Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet SOCIOETHO (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Primatology provided extensive evidence of non-human primate behavior during conflicts claiming a behavioral universality shared with human primates. However, little is known about human behavior during conflicts because direct and undisturbed naturalistic observations of humans are rare. Recently, social scientists started to fill this gap by observing adult human behavior in real-life conflicts using Closed Circuits Television (CCTV). These systematic and unobtrusive observations of adult humans provided evidence for behavioral continuity between human and non-human primates during conflicts but currently lack integration with theories and methodologies from ethology. This project aims to connect ethology to the social sciences by testing theories of bystander conflict behavior from primatology on CCTV camera observations of human adults in 500 conflicts. It integrates methodological standards for observational studies from ethology in the social sciences, and provides motivational explanations of bystander actions in conflicts for the benefits of observational studies in both fields. The integrative methodology adds to both primatology, by providing understanding of human behavioral continuity in the primate order, and to sociology, by providing an evolutionary perspective on human behavior in the context of bystander conflict management. In turn, by conducting the project, I will acquire, as primatologist, an inclusive theoretical understanding of bystander interventions in primates, including the human species that will launch me into an interdisciplinary career.

Mots clés : homo sapiens, primates, conflict management, observational method

Participants :
- Dutch Research Council (Pays-Bas) — Coordinator, beneficiary, Recherche, subvention : 263358.72 €
Projet GENOLACT (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Probiotics are defined as live microorganisms with a long history of safe use and a robust evidence for providing beneficial effects to the consumer. The majority of probiotic bacteria belong to Lactobacillus genus, which includes a large number of GRAS species, essential in fermented food production and for use as food preservatives. Lactobacilli have also a range of non-food applications, such as industrial production of lactate for the textile industry in environmentally friendlier ways than chemical synthesis. Despite their broad use, health claims approval by EFSA for probiotics is challenging due to scientific difficulties in validating probiotic mechanisms and a lack of proper strain characterization. Although there has been a surge in research into probiotics, the conversion into actual claims and compliance with the regulatory requirements has proved difficult. The aim of the project is to perform forensically detailed comparative genomic analysis of Lactobacillus species to i) unravel the genetic backbone that has been moulded by genome decay and gene acquisition ii) delineate the genetic features and molecular mechanisms that underpin their health-promoting effects and suitability for use, and iii) identify genes associated with the phenotypes for new food applications. A deeper insight into the safety-related issues for food strains will provide a comprehensive assessment on risk factors to be transferred to companies as supplementary safety guidelines for successful health claim proposals. Data obtained will be used to develop new dietary solutions and safe non-food applications, thus increasing manufacturers’ interest in placing beneficial products on the market and meeting the consumer’s ambitions to live healthier. Within the project, the applicant will have the chance to perform high-level research with leading scientists and create a link between academic institutions and companies for efficient technology transfer and novel industrial solutions.

Mots clés : lactobacillus, comparative genomics, probiotics, health promoting effects, safety related issues

Participants :
- National University of Ireland (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187866.0 €
Projet HoloCellDeath (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Programmed cell death (PCD) is an essential function in multicellular organisms; it regulates normal development, responses to cell damage, and cell turnover. Accordingly, the PCD machinery present in the unicellular ancestors of animals was likely critical to the emergence of the complex multicellularity found in extant animals. However, we lack a full understanding of the PCD repertoire in the unicellular relatives of animals, and whether that ancestral repertoire underwent significant changes at the onset of Metazoa To fill this gap in our understanding we will perform a comparative genomics approach, combined with in vivo experiments, to examine the distribution and evolution of programmed cell death (PCD) proteins in the unicellular relatives of animals. This will identify which components of the PCD machinery were already present in the unicellular ancestor of animals, and the functional and regulatory changes that they might have undergone, and which led to the emergence of apoptosis in animals. Of particular interest is the subtype of PCD known as apoptosis, as the most characteristic apoptosis proteins are thought to be animal-specific. To investigate whether functional modifications occurred in the PCD repertoire at the origin of animals, we will perform in vivo experiments in two unicellular relatives of animals, Capsaspora and Creolimax, for which the host lab has developed transformation protocols. We will overexpress, and if possible silence, candidate pro- and anti-apoptotic proteins in those taxa to test whether they induce or protect against cell death. We will also examine protein interactions of these proteins during a proposed secondment. This project will provide the first comprehensive reconstruction of programmed cell death machinery across the group comprising animals and their unicellular relatives. The findings will be of interest not only to evolutionary biologists, but also to microbiologists, and to cell and developmental biologists.

Mots clés : eukaryotic evolution, holozoa, unicellular holozoans, protists

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet OPEN (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Project OPEN (Opening sub-ice shelf cavities and exploring their impact on dense water Production and Export in NEMO global ocean models) will work to improve our understanding of the role that the under ice shelf seas play in influencing Antarctic water mass characteristics and circulation. Currently none of the climate models used to inform the Intergovernmental Panel on Climate Change (IPCC) simulate sub-ice shelf cavities, thereby excluding the role of ice-ocean interactions in their reports. An essential piece of the puzzle is thus missing from the Earth system projections that are used to inform climate change adaptation and mitigation strategies. NEMO ocean model has recently developed the capacity to explicitly represent circulation under ice shelves, thereby enabling an investigation into the influence of introducing these key processes on global ocean circulation and hence climate. We hypothesise that the sub-ice shelf cavities have a major impact on dense water production and Antarctic Bottom Water (AABW) characteristics. AABW is the densest and deepest global water mass and constitutes the lower limb of the overturning circulation, transporting heat, carbon, oxygen and nutrients around our planet’s oceans. Given the vital role that AABW plays in ocean and climate regulation, obtaining a better understanding of the dynamics at its source region, and improving model capacity to simulate these processes is a scientific top priority. The recently developed NEMO configurations including sub-ice shelf cavities are the ideal tools for this investigation and we propose to utilize these to explore dense water production and export. Project OPEN will place a postdoctoral fellow with extensive observational expertise in a group of modelling experts at Sorbonne Université, thereby facilitating a mutually beneficial exchange of skills between the fellow and the host and enabling the timely advancement of this new field of ocean science.

Mots clés : southern ocean, water mass, circulation, ocean model, ice shelf, ice ocean interactions, meridional overturning circulation, climate

Participants :
- Sorbonne Université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196707.84 €
Projet LikelyStructures (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Proper understanding of the biological processes related to complex macromolecular entities depends on the detailed description of their 3D structures. For 100 years X-Ray Crystallography has been the main player in revealing high resolution structures. In the last decade, Bayesian statistics has yielded a breakthrough for solving challenging structures thanks to the integration of specialised error models essential to extract a weak signal from noisy data. Developed on such statistical methods, the program PHASER implements (along with experimental phasing) the Molecular Replacement technique in which the unknown phases, associated with the experimentally recorded intensities, are estimated from a homologous protein structure. Exploiting a deep new understanding of the link between model, data and phasing success, this technique will be decisively extended by the analysis of multiple models collected into ensembles optimised for likelihood calculations. Recent dramatic improvements in cryo-EM hardware have brought it into the high resolution realm and it is bound to become the main structural technique for the kind of challenging structures at the forefront. The leap from qualitative into quantitative Cryo-EM has already involved algorithmic approaches based on Maximum Likelihood. Generalising its full potential requires new methods that will lead to higher resolution reconstructions. The proposed integration of all sources of error is imperative for difficult samples. In this project, advances in both X-ray crystallography and cryo-EM data-analysis methods are planned, focusing on transferring experience acquired over many years in the first field into the second. Central to this project, the personal development of the experienced researcher will broaden his field of expertise in structural biology through advanced statistics with the aim of preparing, mentoring and leading him to an independent future research career in the development of methods.

Mots clés : integrated structural biology, cryo electron microscopy, bayesian statistics, maximum likelihood

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet FeCHACT (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Proposed to break new ground quickly and to establish new frontiers in cutting-edge Csp3-H functionalization chemistry, this proposal focuses on the development and exploitation of iron catalysed carbene transfer towards saturated hydrocarbons, a vast and low cost feedstock for the synthesis of more valuable chemicals. By rational design and evaluation of low toxicity and low cost iron complexes equipped with different electronic and steric properties, new environmental benign and sustainable catalytic strategies will be instilled into this promising synthetic methodology. Extending beyond the confines of traditional precious metals catalysed carbene transference, new non-hazardous sources for these fragments, compared with the currently employed diazocompounds, will be designed and refined in sulfur ylide compounds and zinc carbenoid reagents. The project will benefit from the accumulated wealth of experience of the candidate Dr. Hernán-Gómez in synthesis, characterization and kinetic studies of highly reactive organometallic reagents, spanning from transition metals to main group elements. This will offer valuable mechanistic insights into the investigated processes, including unequivocal identification of the catalytic active species, key aspects to progress the proposed project. Additionally, through collaboration with supervisor Prof. Costas, an internationally recognised leader in the chemistry of iron compounds applied to organic synthesis, Dr. Hernán-Gómez will be provided with the required support to successfully push forwards the frontiers of the proposed research line in the field of iron chemistry, a stepping stone towards achieving a senior academic position.

Mots clés : iron chemistry, carbenes, alkanes functionalization, catalysis, kinetics, x ray characterization

Participants :
- University of Girona (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 170121.6 €
Projet PDX-PC (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Prostate cancer (PC) is among the top five leading malignancies causing cancer mortality worldwide. Increased prevalence and declined mortality rate have led to an increment in follow-ups with a significant rise in the economic burden. In the last few years, several new options for metastatic disease have been approved leading to clinicians to have multiple choices of therapy sequences. However, not all patients initially respond and most of them eventually develop resistance. The ability of tumour cells to reprogram themselves and survive despite the blocked targets (tumour cell plasticity) may accounts for the absence of durable responses. In addition, the fact that initial treatments may affect the potential benefit of subsequent treatments highlights the need to discover predictive biomarkers for optimal treatment selection, allowing early changes in treatment for non-responding patients. This multidisciplinary project aims to elucidate the molecular mechanisms responsible for tumour cell plasticity associated to treatment response in metastatic PC. Patient-derived xenografts (PDX) in vivo models will be used, since they preserve molecular heterogeneity and therapeutic response observed in the clinic. They will be treated under different regimens. Tumour tissues will be analysed by RNA sequencing before and after treatment. Bioinformatics analysis will be used to establish molecular signatures of treatment response that will be validated in liquid biopsy (circulating tumour cells and cell free DNA) from metastatic PC patients undergoing different treatments. PDX-PC will provide a better understanding of the molecular evolution of the disease that will contribute to design more specific and individualized treatments. In the setting of non-curative therapy, the implementation of such molecular findings at clinical practice may help to guide treatment decisions, improve outcomes, and prevent unnecessary side effects and costly therapies in men with metastatic PC.

Mots clés : metastatic prostate cancer, treatment resistance, tumour cell plasticity

Participants :
- Fundació Clínic per a la Recerca Biomèdica (Espagne) — Coordinator, beneficiary, Recherche, subvention : 166202.88 €
- Monash University (Australie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet MPA-ND (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protein aggregation is associated with some of the most prevalent and devastating neurodegenerative disorders in our society, including Alzheimer’s and Parkinson’s diseases. The intricate details of the aggregation process are now beginning to emerge through major efforts for characterizing the associated protein deposits . However, knowledge about the aggregation of membrane proteins, which account for about one third of the human genome , is still almost completely missing despite increasing evidence that implicates in particular the aggregation of those in the respiratory chain and glucose metabolism in pathological pathways. To cover this huge gap, this project is aimed at elucidating the association of membrane protein aggregation with neurodegenerative diseases. The extensive biophysical investigation of the aggregates of two model sugar transporter proteins, galactose (GalP) and lactose (LacY) permeases, is proposed. Initially, controlled ways to promote the aggregation of these two proteins will be investigated in detail. The use of a range of biophysical spectroscopic methods is proposed to obtain information on the nature of the aggregates and their formation process. Further in vivo experiments will probe bacterial ageing in the presence of these aggregates. This work is expected to lead to new insights into the nature of membrane protein aggregates, characterization of their formation, and determination of their possible roles in neurodegenerative processes.

Mots clés : membrane proteins, protein misfolding, aggregation mechanism, biophysical characterization, neurodegenerative diseases

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet SHAPPI (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protein-protein interactions (PPIs) control all cellular processes relevant to health and disease, hence an outstanding challenge in chemical biology is to develop generic approaches for PPI inhibition. Such inhibitors (or chemical probes) represent unique tools to understand biological processes and starting points for drug discovery, for treatment of multiple illnesses for which effective treatments don’t currently exist e.g. cancer. SHAPPI will allow Zsofia Hegedus (the fellow) to join the laboratory of Andrew Wilson (host supervisor) at the University of Leeds (Host) and develop research expertise in the area of inhibiting protein-protein interactions. In doing so, she will (a) enhance her prospects to become an independent academic group leader and (b) address the need to train researchers in this key area of chemical biology and (c) develop cutting edge methods that advance peptidomimetic approaches for inhibition of protein-protein interactions. Scaffold hybridization will allow the combination of molecular scaffolds capable of hot spot mimicry with molecules that influence selectivity or potency. In combination with reversible chemistry this will allow generation of dynamic combinatorial libraries of rapid identification of selective and potent inhibitors. The fellowship will explore proteomimetic-peptide conjugates and peptide-small molecule dynamic combinatorial libraries to accelerate development of selective PPI inhibitors using two model interactions; HIF-1α/p300 and BID/BAX, both of which represent important targets for anticancer therapy.

Mots clés : dynamic covalent chemistry, peptidomimetics, protein protein interaction inhibitors

Participants :
- University of Leeds (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet EnLaCES (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Proteins are dynamic entities that undergo many structural transitions and fluctuations, which are essential to their biological functions. We, therefore, need continuous descriptions of protein conformational space in the form of energy landscapes in order to properly understand their mechanisms of action. This is now becoming possible through the use of hybrid methods, which combine computational biophysics with experimental structural biology and overcome the limitations of either approach alone. In this proposal, we present a new hybrid methodology that leverages recent innovations in cryo-electron microscopy image analysis to examine continuous dynamics and free energy landscapes of large, multi-domain proteins, which are not achievable with existing methods. Our novel interdisciplinary pipeline will involve the use of efficient coarse-grained representations of proteins from computational biophysics coupled with sophisticated image processing tools including 3D reconstruction, classification, and dimensionality reduction. The specific objective is to extract reaction coordinates from 3D class averages and use them to generate conformational landscapes onto which the raw 2D images can be mapped. The resulting free energy landscapes will reveal all conformational states with physiological relevance and the preferred transition pathways, which can be analysed further using molecular dynamics simulations. We will apply our pipeline to ionotropic glutamate receptors, which are tetrameric ligand-gated ion channels with large, dynamic, multi-domain architectures that are critical to synaptic transmission and plasticity in the mammalian central nervous system. We expect our results to be of great benefit to the broad structural biology community and to be instrumental in understanding brain physiology and designing treatments for a wide range of diseases.

Mots clés : cryo electron microscopy, continuous heterogeneity, molecular dynamics, ionotropic glutamate receptors

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €