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

Gene regulation is one of the main drivers of a cell's fate and function, but current methods that infer genome-wide regulatory networks have problems with inferring causal and/or combinatorial interactions. Pooled single-cell screening technologies, such as those developed in the host lab, now provide a powerful alternative to regulatory network inference. However, as this technology matures, data analysis is now more and more becoming the rate-limiting step in inferring causal and combinatorial regulatory networks. In this project, I will develop a combined computational and experimental workflow to infer regulatory networks. At the computational side, I will develop an algorithm that models how combinations of transcription factors affect a cell's state. The model will go beyond a ball-stick model, and investigate combinatorial logic, dosage effects, cell proliferation and cellular heterogeneity. The algorithm will also propose new combinations that may move a cell towards a fate of interest. Through multiple rounds of modelling and experimentation, I will iteratively improve our understanding of the causality and combinatorics of a regulatory network. I will validate the workflow on mesenchymal stem cells (MSCs), a cell type for which some (combinations of) transcription factors that drive its differentiation are already known, but for which a combinatorial view across lineages is still missing. I will first start with easier well-studied systems, such as adipocyte differentiation, and later in the project move on to less-studied systems such as adipocyte progenitors. By integrating experimental and computational techniques, the proposed project will provide a causal regulatory network across MSC lineages, and yield a framework to generate such a network in other systems. Moreover, the project will allow me to expand my computational skill set with emerging experimental techniques and management skills which will be invaluable for advancing my scientific career.


Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €
Projet SUPRO-GEN (Horizon 2020, appel à projets 2020)
Action : Staff Exchanges
Panel : Chemistry
Statut du projet : SIGNED

Gene therapy, most commonly using viral vectors, can be applied to inhibit or edit the expression of any gene of interest, being highly specific. However, there is an urgent need to find non-viral vectors with low toxicity and high transfection and targeting efficacies. The SUPRO-GEN project aims to design supramolecular vectors for gene delivery for applications in immunotherapy and cancer stem cell therapy. Peptide and glyco engineering of the vectors will result in high tumor targeting efficacy. Transfection and therapeutic efficacy will be tested in vitro and in vivo. Cell trafficking and biological fate of vectors will be studied by advanced imaging techniques. SUPRO-GEN is a concerted action based on multidisciplinary expertise in materials science, chemistry, genetic engineering, cancer biology, cancer therapy, and imaging. The project will bring together a talented consortium of academic groups and a high-tech SME from Spain, Italy, Israel, the United States, South Africa, Argentina and Thailand. Early Stage and Experienced researchers will receive training and conduct research in a hosting institution abroad. In addition to achieving the scientific goals, the project also aims to develop highly skilled professionals at the interface of materials science and engineering and the biological sciences.

Mots clés : self assembly, polyamines, gene therapy, silencing rna, gene editing, targeting peptides, carbohydrates, cancer stem cells, biological fate

Participants :
- University of Florence (Italie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 179400.0 €
- University of KwaZulu-Natal (Afrique du Sud) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- The University of Texas System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- The University of Tokyo (Japon) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Technion – Israel Institute of Technology (Israël) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 239200.0 €
- Nanovector srl (Italie) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 0.0 €
- Chulalongkorn University (Thaïlande) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Buenos Aires (Argentine) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- CIC biomaGUNE (Espagne) — Coordinator, beneficiary, Recherche, subvention : 570400.0 €
- Consejo Nacional de Investigaciones Científicas y Técnicas (Argentine) — Partner, organization partner, Recherche, subvention : 0.0 €
Projet GENERALIZED (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : CLOSED

Generalized geometry is a revolutionary approach to geometric structures pioneered by Hitchin in 2003, soon becoming an active topic catching the interest and bringing together the expertise of geometers and theoretical physicists. Generalized complex structures, defined for even-dimensional manifolds, are both a genuinely interesting mathematical structure, providing insight of complex and symplectic geometry, and the suitable notion for some physical theories like mirror symmetry. Odd-dimensional manifolds within generalized geometry have not been satisfactorily studied until the recent introduction of generalized geometry of type Bn and its study in my PhD thesis. There, the case of 3-manifolds drew special attention thanks to the recent Thurston's geometrization theorem and the fact that the type-change locus of a 3-manifold is a link, bringing in knot and link theory. This action combines the generalized geometry expertise of the experienced researcher with the host’s expertise on 3-manifold and knot and link theory in order to set a novel geometrical framework for structures on odd-dimensional manifolds, understand the case of 3-manifolds in depth, and create a two-way bridge between these previously unrelated areas, with innovative applications in both.

Mots clés : generalized, 3 manifolds, applications, knot, link, thurston, geometrization, complex, symplectic, k hler, structures, contact, sasakian, dirac, metric, character, variety, 4 manifold

Participants :
- Autonomous University of Barcelona (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 170121.6 €
Projet miRStem (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Generating Hematopoietic Stem Cells (HSCs) by Transcription Factor (TF) overexpression is of great interest in the stem cell field and promises considerable therapeutic potential. Among the systems described so far only one study, using murine B cells, has led to the generation of transplantable induced HSCs (iHSCs), although at exceedingly low efficiencies and using combinations between 6 and 8 TFs. We propose here a new approach to generate iHSCs based on the use of newly identified highly plastic “elite” type cells for reprogramming by the Yamanaka factors into induced pluripotent stem cells, generated by the transient exposure of B cells to C/EBPα. Hypothesizing that microRNAs could potentiate the effect of TFs in HSC reprogramming we will also analyze the effects of microRNA overexpression. For this we will first analyze HSCs and different hematopoietic progenitors to identify differentially expressed microRNAs. Different combinations of selected microRNAs will be cloned into inducible retroviral vectors together with hematopoietic TFs and used to infect “elite” CEBPα-primed B cells to screen for the induction, in vitro and in vivo, of iHSCs. The use of colony assays, cell surface marker and transcriptomic analyses of the resulting cells, as well as transplantation into irradiated mice, will enable us to identify microRNAs and TFs combinations that induce HSC reprogramming. The heterogeneity of iHSCs will then be tested by single cell expression analysis using RNA-seq. This project will provide new insights into the reprogramming of HSCs, the clinically most important type of adult stem cells, with potential medical applications. The proposed action will benefit the applicant’s career through acquisition of scientific maturity and independence.

Mots clés : transdifferentiation reprogramming hematopoietic stem cell microrna gene regulation

Participants :
- Centre for Genomic Regulation (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet ZPVMH (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Generating appropriate behavioural responses to sensory cues is crucial to ensure the survival of species, and relies on synaptic integration – the process by which individual neurons convert synaptic input into action potential output. How the brain performs the computations that produce specific behaviours is an essential question in Neuroscience and has direct relevance to human health and well-being. The aim of this project is to determine mechanisms of synaptic integration in a circuit underlying aggressive behaviour in the mouse, and analyse how single neurons in the ventromedial hypothalamic nucleus (VMH) contribute to computations leading to aggressive behaviour. By combining behavioural, genetic, electrophysiological and optical techniques, this project will determine: (i) the biophysical properties and local connectivity of VMH neurons, (ii) the anatomical localization of synaptic inputs along their dendritic tree, and (iii) how VMH neurons that drive aggressive behaviour integrate synaptic input from anatomically and molecularly-defined pathways. Recent in vitro studies have uncovered a previously unknown degree of complexity of information processing that single neurons can perform. While a lot of these studies combining electrophysiological, optical and computational approaches have focused on cortical circuits important for learned behaviours, innate behaviours have not benefited from such experimental and analysis framework. This project will become the first to implement such multidisciplinary approach to determine the mechanisms of synaptic integration in the hypothalamus. The results of this study will provide mechanisms of how VMH neurons generate patterns of activity that lead to aggression, which will advance our understanding of information processing in fundamental innate circuits and contribute to development of solutions for control of aggressive behaviour.

Mots clés : aggressive behaviour, hypothalamus, neuronal circuits, neuronal plasticity, synaptic integration, electrophysiology

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 53096.11 €
- UK Research and Innovation (Royaume-Uni) — Partner, beneficiary, Recherche, subvention : 142358.69 €
Projet GENMAINEVO (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Genome maintenance describes a subset of conserved cellular processes responsible for the faithful propagation of genomes across cell divisions. Defects in genome maintenance have been associated with several medical disorders such as cancer, aging and developmental defects. Recently we showed how perturbations in DNA replication, one of the most conserved processes in genome maintenance, induce an evolutionary process that leads to the sequential and concerted accumulation of adaptive mutations that increase the cellular fitness in response to replication stress. To what extent this fast-evolutionary rescue applies to other defects in genome maintenance, and what evolutionary trajectories are responsible for adaptation under different cellular stresses remain unexplored questions. Furthermore, while adaptive mutations rewire genetic networks to achieve increased fitness, their pleiotropic effect on cell biology is unknown. Here I propose a plan to comprehensively investigate these questions by taking advantage of a multi-disciplinary methodology using the budding yeast S. cerevisiae as a eukaryotic model organism. Experimental evolution of cells perturbed in several aspects of genome maintenance will be combined with computational and quantitative approaches to study their evolutionary adaptation in response to the different initial perturbations. Molecular genetics and cell biology techniques will be then used to investigate the consequence of these adaptations to cell’s sensitivity to genotoxic agents, a phenotype directly relevant for the treatment of medical-relevant diseases including cancer and infection diseases. The knowledge generated by the proposed research project will reveal important aspects of how cells adapt to genetic perturbations, with implications for both medical therapies and evolutionary cell biology at large.

Mots clés : experimental evolution, s  cerevisiae, drug resistance

Participants :
- Calouste Gulbenkian Foundation (Portugal) — Coordinator, beneficiary, Recherche, subvention : 147815.04 €
Projet INTERPLAY (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Genome-wide association studies (GWAS) for complex traits, including glycaemia, type 2 diabetes (T2D) and coronary heart disease (CHD) have been successful in identifying genetic variants associated with those phenotypes. However, they explained only a small proportion of the estimated heritability. Possible reasons include the interplay between genetics and lifestyle determinants, small-effect variants, structural variations and the difficult to characterize non-coding functional variants that interact with other genetic regions. This proposal, in a new era of precision medicine, englobes the systematic study of the interplay between genetic variants associated with glycaemia, T2D, CHD and dietary and lifestyle factors. We propose to conduct a comprehensive analysis of gene and gene-lifestyle interaction, including the existing international GWAS consortia of CARDIoGRAM, DIAGRAM, MAGIC, the U.S. based DPP clinical trial, and the European-wide networks of EPIC-InterAct and PREDIMED. We will test hypothesis about: 1) whether genetically driven hyperglycaemia increases risk of CHD, 2) the association between genetic determinants of CHD and intermediate metabolic phenotypes, and 3) whether dietary components and lifestyle changes influence these associations. Finally, we will extend and replicate these previous results in two independent populations, and to deploy a new method to identify implicated biological pathways. Information that will emerge from that project will provide valuable insights into missing heritability for T2D and CHD. Specifically we expect to uncover genetic determinants for faster CHD progression in T2D, identifying vulnerable individuals who are more likely to experience a differential response to current prevention strategies and to validate potential targets and avenues for intervention. The experienced researcher will emerged from the project with new skills, and the capability to launch his own research group in Europe.

Mots clés : gene diet interaction, type 2 diabetes, cardiovascular disease, lifestyle

Participants :
- The general hospital corporation (Etats-Unis) — Partner, organization partner, Autres, subvention : 0.0 €
- CERCA Institution (Espagne) — Coordinator, beneficiary, Recherche, subvention : 257191.2 €
Projet EvoSpa (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Given the looming antibiotic resistance crisis, it is imperative to understand the fundamental determinants of resistance evolution dynamics. When antibiotics are administered to a patient, imperfect drug penetration leads to a highly inhomogeneous concentration profile. In contrast, evolution experiments to study resistance are commonly performed in homogeneous liquid environments. Recently, there has been a surge of theoretical studies suggesting that spatial drug concentration gradients drastically accelerate resistance evolution as resistant mutants evade resource competition by invading drug-enriched territory. However, the effect of spatial structure on evolutionary dynamics remains unclear due to a lack of experimental assays with well-defined, inhomogeneous landscapes. Here, I propose to develop a novel experimental assay where bacteria migrate and evolve on a landscape consisting of hundreds of independently definable environments. This assay will be implemented using custom liquid handling and imaging robots to systematically program antibiotic landscapes and measure evolution on a wide range of drug environments. By combining this novel assay with theoretical modeling, I will investigate evolution in monotonous and rugged drug landscapes. Motivated by theoretical predictions that multi-drug strategies aimed at preventing resistance evolution become compromised in inhomogeneous environments, I will further investigate the effect of spatial inhomogeneity using defined multi-drug landscapes. This project will provide a unique, quantitative and systematic experimental investigation on how spatial structure affects evolutionary dynamics. Beyond bacteria evolving antibiotic resistance, the same concepts apply for tumor resistance evolution. Overall, this project will greatly advance our understanding of resistance evolution with broad biomedical implications.

Mots clés : experimental evolution, antibiotic resistance, theoretical modeling, robotic high throughput techniques

Participants :
- University of Cologne (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 174806.4 €
Projet EMoGrIS (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Glaciers and ice sheets contain distinct ecosystems and are very vulnerable to the ongoing climate change, with potentially significant impacts. However, predictions of future glacier ecosystem change are virtually impossible due to the lack of a theoretical framework of glacier and ice sheet ecosystems that would enable their mathematical modelling. The principal aims of the proposed fellowship are to provide a theoretical framework of the microbe-dominated supraglacial (glacier surface) ecosystem of the Greenland Ice Sheet and to develop a tool for prediction of the future change of the ecosystem, and to establish the Greenland Ice Sheet as a model ecosystem for studying microbial biogeography and diversity patterns. This will be achieved through developing a conceptual model of the system, its mathematical formulation, verification and validation, and subsequent simulations of future climatic scenarios. Furthermore, a sampling strategy will be developed allowing direct testing of relevant ecological hypotheses such as the diversity-productivity relationship. A two-way knowledge transfer is a key feature of this project: The Fellow will take advantage of the expertise of the Supervisor and the Department in ecological theory and modelling, while transferring his knowledge of glaciers as microbe-dominated ecosystems to the Department.

Mots clés : glacier ecosystem, ecological modelling, microbial ecology, greenland ice sheet

Participants :
- Charles University (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 142720.8 €
Projet EGRET (Horizon 2020, appel à projets 2014)
Action : Cofund Doctoral programme
Statut du projet : CLOSED

Glaucoma is the most common age-related neurodegenerative eye-disease in western society and one of the four major blinding eye diseases (cataract, macular degeneration, glaucoma, and diabetic retinopathy). Glaucoma is characterized by a progressive loss of retinal nerve cells. The early changes are often unnoticed by the patient. If untreated or detected too late, glaucoma will end up in blindness, yielding a profound loss of quality of life for the individual and major costs to society. In Europe, there are approximately 3 million people with glaucoma. They all need chronic medical care and, despite of that, approximately 15% of them will become blind during their lifetime. Increasing our knowledge on glaucoma and the aging visual system in general has tremendous potential for innovation in glaucoma care and can thus positively impact the future of millions of European citizens : 1) it enables the development of new tools for the early detection of glaucoma; 2) it can inspire the development and implementation of new treatments; 3) contributes to our understanding of the relationships between various neurodegenerative diseases, and 4) contributes to improving healthy aging in general. Given the vast complexity of the disease, we need researchers that are deeply knowledgeable about glaucoma and intimately familiar with the many different techniques required to study all aspects of glaucoma and the aging visual system: from functional test to anatomy, from gene to ganglion cell, from retina to brain. Generally, knowledge – and thus training – is fragmented and researchers that have been broadly trained are only scarcely – if not at all – available at present. To overcome this, EGRET – the European Glaucoma Research Training Program – will aim its efforts at teaching young researchers in how to acquire and apply new quantitative knowledge on the aging visual system in health and disease (specifically glaucoma).

Mots clés : glaucoma, ophthalmology, neuroscience, epidemiology, visual fields, eyes, brain, visual pathways

Participants :
- Abbott (Netherlands) (Pays-Bas) — Partner, organization partner, Organismes privés (hors enseignement), subvention : 0.0 €
- University Medical Center Groningen (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 1046400.0 €
- Amsterdam University Medical Centers (Pays-Bas) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Echodia (France) — Partner, organization partner, Organismes privés (hors enseignement), subvention : 0.0 €
- Australian National University (Australie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Stichting koninklijke visio, expertisecentrum voor slechtziende en blinde mensen (Pays-Bas) — Partner, organization partner, Autres, subvention : 0.0 €
- University of London (Royaume-Uni) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €