have been extensively studied over centuries, the normal development of human heart and dysregulation in disease still remain poorly understood at the molecular/cellular level. Stem cell technologies hold promise for modelling development, analysing disease mechanisms, and developing potential therapies. By combining multidisciplinary approaches centred on human induced pluripotent stem cells (hiPSCs), BIOCARD aims at decoding the cellular and molecular principles of human cardiogenesis and developing advanced inter-chimeric human-pig models of cardiac development and disease. State-of-the-art genetic modification techniques and functional genomics will be used to establish a molecular atlas of cell type intermediates of human cardiogenesis in vitro and unravel how their proliferation, differentiation and lineage choice are regulated in health and disease. This in vitro approach will be complemented by detailed analyses of how distinct hiPSC-derived cardiac progenitor populations commit and contribute to specific cardiac compartments in interspecies chimeric hearts in vivo. Finally, we will capitalize on the novel concept that combinations of different well-defined hiPSC-derived cardiac progenitor pools with timely-matched, native extracellular matrix from embryonic hearts will accomplish for the first time the realization of human heart organoids as 3D culture systems of developing heart structures. Clearly, BIOCARD will open game-changing opportunities for devising novel biomedical applications, such as human heart chamber-specific disease modelling, large-scale drug testing in appropriate human 3D cardiac bio-mimics, and regenerative cell therapies based on functional ventricular-muscle patches and direct cell conversion in vivo.
Projet ERC : Profile Infection (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

The herpesvirus human cytomegalovirus (HCMV) infects the majority of the world's population, leading to severe diseases in millions of newborns and immunocompromised adults annually. During infection, HCMV extensively manipulates cellular gene expression to maintain conditions favorable for efficient viral propagation. Identifying the pathways that the virus relies on or subverts is of great interest as they have the potential to provide new therapeutic windows and reveal novel principles in cell biology. Over the past years high-throughput analyses have profoundly broadened our understanding of the processes that occur during HCMV infection. However, much of this analysis is focused on transcriptional changes at the lytic phase of infection leaving posttranscriptional regulation and the latent phase of the virus relatively untouched. Novel emerging technologies have the potential to extend our knowledge in areas that were heretofore unattainable. My overall goal is to decipher the multiple mechanisms by which HCMV modulates the host cell. For this, I will use multiple cutting-edge deep-sequencing and imaging technologies that will allow the analysis of novel aspects of host gene regulation during infection. Accordingly, the primary objectives of this research proposal are: 1) Deciphering posttranscriptional mechanisms that control cellular gene expression during HCMV infection; 2) Identifying and characterizing cellular protein diversification during infection; and 3) Uncovering the changes that occur in infected cells during latent infection. The knowledge generated from these objectives will provide us with a clearer depiction of the changes that take place during HCMV infection, which in turn can facilitate the development of novel anti-viral strategies. More broadly, with its comprehensive and complementarity approaches, this work will provide a paradigm for understanding how gene expression is regulated during a complex biological process.

Mots-clés : translation,cytomegalovirus,posttranscriptional regulation
Projet ERC : CONQR (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149998.0 €

The high number of cancer cases worldwide points to the large global demand for therapeutics for adenocarcinomas (the majority of lung, breast, and pancreatic cancers). Cancer metastases cause more than 90% of cancer patient deaths. There is thus great need to develop more targeted cancer therapies, as well as therapies that enhance the delivery and penetration of chemotherapies to reduce side effects and increase efficacy. A specific societal need is improved therapies for triple-negative breast cancer (TNBC), to which the targeted therapies developed for other breast cancers are not applicable. TNBC treatment, particularly for women with BRCA1 gene mutations, typically involves aggressive chemotherapy, mastectomy, and radiation treatment, with preventive oophorectomy also recommended. The physical and psychological impact of this regimen on young mothers and their families is unquantifiable, and the risk of relapse imposes continuing psychological stress. We have made a revolutionizing discovery that significantly controlled cancer cell adhesion, cell migration, primary tumor growth, and metastasis. We found that inhibition of the secreted enzyme QSOX1 by a monoclonal antibody inhibitor counteracts extracellular matrix ECM matrix stiffening and prevents tumor cell adhesion and migration. The QSOX1 inhibitor showed an added benefit in controlling primary tumor growth and metastasis when provided together with standard chemotherapy in a TNBC model in mice. The antibody drug we are developing based on these exciting discoveries has great promise for commercialization as a new therapeutic agent for TNBC and for other oncology indications. The goal of the CONQR project is to perform key preclinical experiments and explore market entering opportunities for commercialization of a novel QSOX1-inhibitory reagent against ECM remodeling in cancer. The intended outcome will be a development and commercialization plan to best position the product for out-licensing.

