Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet GENOMEPEP (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The human genome is over 3 billion nucleotides long, yet only 1,5% of it codes for proteins. In recent years, a striking number of regions of the genome have been discovered to be capable of being transcribed and translated into short polypeptides. These micropeptides comprise of less than 100 amino acids and to date, more than 160 000 different micropeptides have been catalogued within human tissues. These protein products are hypothesized to participate in numerous molecular, cellular and physiological processes, yet the function of but a few micropeptides has been identified. Subsequently, due to its largely unknown functionality, the micropeptidome is commonly overlooked during genomic studies. Due to increasing life expectancy and detrimental lifestyle habits, the European population can be considered to be a high-risk population for cardiovascular diseases, which cause millions of deaths per annum, while taking a tremendous financial toll on the regional economy. GENOMEPEP aims to pinpoint novel micropeptides participating in the pathogenesis of cardiovascular diseases by investigating the genetic variation within the micropeptidome-encoding genome in correlation to existing common cardiovascular phenotypes in population. This will be achieved by establishing a computational analysis pipeline based on biometric, genotype and health records data available within the Estonian and Finnish biobanks. The identification of novel pathogenic genes and the development of guidelines to investigate the micropeptidome would assist in the advancement of research, diagnostic medicine and pharmacology both in public and private sectors. The results of GENOMEPEP will address the CVD research aspect highlighted in “Societal Challenge 1” work program of Horizon 2020, as well as improve other research priorities set by Horizon 2020, e.g. the progression of personalized medicine and support the decrease of economic burden by healthcare.

Mots clés : cardiovascular diseases, genome wide association studies, phenome wide association studies, micropeptides, small open reading frames  sorfs, bioinformatics, non coding genome, metabolomics

Participants :
- University of Tartu (Estonie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 213289.92 €
Projet EpiMethFly (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The identification of reversible m6A RNA modification strongly points towards the existence of a novel level of complexity of gene expression regulation. Recent studies have suggested that m6A might be involved in several biological processes and that dysregulation of this modification may contributes to neuro-developmental abnormalities and cancer. The aim of the described research is to clarify the role of m6A RNA modification in the nervous system in physiological conditions -during brain development - and to discover its contribution to pathological conditions - Glioblastoma. To achieve this goal I propose to use Drosophila melanogaster to study : Aim 1 the impact of perturbing different members of the m6A machinery on brain morphology, progenitors differentiation and neuronal axon growth and guidance; Aim2 the impact of modulating the levels of m6A RNA modification in a Glioblastoma model and study the effect of this perturbation on tumor growth and progression. The results obtained will be of fundamental importance for the development of the field of epitranscriptomics by shedding light on the biological outcome of m6A modification in-vivo. In particular, Drosophila might become an efficient model to screen for novel members of the m6A machinery and to clarify how m6A is read and translated into a biological response. Finally, the data obtained by the analysis of the Glioblastoma model, will strongly contribute to the understanding of the link between RNA methylation and tumor development and aggressiveness.

Mots clés : drosophila melanogaster, m6a rna methylation, axon guidance, brain wiring, glioblastoma

Participants :
- University of Trento (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 180277.2 €
Projet ISOMOD (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

The immensity of the oceans makes it difficult to monitor them at a spatio-temporal scale that is relevant for resolving ecological processes and responses to decades of pressure from multiple anthropological stressors. With IsoMod, I aim to map the biogeochemical tracers (stable isotope (SI) composition) at the base of the food web to inform three key measures of marine ecosystem processes that might be affected by these stressors: productivity, food web structure and animal migration pathways. The isoscapes will be developed at the scale of the North Atlantic Ocean and will be based on Calanus spp. carbon and nitrogen SI values, δ13C and δ15N. Lipid rich zooplankton organisms such as C. finmarchicus fuel a large part of the higher trophic level in the North Atlantic, including many species of fish, birds and mammals. I will use a recently developed spatial statistic approach where high resolution observational data (e.g., satellite data) are applied as predictors of SI variability, and apply these models to produce isoscapes with a full coverage of the study area. The application of these isoscapes will be showcased in two case studies. The first will test the role of changes in Atlantic puffin (Fratercula arctica) winter diet in key life-history parameters (e.g., body condition, survival rate). Specifically, the isoscapes will be used to provide the trophic baseline needed to investigate changes in puffin trophic position associated with changes in diet. The second case study will use prey SI to improve forecast of Northeast Atlantic mackerel (Scomber scombrus) summer distribution. Variation in SI values can be linked to variation in secondary productivity and this will be used to identify best foraging conditions for mackerel ahead of their migration to the summer feeding grounds. This information will be investigated as a driver of mackerel summer distribution and their recent shift in distribution.

