Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MASSIVE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
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 : 1276880.0 €

Multinational Enterprises (MNEs) are key ‘tectonic forces’, shaping the ‘mountains’ in a far-from-flat world economic geography. In 2010, MNEs generated value added for approximately US$16 trillion accounting for more than a quarter of world GDP (UNCTAD, 2012). The progessive expansion of firms from emerging economies into multinational enterprises is unprecedented. Outflows of FDIs from developing economies reached the record level of $426 billion in 2012, corresponding to 31% of global outflows, up from 16% in 2007 (UNCTAD, 2013). However, there is no consensus in the academic literature on both the factors able to shape the long-term location decisions of MNEs and, more generally, on the ultimate impact of MNEs on their host economies. This lack of consensus reflects three fundamental gaps in the existing literature. First the omission of some fundamental determinants of MNEs investment decisions in ‘traditional’ national-level analyses. Territorial/spatial factors, MNEs heterogeneity and local institutional conditions have been often overlooked in MNEs location analyses. Second the limited attention to the broader set of impacts of MNEs in their host economies and the role of institutional factors as selective ‘filters’ for these impacts. Third the intimate inter-connection between location motives and impacts has remained unexplored in the grey areas between separate streams of literature. This research project will investigate the location strategies of MNEs and their territorial impacts addressing these three fundamental gaps in the existing literature, shedding new light on the factors shaping the economic geography of MNEs and their impacts and providing policy-makers at all levels with new tools to promote innovation, employment and economic recovery after the current economic crisis.

Mots-clés : multinational enterprises,institutions,innovation,regions,european union
Projet ERC : IMPACT (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UZH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2492221.0 €

Multiple Sclerosis (MS) is a chronic inflammatory disease, where immune cell invasion into the central nervous system causes immunopathology and neurological deficit. Although disease-modifying therapies dramatically reduce disease activity, they hold the potential for severe adverse effects while long-term disability prospects remain poor. Moreover, there is to date no biomarker for monitoring the disease activity and to guide therapy decisions. I propose that the key to identifying such biomarkers is to combine single-cell mapping of leukocytes across well-curated patient cohorts with unbiased machine-learning based data interrogation. Using such an approach, we have already delineated a disease signature in a helper T cell population specific for MS. However, the immune compartment of cross-sectional cohorts is influenced by the individual genetic make up, which masks disease-specific signals and hinders a more precise characterisation of involved immune cell populations. To eliminate genetic influences, I here propose in aim 1 to interrogate the immune compartment of a unique cohort of monozygotic twin pairs -discordant for MS- and deeply analyse peripheral blood lymphocytes by single-cell mass cytometry, combined TcR and single cell sequencing, and epigenetic profiling. aim 2 to develop representation-learning methods to account for the paired genetics of twins or longitudinal samples and to include clinical covariates into the high-dimensional data set. aim 3 to use well-defined patient samples of MS-like disorders (MS-Mimics) and longitudinal samples of patients undergoing disease-modifying therapy (e.g. B cell depletion, autologous stem cell transplant) using single-cell mass cytometry. Ultimately, the goal is to reduce the dimensionality of disease signature(s) towards a clinically translatable low-dimensional biomarker that could be identified and quantified by routine methods available in the clinics.

Mots-clés : biomarker discovery,diagnosis,treatment response,multiple sclerosis,single cell analysis,machine learning
Projet ERC : GAMES (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1499946.0 €