Mots-clés : commercialization,monoclonal antibody,qsox1 inhibitory reagent,therapeutics,adenocarcinoma,triple negative breast cancer,tnbc
Projet ERC : MRS in diabetes (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Maastricht University — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

The high prevalence of obesity-related metabolic disease such as diabetes and cardiovascular disease urgently requires earlier interventions in the pathogenesis of these diseases and the identification of new therapeutic targets that work in humans. To show the human relevance of mechanistic information gained from rodent and cell studies on the pathogenesis of insulin resistance and diabetes, human translational research is needed. Non-invasive techniques are key in human translational research. Magnetic Resonance Spectroscopy (MRS) is used in metabolic research, e.g. to determine ectopic lipids, but its potential is far from fully explored, and novel, dedicated MRS sequences can be developed to target new metabolites in vivo. As an example, I recently showed that the metabolite acetylcarnitine can be quantified by a modified MRS protocol, which allowed me to demonstrate in humans that acetylcarnitine concentrations in muscle strongly associate with insulin sensitivity. Furthermore, it lead to pilot data that show that the capacity to form acetylcarnitine can be hampered by low carnitine availability and that this is a determinant of metabolic flexibility, which can be succesfully targeted by carnitine supplementation. In the current proposal I aim to develop novel MRS methodology to detect levels of NAD+, another metabolite that is emerging from animal research as a central regulator of metabolic health. I will develop a non-invasive method to reliably quantify NAD+ in skeletal muscle by MRS. After careful validation of the method, I will determine the physiological relevance in a human cross-sectional study. I hypothesize that NAD+ and formation of acetylcarnitine act synergistically in determining protein acetylation and thereby affect metabolic flexibility. I will test this original hypothesis by increasing NAD+ and free carnitine using human interventional experiments and will investigate if this is a novel strategy to improve metabolic health.

Mots-clés : magnetic resonance spectrosopcy,insulin resistance,type 2 diabetes mellitus,metabolic flexibility,protein acetylation,nad
Projet ERC : ICY-LAB (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999885.0 €

The high-latitude regions are experiencing some of the most rapid changes observed in recent decades: polar temperatures are rising twice as fast as the global mean and there are concerns about the impact of sea-ice and glacier retreat on global oceans and climate. The high-latitude North Atlantic is also a key region for ecologically and economically important natural resources such as fisheries. How these resources will change in the future depends strongly on the response of marine biogeochemical cycling of essential nutrients to increasing anthropogenic stress. Diatoms are photosynthetic algae that are responsible for nearly half of the export of carbon from the sea surface to the seafloor, and they are a sensitive indication of the state of nutrient cycling. Diatoms are one of many organisms that precipitate biogenic opal, an amorphous glass made of silica (hydrated SiO2), to form protective skeletons, and one of the essential nutrients is therefore dissolved silicon (Si) in the form of silicic acid. The response of the silicon cycle to changing environmental conditions is critical for both carbon and nutrient cycling and it can now be addressed through high precision silicon isotopes, which is the focus of ICY-LAB. The approach will be to capture the whole silicon cycle system in areas of marked environmental change using careful field sampling strategies - with research expeditions to coastal Greenland and the open ocean Labrador Sea - coupled with cutting-edge analytical methods. The results will lead to an unprecedented and cross-disciplinary view of nutrient cycling, biomineralisation, and the taxonomy and biogeography of siliceous organisms in an ecologically important region of the North Atlantic. ICY-LAB is an exciting and novel project for which I am ideally placed to carry out, allowing me to develop a new method for looking at modern biogeochemical processes, adding to my existing palaeoclimate and biochemical expertise.
Projet ERC : HumAN (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1300458.76 €

The hippocampus is crucial for learning and memory and it hosts an extraordinary form of plasticity: the generation of new neurons throughout life, a process named adult hippocampal neurogenesis (AHN). Newly generated neurons grow in a specialised niche composed of unique vascular, glial, and neuronal elements. Impaired AHN leads to cognitive dysfunction and mood dysregulation in rodents. Recent work by my group reveals the persistence of AHN until the tenth decade of human life, as well as impairment of this process in patients with Alzheimer’s disease. The general aim of HumAN is to unveil the features that confer the human hippocampus with neurogenic potential, thoroughly characterising this niche in adulthood, physiological aging, and pathological conditions (AIM 1), and to identify potentially unique AHN signatures for specific neurodegenerative and psychiatric diseases (AIM 2). Moreover, we will determine, for the first time, whether new neurons integrate efficiently into the human hippocampus (AIM 3) and we will interrogate the subcellular machinery of these cells to unravel the mechanisms underlying AHN impairments in these diseases (AIM 4). The unprecedented quality of our collection of human hippocampal samples, obtained from 180 individuals (either controls or with specific neurodegenerative or psychiatric diseases), allows successful application of trail-blazing methodologies such as RNAscope, iterative indirect immunofluorescence imaging (4i)-microscopy, and super-resolution and stimulated emission depleted (STED) nano-resolution microscopy. HumAN will break new ground in the field of AHN by deepening our understanding not only of the mechanisms that control the maturation and synaptic integration of newly generated cells in human beings, but also of the pathophysiology of neurodegenerative and psychiatric diseases, thereby facilitating the identification of potential novel therapeutic targets for these as yet incurable conditions.