Mots clés : stable isotopes, animal tracking, trophic baseline

Participants :
- UiT The Arctic University of Norway (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214158.72 €
Projet IMMUNETREH (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Statut du projet : CLOSED

The immune response is an energy demanding process and immune cells must have a privileged access to energy/nutrients. While in mammalian system, this privileged access is achieved for example by insulin-independent glucose transporter, how is it achieved in insect is not known. The host laboratory has obtained preliminary results suggesting that the privileged access of fruit fly immune cells to nutrients might be achieved by using trehalose instead of glucose. It is known for a very long time that the primary sugar in insect is trehalose but it is a completely new idea that this carbohydrate could actually play an important role in the privileged access of immunity to resources, as in one of the most fundamental evolutionary trait. The goal of this project is therefore to test if activated Drosophila immune cells preferentially uptake trehalose and convert it to glucose intracellularly, being thus independent of the systemic carbohydrate regulation, and how important would it be for an efficient immune response. The project is based on a multidisciplinary approaches, when tissue-specific genetic tools will be used to manipulate metabolism in vivo in order to study immune response using techniques of molecular biology, developmental biology and immunology and state-of-the-art metabolic approaches. The goal for the researcher is to learn how to use Drosophila genetics and the infection models, well established in the host laboratory, and combine them with her expertise in insect physiology, cell culture and especially metabolomics.

Mots clés : immunometabolism, drosophila, trehalose

Participants :
- University of South Bohemia in České Budějovice (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 156980.64 €
Projet OTULINVIVO (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The immune system is essential for host defense against infections. Methionine1-linked ‘linear’ ubiquitin chains (Met1-Ub) have emerged as a crucial activator of NF-κB transcription factors, which are vital to immune responses. Recent findings suggest that defects in Met1-Ub signaling in humans can lead to severe immune dysfunction and cancer. Met1-Ub is generated by the linear ubiquitin chain assembly complex (LUBAC). Yet, how LUBAC and Met1-Ub signaling are regulated remains elusive. We recently discovered OTULIN, the only deubiquitinase known to specifically disassemble Met1-Ub. OTULIN antagonizes LUBAC and restricts Met1-Ub and NF-κB signaling in cell culture; however, the role of OTULIN and Met1-Ub in immune signaling and host defense in vivo is largely unknown. We have established novel mouse strains with cell type-specific deletion of OTULIN. I will use these mice to explore the in vivo function of OTULIN and Met1-Ub in the innate and adaptive immune responses, and to identify OTULIN substrates in primary cells using state-of-the-art mass spectrometry-based proteomics. I will study OTULIN’s role in immune homeostasis, in response to bacterial infection, and in mounting type-1 and type-2 adaptive immune responses by state-of-the-art methods of immunological analyses including comprehensive multiplex analyses of cytokines. Met1-Ub regulates the acute phase cytokines TNF and IL-6 and may thus control the development of type-1 versus type-2 immune responses. Hence, I will test OTULIN’s role in models of asthma, a disorder characterized by an imbalance between type-1 and type-2 responses. Subsequently, I will analyze immune signaling pathways in primary cells using mass spectrometry-based proteomics to identify OTULIN substrates in specific cell types. This will greatly deepen our understanding of the physiological role of OTULIN and Met1-Ub in the immune response and may provide important insight into human immunological disorders and rationales to treat these.