Multiple Sclerosis (MS), an autoimmune demyelinating disease affecting the central nervous system (CNS), causes tremendous disability in young adults and inflicts huge economic burden on the society. The incidence of MS is steadily increasing in many countries arguing for environmental factors driven changes in disease induction. How and which environmental factors contribute to disease initiation and progression is unknown. Using a spontaneous mouse model of MS, we have shown that the gut microbiota is essential in triggering CNS autoimmunity. In contrast to the mice housed in conventional housing conditions, germ free (GF) mice, devoid of gut bacteria, were protected from spontaneous experimental autoimmune encephalomyelitis (sEAE). Re-colonization of GF mice with a complex regular gut flora derived from specific pathogen free (SPF) mice resulted in sEAE within 2-3 months. The re-colonization also triggered pro-inflammatory T and B cell responses. However, colonization of GF mice with a reduced gut flora failed to induce sEAE during our observation period suggesting a “specific” rather than a “broader” microbial trigger. In this proposal, I want to study the role of gut microbiota in CNS autoimmunity with the following aims: Aim 1: CNS autoimmunity triggering/protecting gut microbes and host immune responses I want to study how and which gut bacterial species are modulating CNS autoimmunity to better understand the origin of autoimmune responses and their relation to host immune responses. Aim 2: Molecular mechanisms of sensing of gut microbiota and microbial metabolites during CNS autoimmunity I want to identify the molecular pathways that are involved in sensing the gut microbiota and its metabolites which are relevant to CNS autoimmunity. Aim 3: Therapeutic application of gut microbiota for CNS autoimmunity I want to identify therapeutic strategies targeting gut microbiota to limit the development of inflammatory processes during CNS autoimmunity.

Mots-clés : gut microbiota,experimental autoimmune encephalomyelitis,multiple sclerosis
Projet ERC : multiBB (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Würzburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Multiple bonding between atoms is immensely important to chemistry, biology, physics and their associated industries; multiple bonds are both ubiquitous in everyday products and extremely useful functionalities for effecting chemical transformations. While very common with the elements carbon, nitrogen and oxygen, multiple bonding is in comparison extremely rare with other elements. Multiple bonding between heavier elements of the main group of the periodic table becomes less favourable the heavier the element becomes. However, this does not explain the relative paucity of multiple bonding with boron, which is immediately to carbon's left on the periodic table. In particular, isolable, stable compounds containing multiple bonds between two boron atoms are extremely rare, and until 2007 only a handful of charged examples existed. A revolution in this field has recently been witnessed with the syntheses of the first neutral compounds with boron-boron double bonds, diborenes, and the first compounds with boron-boron triple bonds, diborynes. The first neutral diborenes were prepared in 2007, however, we have recently developed a number of rational, selective and more general routes to these compounds. The first diboryne compounds were prepared by our group in 2012. The significance of these two families of molecules is not only their unusual multiple bonding but also the extremely high electron density on the boron atoms, an unusual situation for an element that is known for its electron-poor character. This high electron density leads to strong boron-based nucleophilicity and extremely high reduction potentials – both highly novel phenomena. This proposal aims to: (A) comprehensively explore the syntheses of these unique compounds and the limits thereof, and to (B) exploit the unusual reactivity of these electron-rich boron molecules in synthesis, small-molecule activation and materials science.

Mots-clés : main group chemistry,boron chemistry,inorganic synthesis,multiple bonds
Projet ERC : Phosphoprocessors (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Tartu — Pays : Estonie — Rôle : PI
Acronyme de l'entité : UT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999288.67 €

Multisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal in this application is to elucidate the molecular basis of this important mechanism. We recently demonstrated a novel phenomenon of multisite phosphorylation in cell cycle regulation. We showed that cyclin-dependent kinase (CDK)-dependent multisite phosphorylation of a crucial substrate is performed semiprocessively in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation networks along the disordered protein segments determine the net phosphorylation rate of the protein. This concept provides a new interpretation of CDK signal processing, and it can explain how the temporal order of cell cycle events is achieved. The goals of this study are: 1) We will seek proof of the model by rewiring the patterns of budding yeast Cdk1 multisite networks according to the rules we have identified, so to change the order of cell cycle events. Next, we will restore the order by alternative wiring of the same switches; 2) To apply the proposed model in the context of different kinases and complex substrate arrangements, we will study the Cdk1-dependent multisite phosphorylation of kinetochore components, to understand the phospho-regulation of kinetochore formation, microtubule attachment and error correction; 3) We will apply multisite phosphorylation to design circuits for synthetic biology. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field since the fast time scales and wide combinatorial possibilities.
Projet ERC : PROTEOFIT (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 1746825.0 €

Muscle function is essential for motion, exercise, and shivering, whereas physical inactivity is causally related to reduced metabolic fitness in animal models and humans. A critical requirement for muscle function is that proteins are properly produced and, if necessary, degraded to adapt the proteome to meet metabolic demands. However, there is a fundamental, open gap in understanding how challenges to muscle proteostasis are sensed and how protein fate is subsequently adapted to enhance muscle function in exercise or, conversely, how it is compromised in obesity. I hypothesize that protein fate is highly adaptive and can be fine-tuned to promote proteostasis, the integrity of muscle cells, and metabolic health. Identifying novel key regulators of these mechanisms in muscle may hold great therapeutic promise for targeting metabolic fitness to combat obesity and associated disorders. In this innovative project I want to define new mechanisms of muscle adaptation in humans and preclinical mouse models, with the ultimate goal of using this knowledge to improve muscle function and fitness in obesity. I will identify exercise- and obesity-specific substrates of the proteasome by ubiquitomics in human and mouse muscle and define how the ubiquitination and turnover of these proteins dictates muscle cell function. In a complementary approach, I will use novel loss- and gain-of-function mouse models allowing for precise muscle-specific manipulation of Nfe2l1, an adaptive regulator of proteasomal protein degradation, to define the biological and therapeutic significance of this pathway for muscle function in exercise and obesity. In summary, this novel work will provide a transformative molecular understanding of muscle adaption to metabolic challenges and provide insight into how this translates into metabolic fitness and the development of obesity and associated disorders in humans.

Mots-clés : muscle,exercise,obesity,metabolic adaptation,proteostasis,proteasome
Projet ERC : PrivatePieties (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Göttingen — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : GAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2494455.0 €

Muslim societies have been impacted since the 19th century by far-reaching processes of social and economic change as well as the development of an array of both Islamist and counter-Islamist movements. The present research project proposes to focus on Muslims whose ideas of piety are characterized by their private and individualistic character: they maintain that their piety is not subject to scrutiny by Islamist movements which value public religion as a means of societal control. Insistence on privacy (and individuality) may appear as rather a-political stance, yet, forms an eminently political position as it challenges claims to hegemony of interpretation of both established religious (and political) authorities as well as the leaders of Islamist movements. The present project asks which social and political consequences the movement towards private piety has and what private piety actually means for the social development of Muslim societies, for the development of Islamist movements and their ability to mobilize Muslims for political aims: what happens to politics in such a case? How do Islamist groups react that have to fear most from such a social movement? How also can we assess the role of women in patriarchal societies who appear to gain most from the move towards private piety? The project will approach these questions in the form of a comparative study of social and political contexts in Senegal, Tunisia, Egypt, Turkey, Iran and Pakistan as well as Muslim (Senegalese, Tunisian, Egyptian, etc.) diasporic communities in Europe. Our trans-regional comparative perspective will enable us to identify the social dynamics linked with the movement towards private piety and will be central to respond to the question whether such dynamics of change impact on processes of democratization in the countries chosen as case studies by our research group.

Mots-clés : islam,private pieties,social and political dynamics
Projet ERC : HEARTOFSTROKE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499450.0 €

My aim is to understand the cause of stroke in every single patient. Brain microinfarcts and macroinfarcts cause a major healthcare burden in Western societies both in terms of morbidity and costs. Cardiovascular thromboemboli from the heart, aorta and neck arteries are considered as the main cause. Still, the vast majority of brain infarcts are unexplained. In contrast to the thromboembolic explanation for brain infarcts, heart infarcts are known to be caused by local atherosclerotic plaque of the coronary arteries and impaired perfusion. This has led to successful preventive and therapeutic strategies against myocardial infarction. For brain infarcts, a blind eye is turned to local atherosclerotic plaque in the intracranial vasculature (Pipes) and impaired Perfusion as possible causes of macro and microinfarcts (Parenchyma). For the ‘3Ps’ (Pipes, Perfusion, Parenchyma) I have created new research fields based on innovative noninvasive arterial spin labeling perfusion MRI, perfusion reserve, perfusion territory and vessel wall MRI methods. In this project, I will go an important step beyond the state of the art by investigating the total intracranial burden of disease of these ‘3Ps’ and systematic evaluations in patients. Pipes: novel methods to visualise and characterise intracranial plaque including inflammatory plaque enhancement, intraplaque haemorrhage and calcification detection. Perfusion: novel methods to investigate hemodynamic impairment in areas with critically low perfusion with noninvasive arterial spin labeling MRI methods and perfusion reserve methods specific for each intracranial perfusion territory. Parenchyma: novel methods to detect microinfarcts. Technical innovations (Pipes, Perfusion) will be applied in synergy to explain micro and macroinfarcts (Parenchyma). Patient specific biomarkers will, similar to the heart, pave the way for designing preventive and therapeutic strategies aimed at reducing the burden of neurodegenerative diseases.

Mots-clés : stroke,cerebral blood flow,microinfarcts,circle of willis
Projet ERC : C18Signaling (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : German Cancer Research Center — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DKFZ
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

My lab studies how cells regulate their growth and metabolism during normal development and in disease. Recent work in my lab, published last year in Nature, identified the metabolite stearic acid (C18:0) as a novel regulator of mitochondrial function. We showed that dietary C18:0 acts via a novel signaling route whereby it covalently modifies the cell-surface Transferrin Receptor (TfR1) to regulate mitochondrial morphology. We found that modification of TfR1 by C18:0 ('stearoylation') is analogous to protein palmitoylation by C16:0 - it is a covalent thio-ester link and requires a transferase enzyme. This work made two conceptual contributions. 1) It uncovered a novel signaling route regulating mitochondrial function. 2) Relevant to this grant application, we found by mass spectrometry multiple other proteins that are stearoylated in mammalian cells. This thereby opens a new avenue of research, suggesting that C18:0 signals via several target proteins to regulate cellular growth and metabolism. I propose here to study this C18:0 signaling. To study C18:0 signaling we will exploit tools recently developed in my lab to 1) identify as complete a set as possible of proteins that are stearoylated in human and Drosophila cells, thereby characterizing the cellular 'stearylome', 2) study how stearoylation affects the molecular function of these target proteins, and thereby cellular growth and metabolism, and 3) study how stearoylation is added, and possibly removed, from target proteins. This work will change the way we view C18:0 from simply being a metabolite to being an important dietary signaling molecule that links nutritional uptake to cellular physiology. Via unknown mechanisms, dietary C18:0 is clinically known to have special properties for cardiovascular risk. Hence this proposal, discovering how C18:0 signals to regulate cells, will have implications for both normal development and for disease.

Mots-clés : drosophila
Projet ERC : CHIPIN (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Leibniz Association — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LG
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

My vision is to address a clinical problem with a novel and transformative approach. Using my unique expertise in cell biology, tissue engineering and translational research I will design technology platforms to test new treatments for human pancreatic cancer. Pancreatic tumours are cancers of unmet medical need with 85% of patients dying within 9 months of diagnosis. To find better therapies, we need patient-specific models that mimic the biology of tumour tissues and target interactions between malignant and non-malignant cells. Biomimetic tissue engineering is a powerful approach to generate 3D cancer models, however, only a few scientists use these technologies. Most 3D cultures of human cells include reconstituted matrices that originate from murine tumours containing undefined amounts of extracellular matrix and growth factors. There is no tissue-engineered 3D model that allows control over patient-specific and biomechanical characteristics of the pancreatic tumour microenvironment. I hypothesise that 3D approaches that replicate the native tissue composition and biomechanical properties will behave like real tumours to provide clinically predictive platforms and to test novel treatments that target both malignant and non-malignant cells. To test my hypothesis, I will: •3D-print matrix and cellular elements of the microenvironment of human pancreatic tumours •Develop a cancer-on-a-chip model of liver metastasis •Compare the crosstalk of malignant and other microenvironment components with the human disease •Validate my new platforms with treatments in clinical trials and test novel combination treatments that slow down or reduce tumour growth. In a multidisciplinary project, I will use: •3D printing to build platforms composed of hydrogels, fibrous scaffolds and patient-derived cells •Extracellular matrix molecules for chemical crosslinking into hydrogels •Cancer-on-a-chip models to study tumour metastasis •Imaging, biomechanical and multi-omics analyses.

Mots-clés : tumour microenvironment,pancreatic cancer,biomaterials,microfluidics,hydrogel,scaffold,patient derived cells