Mots-clés : adult hippocampal neurogenesis,human hippocampus,neurodegenerative diseases,neuronal maturation
Projet ERC : AFRAB (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499951.0 €

The historiography of Euro-American abolitionism is so vast that it has a history of its own (Brown 2006). By contrast, research on African abolitionism is a narrow field focused primarily on European anti-slavery activities. It presupposes that when Europe abolished slavery in Africa, Africans became abolitionists. This conclusion is unfounded. Many general questions have never been asked: When and where did African abolitionist movements develop? Who are the main ideologues of African abolitionism? How did abolitionism spread, among which groups? What forms of political struggle did African anti-slavery give rise to? While individual African abolitionists and regional movements have attracted limited attention, there is no major review of the phenomenon on a continental scale. AFRAB fills this gap. It contributes to African and global history and slavery studies by analyzing and comparing African abolitionist ideas and anti-slavery movements, the long-term consequences of European abolitionism, and the resilience of pro-slavery discourses.

Mots-clés : slavery,abolition,abolitionism,africa,colonialism,missions,ngos,activism,social movements,resistance
Projet ERC : PEGASUS (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : Partner
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

The horse provided us with rapid transportation, an almost unrivaled secondary product that tremendously impacted the politico-economical trajectory of our societies, revolutionizing the circulation of ideas, people, languages, religions and communication. Horse chariotry and cavalry also changed warfare and beyond the battlefield new equestrian technologies have stimulated agricultural productivity. However, the 5,500 year long history of horse domestication and management, which transformed the natural evolutionary trajectory of wild horses into the more than 625 domestic breeds living today, is difficult to reconstruct from archaeology, history and modern genetics alone. Yet, with archaeogenetics, one can access the genetic information from past individuals and track in great detail past population trajectories. In this project, I propose to build on the latest advances in the analysis of ancient DNA molecules to gather new genomic, epigenomic and metagenomic information from ancient horses. This will be integrated with archaeozoological, isotopic and historical data to enhance our understanding of the multiple processes underlying the transformation of the animal that perhaps most impacted our history. Starting from the characterization of pre-domestic populations of wild horses, I will evaluate the genomic and dietary impact of early domestication stages and will explore whether horses were independently domesticated in Iberia and the Pontic-Caspian steppe. I will follow how the emergence of chariotry and the development of heavy cavalry impacted the horse’s behavioural, physiological and biological makeup. I will reveal the horse characteristics that were preferred in various historical contexts and will investigate a diversity of management strategies and husbandry conditions to reveal their impact on horses, from classical and late antique periods until the recent creation of modern breeds by means of intensive selective breeding.

Mots-clés : ancient dna,horse domestication,animal management,animal husbandry,evolutionary genomics,diet,artificial selection,natural selection,biological adaptation
Projet ERC : ECOLANG (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Cologne — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 10149.76 €

The human brain has evolved the ability to support communication in complex and dynamic environments. In such environments, language is learned, and mostly used in face-to-face contexts in which processing and learning is based on multiple cues: linguistic (such as lexical, syntactic), but also discourse, prosody, face and hands (gestures). Yet, our understanding of how language is learnt and processed, and its associated neural circuitry, comes almost exclusively from reductionist approaches in which the multimodal signal is reduced to speech or text. ECOLANG will pioneer a new way to study language comprehension and learning using a real-world approach in which language is analysed in its rich face-to-face multimodal environment (i.e., language’s ecological niche). Experimental rigour is not compromised by the use of innovative technologies (combining automatic, manual and crowdsourcing methods for annotation; creating avatar stimuli for our experiments) and state-of-the-art modelling and data analysis (probabilistic modelling and network-based analyses). ECOLANG studies how the different cues available in face-to-face communication dynamically contribute to processing and learning in adults, children and aphasic patients in contexts representative of everyday conversation. We collect and annotate a corpus of naturalistic language which is then used to derive quantitative informativeness measures for each cue and their combination using computational models, tested and refined on the basis of behavioural and neuroscientific data. We use converging methodologies (behavioural, EEG, fMRI and lesion-symptom mapping) and we investigate different populations (3-4 years old children, healthy and aphasic adults) in order to develop mechanistic accounts of multimodal communication at the cognitive as well as neural level that can explain processing and learning (by both children and adults) and can have impact on the rehabilitation of language functions after stroke.

Mots-clés : neurobiology of language,gestures,face to face communication