Mots clés : ubiquitin, linear ubiquitin, atypical ubiquitin, met1 ubiquitin, deubiquitylating enzymes, ubiquitin signaling, prr signaling, inflammatory signaling, inflammation, mouse models

Participants :
- UK Research and Innovation (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 183454.8 €
Projet Stroma.Org (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The immune system is faced with a substantial challenge – it must provide rapid, tailored immunity to the host without a priori knowledge of when, where and which pathogen will invade, and at the same avoid damage to self. Recent evidence, including my own prior work, suggests that the anatomical organization of the lymphoid organ in which the immune response is initiated determines the quality and quantity of the response. Lymph nodes (LNs) are supported by a scaffold of mesenchyme-derived stromal cells (SCs) that not only provides gross anatomical support, but also produces critical survival factors and localization/movement guidance cues to antigen-presenting cells and antigen-responsive lymphocytes during the initiation of the immune response. Despite the now emerging role of SCs in immune responsiveness, it is unclear at a molecular and cellular level how these cells support the fine-grained spatial and temporal requirements for robust immunity. Here, using novel single cell datasets, advanced highly-multiplex immunofluorescence imaging, spatial statistics, genetic targeting and in house-developed tools to track the development of immune responses, I aim to 1) create a comprehensive single cell atlas of LN organization in homeostasis, 2) unravel the rules of lymphoid SC specification and organizer function, 3) determine the impact of LN architecture on protective immunity, and 4) determine how such organization is altered in asthma, a highly prevalent chronic inflammatory airway, since alterations in SC-immune cell intercellular communication could explain increased immunity to harmless allergens, in the face of reduce immunity to viral infection and vaccination. By combining my qualifications in SC biology and LN organization with the expertise of the host lab in lung immunopathology, I have created an ambitious work plan that will serve as critical foundation to design future therapeutic interventions that benefit human health.

Mots clés : lymph node, spatial organization, stromal cell heterogeneity, stromal cell specification, stromal cell disfunction, dendritic cells, asthma

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 178320.0 €
Projet BILITOLERANCE (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The immune system was shaped through evolution, primarily through the selective pressure imposed by pathogens. This led to the emergence of multiple mechanisms that limit the negative impact of pathogens on host health and fitness. The best recognized defense strategy against infections relies on resistance mechanisms that aim at pathogen containment, expulsion or clearance. While crucial for host survival to infection, resistance mechanisms can carry significant trade-offs, often driven by oxidative stress and damage imposed to host parenchyma cells, and in some cases compromising the functional output of host tissues, i.e. immunopathology. Presumably for this reason, resistance mechanisms are coupled to countervailing oxidative stress responses that preserve parenchyma tissue function. These provide tissue damage control without exerting a direct negative impact on pathogens and as such are said to confer disease tolerance to infection. This defense strategy relies on the expression of a number of evolutionary conserved effector genes controlling the pro-oxidant effects of iron and heme, as illustrated for the heme catabolizing enzyme heme oxygenase 1 or the iron sequestering protein ferritin H chain. BILITOLERANCE aims at identifying and characterizing an unexplored and possibly central component of this tissue damage control mechanism that relies on the conversion of the end-product of heme catabolism biliverdin into bilirubin, by biliverdin reductase A (BVRA). The central hypothesis to be tested by BILITOLERANCE is that bilirubin generated by BVRA provides a potent lipophilic anti-oxidant defense mechanism that limits the deleterious effects of lipid peroxidation. Moreover BILITOLERANCE will test the hypothesis that bilirubin also signals via the aryl hydrocarbon receptor (AhR) to modulate the activation of tissue-resident macrophages and promote tissue damage control and disease tolerance to infection.

Mots clés : disease tolerance, oxidative stress, biliverdin reductase, bilirubin, infection biology

Participants :
- Calouste Gulbenkian Foundation (Portugal) — Coordinator, beneficiary, Recherche, subvention : 160635.6 €
Projet QoLRO (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The importance of health related quality of life (HRQoL) data in research, clinical practice and health policy has significantly increased over the past decade. EQ-5D-5L is one of the most widely used instruments to measure HRQoL worldwide. Nevertheless, the quality of life of the Romanian general population or ethnic minorities has never been assessed before with EQ-5D-5L. Here, I propose to use EQ-5D-5L to provide locally robust HRQoL data for Romania to support reimbursement decisions and public health interventions in wider and vulnerable groups, such as the Roma minority. A representative sample of the Romanian general population and Roma minority will be recruited and face-to-face interviews will be conducted to explore differences in HRQoL according to sociodemographic characteristics, socioeconomic status and ethnicity. Additionally, population norms and social preferences for different health states (tariff) for EQ-5D-5L will be obtained. The successful delivery of this fellowship will be ensured by a fruitful combination of my experience in quality of life and in psychometric properties of questionnaires with the expertise of Newcastle University in health economics and preference elicitation methods. This fellowship will nurture a dual transfer of knowledge between myself and Newcastle University allowing me to gain new skills in preference elicitation methods, economic evaluations and modelling, teaching and project management. Additionally, the 3-month secondment at the EuroQoL foundation will provide me the skills to successfully undertake fieldwork for population-based valuation studies. These combined experiences will enable me to develop an independent career as a researcher that will play a key role in developing health services research and in building HTA capacity in Romania.

Mots clés : quality of life, eq 5d 5l, valuation study, social inequalities, vulnerable groups

Participants :
- Newcastle University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet ANEMONE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : TERMINATED

The importance of mutualism is underscored by its ubiquity- virtually all of life engages in complex multi-level mutualisms that critically impact the formation and distribution of biodiversity around the globe. Although general expectations exist, no unifying evolutionary theory of mutualism has been established. Largely impeding a synthetic framework for mutualism are incomplete understandings of individual case studies. No mutualism is perhaps more representative of this than the iconic clownfish-sea anemone symbioses, a model mutualism regularly used for exploring fundamental biological processes, but one in which our understanding remains wildly incomplete due to a lack of research into the evolution of the host anemones. Here I propose to use full genome sequencing to conduct the first genomic investigation into the clownfish-hosting sea anemones. I will test: 1) if mutualistic benefits of hosting clownfishes has led to multiple adaptive radiations in host sea anemones, and are thus more diverse than currently described. 2) Whether the mutualistic benefits of hosting clownfishes led to significant ecological opportunity for host anemones, and thus, signatures of demographic population expansion that coincide with the onset of the symbiosis. 3) Whether mutualism with clownfishes has driven convergent genome evolution and architecture among host anemones. 4) The Red King Hypothesis, which states that mutualistic lineages should have slower rates of molecular evolution than their free living relatives. The proposed research will provide novel insight into this iconic mutualism that will bear on the interpretation of dozens of prior studies that span scientific disciplines. Fully disentangling the evolutionary implications of mutualism in this symbiosis will provide critical comparative data from the marine environment in order to more fully evaluate the generalities of mutualism across ecosystems.

Mots clés : i will sequence and assemble full genomes from the clownfish hosting sea anemones to test evolutionary expectations of mutualism

Participants :
- University of Lausanne (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €
Projet SaToBa (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The improvement of crop salt tolerance is a pressing agricultural challenge because salt stress poses a major threat to global food supply. The problem is topical in India where salinity-induced yield losses are increasing for several crops. Compelling evidence indicates that repeated stresses provide a memory to increase tolerance, but the mechanisms are not well understood. This project studies the role of jasmonates (JAs) in priming salt stress memory in barley, one of the most important cereals worldwide for food, malt and animal feed. The main objective is to determine how JAs prime plant salt stress tolerance to overcome the limits imposed on growth and yield. The study will enable the effective use of genetics and genomics to improve salt tolerance by 1) determining the correlation between transcriptome and translatome during growth (inhibition) associated with stress adaptation; 2) characterization of the dependency of the responses from epigenetic changes and the uncharacterized barley JAs receptor COI1, and from the ribosome inactivating protein JIP60. The research will characterize, (A) JAs-primed salt stress adaptation; (B) the mechanisms balancing stress adaptation and growth. To achieve the aims, controlled JAs/salt stress will be applied to monitor organ growth. Growth and cell cycle analyses, alongside RNA-Seq, genome-wide analysis of mRNA translation during development and analysis of specific histone markers will be performed. This will demonstrate how poised gene expression and translation work together to set up stress memory. Plant response to salinity and its impact on yield and metabolism will also be analyzed. This multidisciplinary project will enhance the researcher career prospects when returning to India to establish their own lab continuing work in the same area. Overall, the success of this research will be applicable to other economically important crops worldwide with positive impact on the cultivation of crops during climate change.

Mots clés : jasmonates, stress priming, salinity, barley, genome wide, crispr, cas9

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €