Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet AlloGPCR (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors in eukaryotes. They bind a wide range of ligands, such as neurotransmitters, hormones, lipids and many others. GPCRs are the target of more than 30% of the drugs currently on the market, addressing neuropsychiatric, cardiovascular, pulmonary and metabolic disorders, cancer, obesity and AIDS. The functional versatility of GPCRs cannot be explained by a simple two-state model of activation considering only an active and an inactive state, as these receptors are highly dynamic and can explore a wide range of conformations. Some receptors of the family can signal in the absence of ligand (basal activity), and despite GPCR have been largely studied in the past years, little is known about their signal transduction mechanism. Apart from ligands and signalling partners, the structure and function of GPCRs can be modulated by lipids. In this context, our research will be divided in two steps: delineating the role of lipids on GPCR conformational landscape at the molecular scale (Aim1) and exploring an additional allosteric factor in line with lipid composition, the homo- and hetero-receptor oligomerisation (Aim2). To that purpose, we will apply an integrated, multidisciplinary analysis, to characterize protein dynamics under physiological conditions, with the GPCR reconstituted in model lipid systems or living cells, and in the presence of ligands, signalling and regulatory partners. We will use conformational probes to investigate the effect of lipids and other GPCRs on receptor dynamics, and correlate these findings with functional properties such as agonist binding and G protein coupling.

Mots clés : g protein coupled receptors, lipids, membrane environment, allosteric modulation, conformational landscape, dynamics, pharmacology, fluorescence, single molecule techniques, deer

Participants :
- Université de Montpellier (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 246668.4 €
- Stanford University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet GPCR-MS (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

G-protein coupled receptors (GPCRs) are the largest family of membrane proteins. They are involved in transducing stimuli and are implicated in many diseases including cancer and Alzheimer’s disease. As a result, they are the target of ~40% of drugs on the market. Despite an extensive library of known binding partners, dynamics related to GPCR activation (and inactivation) are not fully understood. The proposal uses a hypothesis driven approach to address three interrelated objectives. Objective 1 aims to reveal the propensities for lipids to modulate ligand binding to GPCRs. Objective 2 seeks to understand the intra-molecular factors regulating GPCR and G-protein assembly and their connection with the lipid environment. Objective 3 targets GPCR assembly and binding in the context of a native membrane. This project will use fuse knowledge and tools from molecular biology (e.g. protein expression and mutation) and analytical chemistry (mass spectrometry (MS)) to facilitate a comprehensive understanding of the molecular environment governing GPCR dynamics and assembly. The results of this project will contribute to our understanding of the influence of lipids on conformational dynamics to inform efforts to better understand off-target drug effects and drug tolerance. This information could in turn reveal novel GPCR conformations that facilitate state-selective structure-based drug discovery, with great implications for human health and quality of life. This proposal aligns with goals of the Marie Skłowdowska-Curie Fellowship: I will diversify my professional profile, which has focused on fundamental MS in the US, by gaining new competences in molecular and structural biology in Europe and thereby expand my personal and professional network through international mobility. The host laboratory is at the forefront of MS in structural biology and provides an excellent multidisciplinary training environment.

Mots clés : membrane proteins

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet SQSig (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

G-protein coupled receptors (GPCRs) are transmembrane proteins that are used by cells to transmit information through their membranes; binding of a ligand to their extracellular region provokes a conformational change, initiating a biological process in the cytosol. Copying this type of signaling pathway, which is fundamental to cells and thus a key target in medicinal chemistry, is a fascinating challenge that could allow researchers to bypass endogenous signaling pathways in cells and lead to true synthetic biology. In this project we propose to exploit the self-assembly properties of squaramides (SQs) to create a relay of information through a bilayer membrane. Monomeric SQs self-assemble as head-to-tail aggregates, forming ribbons with all the SQs oriented in the same direction. We have designed a family of scaffolded oligo-SQ arrays that will form intramolecular hydrogen-bonded ribbons aligned in either one direction or the other. We hypothesize that inverting the directionality of the terminal SQ of the ribbon will initiate a domino effect that switches the orientation of the whole array. By functionalizing the terminal SQ of the oligo-SQ relay with a binding site and the opposite end with a spectroscopic reporter, followed by insertion in model membranes, we will show that binding of an external ligand to the terminal SQ switches the directionality of the entire SQ-ribbon and provokes a spectroscopic response from the reporter located at the other side of the membrane. Thus this system will act as a synthetic GPCR, able to transmit conformational information from one side of a bilayer membrane to the other. The action combines the experience of the researcher in the preparation and study of SQs with the expertise of the host group in the development of transmembrane devices. While the fellow will bring new knowledge in synthetic and supramolecular chemistry to the host group, he will acquire valuable experience in the analysis and biophysics of membranes.

Mots clés : biomimetics, transmembrane signalling, large unilamellar vesicles, artificial molecular devices, hydrogen bonds, squaramides, rigid rods

Participants :
- University of Manchester (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet GANGNET (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

GANGNET is a project motivated by two intertwined emergencies of contemporary EU urban landscape: (1) the emergence of stable co-offending groups (2) the rapid propagation of inter-group violence (e.g. “knife epidemics” in UK). The key of my research is the use of innovative techniques from network theory and computational methods to inform regulators with better gang-crime risk prediction and more effective containment strategies. Relational networks are recognized as drivers of individual’s criminal activity: criminal groups are both organizations as well as social environments. For members of co-offending groups, interaction is both at group-level and at inter-group level. At the current state of art, little is known about the channel by which inter-personal links affect inter-group dynamics and trigger systemic phenomena. Therefore, it is unclear what individual-level factors EU policy-makers should monitor to control systemic urgencies such as the outbreak of group violence epidemics or formation of criminal alliances. Regulators contain crime via offender or groups-focused devices. However, as offenders and groups act within endogenous networks, unintended consequences such as increased inter-gang instability and violence can emerge as the result of spurious containment attempts. The project uncovers the theoretical and empirical structure of gang dynamics by adopting a network perspective. The goal is to understand how individuals act upon the influence of a stratified social network and to what extent isolated behaviour from single individuals can trigger inter-group system-wide dynamics. The project is developed along three directions aiming to understand how: (1) interaction between incentive-driven offenders determine group-level activities (2) group-level activities can lead to systemically relevant phenomena that unfold through relational networks (3) develop synthetic metrics to measure effectiveness of individual or group based containment policies

Mots clés : criminal networks, epidemics on networks, predictive policing, gangs, violence, knife epidemics

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet GLOB-POP-NAT (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

GLOB-POP-NAT proposes a new study of the transnational links between emerging Hindu nationalism (Hindutva) and contemporary European fascism in the 1920s-30s. Comprehending Hindutva as a form of populist extremism, through examining these thinks the project aims at a better understanding of the transnational nature of the radical populist right in the interwar period; and through this it seeks a better understanding of the radical right in comparative and historical perspective, and of global fascism as a concept. This project speaks to areas of vital current concern for the European Union. It reflects the Horizon 2020 Work Programme’s response to the challenge of fostering ‘inclusive, innovative and reflective societies’, itself a response to the remarkable growth in populist movements in Europe and globally in recent years. It refers in particular to the European Union policy on 'Racism and Xenophobia’ under its strategic priority of Justice and Fundamental Rights. The relationship between Hindutva and fascism, which emerged at the same time, has been subject to recent work, not least because of its timeliness to India’s own politics, and rise to power of the Hindu Nationalist Bharatiya Janata Party (BJP) since 2014. But this work lacks a focus on the geographical and cultural area which gave birth to Hindutva: Maharashtra, its western Indian heartland, which gave rise to its major institutions and founding ideologues. GLOB-POP-NAT fills this major gap in knowledge exhibited in the current state-of-the-art, proposing a vernacular study to offer in-depth insights on this relationship in Hindutva’s birthplace for the first time, and which the Experienced Researcher is expertly placed to undertake. The project is also innovative in blending regional and linguistic expertise with an interdisciplinary study of other aspects of vernacular culture to form a totalizing, holistic understanding of its regional political culture in the 1920s-1930s.

Mots clés : populism, extremism, global fascism, hindu nationalism, transnational, radical right

Participants :
- University of Mumbai (Inde) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Ca' Foscari University of Venice (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 193758.96 €
- Netaji institute for asian studies (Inde) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet GT-GM1 (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

GM-gangliosidosis (OMIM #230500) is a rare, autosomal recessive, neurodegenerative Lysosomal Storage Disorder. It is caused by mutations in the GLB1 gene, encoding the lysosomal hydrolase β-galactosidase. Infantile GM1-gangliosidosis is characterized by neurodevelopmental delay, hypotonia, dysphagia, seizures and death by 3 years of life. Due to the rapid progression and severe nature of this disease, which involves storage of undegraded metabolites and secondary mechanisms of cell damage, correction requires a rapid and robust enzyme delivery to the whole central nervous system (CNS), possibly associated to reduction of local inflammation. Here we propose an ex vivo gene therapy (GT) strategy aimed at preventing or ameliorating the symptoms of the disease in the murine model. Multiple copies of GLB1, alone or in association with a neuroprotective factor, will be delivered ex vivo to hematopoietic stem/progenitor cells by lentiviral gene transfer to determine a sustained and robust expression of the therapeutic enzyme in the CNS of transplanted mice. Genetically modified HSPCs will be administered by a novel approach combining the conventional intravenous route with direct administration into the brain lateral ventricles, to anticipate the myeloid reconstitution in the brain and possibly the therapeutic effect. Our working hypothesis is that this optimized GT strategy could successfully control disease manifestations in the animal model. Moreover, a deep genome-wide genomics analysis will be performed on individual brain cells to elucidate the molecular mechanisms at the basis of the disease and mediating the therapeutic effect. The study will generate a proof of concept for a future clinical development of an efficacious ex vivo GT for infantile GM1-gangliosidosis and will inspire the development of therapies for other LSDs.

Mots clés : lysosomal storage disorders, gm1 gangliosidosis

Participants :
- University of Padua (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171473.28 €
Projet GROUNDHR (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

GROUNDHR investigates how the construction of intercultural dialogue can be advanced as a means of grounding universal human rights in different contexts of cultural diversity. Despite the theoretical consensus, after decades of debate, that universal human rights do not require uniformity, the integration of cultural diversity in human rights’ norms and practice remains hard to realize. This research sees the ‘intercultural interpretation of human rights’ as a way to anchor universal human rights’ norms in a dialogue with what de Sousa Santos calls ‘Epistemologies of the South’. These locally-grounded views are rooted in other forms of knowledge belonging to those groups systematically excluded and silenced by colonialism and capitalism. However, a huge knowledge gap concerning these other human rights views exits. Therefore, from a methodological point of view, this project demonstrates the richness of a bottom-up, empirically grounded research by focusing on the human rights of indigenous peoples in Latin America. GROUNDHR’ design is grounded in a legal anthropological comparative, Guatemala and Colombia, approach applying methodological triangulation in order to grasp the (inter)national and local legal perceptions. It examines the challenges of grounding indigenous epistemologies of the human right to water and the construction of intercultural dialogue through the prism of consultation processes on hydroelectric dams. In Latin America, the implementation gap regarding this right to prior consultation about large-scale development projects in indigenous territories stands high on the political agenda. On the applied level, GROUNDHR will build strong practice-based evidence about these consultation processes, providing a richer understanding of the overall research question. Its results will also be translated into policy recommendations drawing on lessons learned and best practices that will guide stakeholders in future consultations.

Mots clés : intercultural human rights, legal anthropology, indigenous peoples, latin america

Participants :
- University of Coimbra (Portugal) — Coordinator, beneficiary, Recherche, subvention : 148635.6 €
Projet GROWING (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

GROWING is a project dealing with the use of minimally invasive methods for roots monitoring, with the specific aim of improving water use in arboriculture, viticulture and agronomy. The aim of GROWING is to develop our capability of understanding, through measuring and modeling, the actions of the root system on water state and fluxes in the soil-plant-atmosphere system. This is particularly critical in areas of water scarcity, such as the Mediterranean region. GROWING is based upon three scientific pillars: (a) an advanced plant root phenotyping technology using geophysical methods, overcoming current limitation in imaging roots under field working conditions; (b) a coupled above and below-ground monitoring using geophysical, plant physiology and atmospheric measurements and (c) a data assimilation scheme that uses the data above to construct a hydrogeophysical model of water distribution in soil and exchanges with the atmosphere. The scientific developments above will then foster the design of new tools and services for arboriculture, viticulture and agronomy with the ambition to transfer innovative knowledge to stakeholders, farmers, and winemakers in particular. The ground breaking nature of GROWING lies in the pooling of human, technical, and data resources, in order to better understand the hydric stress and roots response under a range of soil and agricultural practices. In order to warrant effective dissemination of the project’s results, I will work both with academic partners, the university in Padua (UNIPD) and the Lawrence Berkeley National Lab (LBNL) during the outgoing phase, and with farmers and stakeholders thanks to private companies’ collaboration (FruitionSciences, Noble research institute). A two- way knowledge transfer is expected, with novel practical solutions to be developed in order to make non-invasive geophysical methods a state-of-the-art practice particularly in high-value crops.

Mots clés : applied geophysics, water, roots, viticulture, arboriculture, agronomy

Participants :
- University of California System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Padua (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 251002.56 €
Projet GAMINCLUSIVE (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

GamInclusive proposes a framework to guide professionals and enthusiasts in designing gameful Equity, Diversity and Inclusion (EDI) educational approaches that promote cognitive, behavioural, and attitudinal learning to mitigate implicit bias and empower individuals in reflecting, exercising and upholding each others’ rights. It aims to address the intersection between gameful approaches and EDI education and training areas, which is yet to mature on theoretical, empirical and practical levels, by: G1) systematically integrating research and applications while consolidating this interdisciplinary subject with ground theory; G2) quantitative and qualitatively analyse empirical outcomes of the designed gameful instructional materials, prototypes and web learning application with user testing and controlled experiment by comparing the interaction, pre/post-test and survey responses; and G3) defining a practical framework for gameful EDI educational strategies that raises awareness about social issues and engages behavioural and attitudinal changes, by triangulating theoretical and empirical evidence. The host institution and my skill sets are highly complementary and suit the needs of this ground-breaking research, in which I will transfer my software development knowledge (especially in gamified education settings), and the Tampere University will provide the experience on humanities, psychology, and sustainability. The innovative and career-building aspect of GamInclusive is a novel combination of humanities, psychology, education, and gameful technologies towards the betterment of social sustainability issues, as those from 2030 Sustainable Development Goals (e.g., #5: Gender equality, #10: Reduced inequalities, and #16: Peace, justice and strong institutions). Tackling inequalities and discrimination issues, GamInclusive potential for social change attracts the interest of academia, industries, NGO fighting discrimination and overall society.

Mots clés : game based learning, gamification, sustainability, social issues, equality, inclusivity, awareness, implicit bias, discrimination, prejudice

Participants :
- Tampere University (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 190680.96 €
Projet GlypStx (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Gastrointestinal infections have substantial impact in both the developing world and in Europe with 1.5 billion cases each year leading to approximately two million deaths each year, 760,000 of which are in children under five years old. Many of these deaths are caused by bacteria for example E. coli O157, that produces protein toxins, including shiga-like toxin (SLT). In the human body, the surfaces of living cells are covered in complex carbohydrate molecules. This “sugar coating” allows the cells to interact with viruses, bacteria, and toxins that have complementary protein receptors. The pentagonal shiga-like toxin produced by E. coli O157 bacteria can attach to five copies of a specific carbohydrate on the gut wall and enter cells lining the intestine. The result is bloody diarrhoea and the toxin entering the circulatory system to cause kidney failure. In this project, we will make protein-based inhibitors that can prevent this toxin from attaching to, and enter kidney cells. The inhibitors will be synthetic glycoproteins that have 5 copies of the target sugar attached at specific sites so that they can bind to all 5 of the toxin’s receptor sites simultaneously providing an extremely strong interaction to prevent the toxin from entering cells. During the project we will synthesise a series of glycopeptides and attach them to pentameric protein scaffolds using site specific chemical and enzymatic modification. We will evaluate the glycoproteins as inhibitors of toxin adhesion and cell entry using a variety of cell and biophysical assays. The optimized inhibitors will have potential as a new class of future biopharmaceuticals.

Mots clés : glycoprotein, bacterial toxin, multivalency, protein engineering, glycobiology, carbohydrate, glycopeptide

Participants :
- University of Leeds (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €