Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet UNCERTHAIN (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cerebellar abnormalities are consistently reported in autism spectrum disorder patients, however the cerebellar contribution in the etiology of this pathophysiology remains poorly understood. It has been proposed that the cerebellum may drive the maturation and functionality of cortical high-order structures involved in the core symptoms of autism. However, the mechanisms by which the cerebellum could control these processes remain to be determined. The neural circuits linking cerebellum with the cerebral cortex via thalamic relay stations are the anatomical scaffolds underlying the cerebellar cognition. Recent data have shown that the thalamus plays a key role in the reorganization of cortical areas after early sensory deprivation. Therefore, during early development, abnormal cerebellar inputs to the thalamus may contribute to cortical dysfunctions that could lead in high-order deficits. However, despite being autism a neurodevelopmental disorder, any study has addressed the analysis of cerebello-thalamo-cortical circuits from a developmental perspective. The present project (UNCERTHAIN) offers an exceptional opportunity to shed light onto this issue as a result of the unique combination of approaches. Accordingly, we will use an experimental model that offers the possibility to embryonically alter the cerebellothalamic connectivity and thus, study the mechanisms underlying the events that influence the normal development and functioning of cortical circuits. Hence, we will adopt both multidisciplinary and innovative approaches to characterize the thalamocortical network in presence of a disrupted cerebellar input, the functional consequences and its relationship with autistic-like behaviors. The successful execution of this high-risk, high-impact research will provide insights on how the cerebellum governs the development of cortical areas essential for social and cognitive behaviors and its involvement in high-order neurodevelopmental disorders such as autism.

Mots clés : cerebellum, thalamus, autism

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet ONCOGENEVOL (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Certain papillomaviruses (PVs) are a major public health concern as in humans they are responsible for virtually all cases of cervical and anal cancer, and for a fraction of cancers on the penis, vagina, vulva and oropharynx. But oncogenic PVs are actually an unfortunate exception, as most PVs cause asymptomatic infections, and a few cause benign, wart-like lesions. Despite the efforts directed towards the understanding of the different clinical manifestations of infection, our knowledge on PV evolution remains fragmentary. Oncogenic human PVs arose recently, after acquiring the E5, E6 and E7 genes. The integration of the E5 proto-oncogene in the ancestral AlphaPV genome allowed viruses to evade host immune response. Thereafter E6 and E7 acquired the ability to target essential tumor suppressor proteins, paving the way for carcinogenesis. Tracking the evolutionary history of the E5, E6 and E7 oncogenes will thus help understand the emergence of oncogenic human PVs. Regarding the deep roots of PVs, small DNA viruses may share a common ancestor as they encode proteins sharing similar functions and domains, but their evolutionary origin is still an enigma. Here I propose to apply an evolutionary medicine approach, combining in silico and wet-lab approaches, to study key events that occurred during PV genome evolution. We will go back into history and study how and when certain PVs became oncogenic. We will resurrect the ancestral oncogenes, and experimentally test hypotheses about the function of the resurrected proteins in different environmental contexts. We will then generate a comprehensive scenario modelling the appearance of the modern PV genome and the emergence of the oncogenic phenotype of certain PVs. Finally we will explore the relationships between small DNA viruses and test whether they may have a common origin. Our ultimate aim is to understand why a few PVs are oncogenic for a few host species, while most PVs cause asymptomatic infections in most hosts.

Mots clés : ancestral gene resurrection, molecular dating, oncogenes, papillomaviruses, virus evolution, molecular evolution, cancer, cell virus interactions

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet CHAETA (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Chaetae, the chitinous bristles, of segmented worms are without a doubt one of their most characteristic features. A single cell, called chaetoblast, forms these complex extracellular structures, through an intricate interplay of the cytoskeleton and controlled polymerization of chitin. I have been investigating this fascinating system and published a series of papers describing the process of chaetal formation in various annelids using serial TEM and histology. With this proposed project I will combine my previous training and take the next logical step in the study of chaetogenesis; by investigating the molecular underpinnings of chaetal formation, focusing on chitin synthases. Chitin is one of the most dominant biopolymers in nature and a key building block of diverse extracellular structures. The bone eating worm Osedax japonicus will be the main focus of this study. Its fast and simple chaetal development, together with the drastic anatomical difference between males and females, renders it a perfect model to link the differential expression of chitin synthases to any relevant point of chaetogenesis that can be ultrastructurally profiled. Genetically well-examined annelid Capitella teleta will serve to test the functional genetics of chitin synthases using CRISPR/CAS9. This integrative approach combining advanced microscopical techniques with cutting-edge transcriptomics will result in a giant leap towards revealing the genetic network regulating chaetogenesis. I will be laying the groundwork to fully understand how morphologically complex, chitinous hard structures can be formed by a single cell. Elucidating the molecular and cellular mechanisms behind this process, that is comparable to a biological 3D printer, is highly relevant for not only annelid researchers but also to a broader scientific community studying biomechanics, biomineralization, cell-biology and even bionics.

Mots clés : organogenesis, chaetogenesis, morphogenesis, annelida, ultrastructure, chitin

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet PARTY (Horizon 2020, appel à projets 2014)
Action : Staff Exchanges
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Challenges faced by the marginalized youth in developing countries, such as unemployment, are not simple or easily solved. This is influenced by a number of factors including levels of education, gender, self-esteem, geographic location, physical ability and transport. The objective of the project is to contribute to solving the issues related to the youth unemployment in developing countries by creating participatory tools for human development that enable transformational change for the youth. Based on a service design approach, the project will provide tools for the marginalized youth suitable for daily use, enhancing regional democracy, increasing equal opportunities and contributing to human and service development with a particular target group: the San people in South Africa and Namibia. The San are faced with various social, cultural and political difficulties, and their communities are among the poorest in their countries, which are among the most unequal societies in the world. The tools aim to support the youth’s motivation and abilities to participate in the development of their own community towards a wider integration into their national socio-economic systems. The project focuses on the means and methods that assist in reaching the target group. Another objective is to cooperate with NGOs and other service providers in order to produce agile and human-centred processes and methods for developing service structures and systems towards improving the status of the marginalized youth. The third objective is to convey information on service design methods to those engaged in the development of youth services. The project aims to support the uptake of service design methods and tools in practical development work as well as the target and interest groups on a permanent basis. Thus the project establishes a strategy for continuation of the work with the target group and the local partners.

Mots clés : service design, research, youth, unemployment, employability, co creation, creative industries

Participants :
- Cape Peninsula University of Technology (Afrique du Sud) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Leeds (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 279000.0 €
- South African San Institute (Afrique du Sud) — Partner, organization partner, Autres, subvention : 0.0 €
- Incomindios switzerland (international committee for the indians of the americas) (Suisse) — Partner, organization partner, Autres, subvention : 0.0 €
- Paco design collaborative (Italie) — Partner, beneficiary, Autres, subvention : 283500.0 €
- University of Lapland (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 382500.0 €
- Namibia University of Science and Technology (Namibie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet CLIMGROWTH (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Changes in adult body size have become a flagship response to climate change. In organisms with a finite growth, as mammals and birds (higher vertebrates), it is thought to result foremost from climate-induced changes in growth trajectories (plasticity) rather than from changes in the frequency of alleles coding for body size (microevolution). As a key ecological trait, body size is also an important driver of individual life history: individual growth conditions will ultimately determine maturation, reproduction and ageing. However, to date no studies on higher vertebrates have formally investigated the contribution of developmental plasticity vs. microevolution at explaining changes in adult body size in response to climate change and, more importantly, no studies have tested for lifelong effects of climate-induced change in growth and size on individual life history within and between generations. In CLIMGROWTH, I propose to focus on the Alpine swift, a species of outstanding morphological and metabolic characteristics (non-stop flights of up to 200 days), for which preliminary results show a significant increase in body size. In particular, I will use an unprecedented long-term database (>4,000 individuals, >20 years) to combine complex, state-of-the-art, statistical modelling approaches in order to address these knowledge gaps by: (1) testing for the first time in a higher vertebrate the contribution of developmental plasticity and microevolution at accounting for a change in body size in response to climate change using pedigree-based quantitative genetic models; (2) providing long-awaited results on the lifelong consequences of natal climatic conditions on individual life histories, (3) their transgenerational effects on offspring life histories; and (4) addressing the debate between quantitative geneticists and demographers in how to generate reliable predictions for responses to climate change by applying the different approaches in the same study system.

Mots clés : evolutionary ecology, body size, climate change, growth, plasticity, microevolution, integrated population models, bird, wild

Participants :
- University of Aberdeen (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Ottawa (Canada) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Schweizerische vogelwarte sempach (Suisse) — Coordinator, beneficiary, Recherche, subvention : 209598.24 €
Projet LIIT-ChR2 (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Channelrhodopsins are type-I rhodopsin proteins found in green algae that function as sensory photoreceptors and turn into ion channels under illumination. Upon light absorbance, the retinal moiety induces a conformational change on the protein that opens a channel through which ions can pass. Neurons expressing channelrhodopsin-2 (ChR2) can be depolarized rapidly and reversibly by illumination, hence allowing control of the activation/inactivation of neurons in specific locations of the brain. For this reason, ChR2 has been used widely in optogenetics to study neuronal circuits and disorders in the brain, and to restore light sensitivity and visual capabilities in damaged retinas. However, in contrast to closely related bacteriorhodopsins or halorhodopsins, very little is known about their structure, light cycle and mechanism of action. The current structural evidences of ChR2 is limited to 1) the 6 Å projection map obtained by cryo-electron microscopy that contains a mixture of light (open channel) and dark (closed channel) states; and 2) the 2.3 Å X-ray structure of the dark state of a ChR1/ChR2 chimera. In the present proposal, we aim at elucidating the structure, properties and mechanism of action of the transient species of ChR2 during its photochemical cycle by means of theoretical methods and in close collaboration with the experimental biophysics groups of the host institute. The mechanisms of ion transport and channel opening will be simulated by enhanced sampling and free energy methods. Specific quantum-mechanics/molecular-mechanics (QM/MM) force matching force field will be generated ad hoc for the retinal moiety in the ChR2 environment. The model structures generated for the closed, open, and desensitized states will be validated 1) by comparison of the QM/MM spectroscopic properties of the model with experimental observations; and 2) by comparison to electron microscopy structures using a Bayesian analysis method recently developed in the host group.

Mots clés : molecular dynamics

Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €
Projet AlgSignSen (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : CLOSED

Chemical Reaction Network Theory (CRNT) focuses on determining the dynamical behavior of a (chemical) reaction network from its structural properties. To this end, different approaches within different areas of Mathematics are employed. We use here an algebraic geometric approach: The evolution of the concentrations of the species is modelled by a system of ordinary differential equations (ODEs). Under mass-action kinetics, the ODEs are polynomial, and thus the relevant steady states are the nonnegative solutions of a system of polynomial equations, which can be regarded as the nonnegative part of an algebraic variety (involving unknown parameters). This project addresses the problem of determining sign-sensitivities, that is, whether the concentration of one species at steady state increases/decreases after a perturbation is applied to the system. In particular, we wonder under which structural conditions are sign-sensitivities independent of the parameters of the system and of the original steady state. The novelty of this proposal resides in that we do not aim at developing algorithms for finding sign-sensitivities, but at obtaining theorems that explain why and when some sign-sensitivities are uniquely determined. The results will allow potential users to manipulate large networks without knowing all the parameters and overcomes the uncertainty of current algorithms arising from having to choose parameter values. I will use my background in Algebraic Geometry to begin a research career in Applied Algebraic Geometry. I will acquire new competences in interdisciplinary research and intersectorial transference of science, and improve my skills in communication and project management. I will work under the mentorship of Elisenda Feliu, in the group Mathematics of Reaction Networks. Due to their resources, experience and knowledge, they represent the perfect environment for the transition from Pure to Applied Mathematics, and in particular for my training in CRNT.

Mots clés : chemical reaction network theory, mass action, parametric polynomial equations, steady states, dsr graph, positive algebraic variety

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet CylcoRu4PACT (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Chemotherapy is efficient in curing cancer, but most treatments are very hard to stand for the patient, and side effects limit treatment efficacy. Phototherapy is a promising alternative, where the toxicity of a light-sensitive chemotherapeutic compound is locally released upon visible light irradiation of the compound-containing tumour. Photodynamic therapy is already available in the clinic for oxygen-rich tumours; however, it fails when the oxygen concentration at the place of irradiation is too low. In this project I propose to synthesize new ruthenium-based photochemotherapeutic compounds containing cyclometallated ligand, and to test them in an in vitro model of hypoxic cancer. The presence of a carbon-metal bond is known to shift the light absorption properties of ruthenium polypyridyl complexes towards the photodynamic window, a wavelength range where light penetrates optimally into biological tissues. However, cyclometallation usually quenches the ligand photosubstitution properties of ruthenium compounds because it strongly modifies the energy of their excited states. In this project, I will introduce sterically hindering groups on the cyclometallated ligand to recover photoreactivity of the complexes while keeping light absorption at high wavelengths. The challenges of this project consist on the one hand in achieving efficient ligand photosubstitution reactions with cyclometallated ruthenium compounds, and on the other hand in minimizing the cytotoxicity in the dark while maximizing cytotoxicity after red light irradiation at low oxygen concentrations. The ruthenium prodrugs will be synthesized, their photochemical properties will be measured, and their cytotoxicity against human cancer cell lines will be determined in an in vitro model of hypoxic cancer. This project will set new grounds in the treatment of hypoxic tumours and propose a new way to overcome side effects occurring in traditional anticancer chemotherapy.

Mots clés : ruthenium, cytotoxicity, chemotherapy, phototherapy

Participants :
- Leiden University (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165598.8 €
Projet CHIKV-FBDD (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Chikungunya virus (CHIKV) is a medically important pathogen that affected millions of people around the world. CHIKV infection causes high fever, intense joint pain and often leads to chronic virus-induced arthritis, thus there is a clear necessity to develop antiviral compounds capable of eliminating persisting virus. CHIKV is an alphavirus from Togaviridae family with single-stranded positive-sense RNA genome, which replication is carried out by a complex of four viral non-structural (ns) proteins, initially produced in a form of ns-polyprotein precursor and released by proteolytic processing. Because multifunctional nsP2 plays a central role in a replication cycle of CHIKV by exhibiting various enzymatic activities and counteracting cellular defence mechanisms, it represents the most attractive target for drug design and screening. Currently, the structural information regarding CHIKV ns-proteins is limited, whereas the platforms for in vitro testing the potential inhibitors are largely non-existent. Therefore the first aims of this project will be to apply structural biology approaches to elucidate spatial organization of nsP2 and to reveal its contacts with other ns-proteins in the replication complex. The druggability of nsP2 will be then explored by screening recombinant proteins against libraries of chemical fragments and characterizing binding of small molecules using sensitive biophysical techniques and crystallographic analysis. The potential of selected compounds to interfere with enzymatic or interaction properties of nsP2 will be revealed using variety of fluorescence-based assays developed in this project. The newly discovered knowledge about structural features of CHIKV nsP2, identification of novel protein surface pockets and binding molecules, and the development of functional assays for the analysis of their inhibitory potential are expected to create the ground for future elaboration of novel specific inhibitors of CHIKV.

Mots clés : chikungunya virus, viral replication, structural biology, protein protein interaction, fragment based drug discovery

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €