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

Acute Myeloid Leukemia (AML) is the most common adult leukemia, with a high frequency of relapse and mortality. After therapy, the persistence of rare leukemia stem cells (LSCs) with disease initiating and therefore stem cell-like properties is a likely cause for relapse. Therefore, novel therapeutic strategies to specifically eradicate LSCs are urgently needed. Natural Killer-cells (NK-cells) are innate immune cells capable of detecting cell surface ligands to trigger a cytotoxic response against diverse tumor cell types. NK-cells are activated either by missing inhibitory or activating ligands, such as known natural killer group 2D receptor ligands (NKG2DL), which become expressed on target cells upon cellular stress or malignant transformation. The groups of Drs. Trumpp, Lengerke and Salih recently described that LSCs evade the recognition from NK-Cells by repressing NKG2DL expression. Importantly, inhibition of Poly [ADP-ribose] polymerase 1 (PARP1) in a subclass of CD34+ AML patient samples reactivated NKG2DL expression and, when combined with allogeneic NK-Cell therapy, eradicated AML in xenotransplantation models. The goal of this proposal is to systematically discover novel NKG2DL regulators in AML to improve immunotherapeutic therapy options for a broad group of AML patients. I have identified monocytic differentiation and DNA hypermethylation as potentially opposing mechanisms of NKG2DL expression. I will combine single-cell transcriptomic and epigenomic interrogation of AML patient samples to discover how NKG2DL are activated during malignant differentiation and how these processes are impeded by DNA hypermethylation. These approaches, together with genome-wide CRISPR-dCas9 gain of function screens, will help identify master regulators of NKG2DL expression. Lastly, validation of these regulators in AML patient samples will expose vulnerabilities of AML for NK-cell based therapies and elaborate on the previously identified link with AML stemness.

Mots clés : leukemia stem cells, acute myeloid leukemia, nkg2dl regulation, nk cell therapy, immune evasion, aml differentiation, dna hypermethylation, aml single cell transcriptomics, methylomics, crispr dcas9

Participants :
- German Cancer Research Center (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 162806.4 €
Projet NovLeuReg (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Acute myeloid leukemia is a hematopoietic malignancy characterized by the abnormal proliferation of immature myeloid cells. The implementation of high-throughput sequencing revealed that somatic mutations in various epigenetic regulators represent a frequent pathogenic phenomenon in leukemogenesis. This raised optimism for the development of new therapies in leukemia due to the reversible nature of epigenetic marks and amenability of chromatin-modifying enzymes to pharmacological inhibition. However, realization of this potential requires further research into epigenetic mechanisms governing the maintenance of leukemic cells. The overall goal of the proposed work is to characterize novel important epigenetic regulators in leukemic cells and to assess their potential as drug targets. Firstly, I plan to identify and study epigenetic regulators essential for leukemic cells deficient in TET2, an enzyme that hydroxylates methylated cytosines in DNA. This will be achieved by performing state-of-the-art shRNA screens in mouse Tet2-null leukemia models and by exploring the functions of the uncovered candidates using a range of cell biology, biochemistry, and functional genomics approaches. The second aim is to investigate the molecular functions of SETD5, a newly-uncovered epigenetic regulator of leukemic cells. This will be achieved by identifying its target genes and interacting partners in leukemic cells and by exploring the effects of its depletion on normal and cancer cells. The accomplishment of both research aims will provide new insights into epigenetic regulation of leukemic cells and highlight novel drug targets for future therapy development. The project will be supervised by Prof Kristian Helin, a world-leading expert in the field of epigenetics and cancer. Through this work, I aim to broaden my scientific expertise by acquiring numerous technical and transferable skills and to establish myself as an independent researcher in the field of cancer epigenetics.

Mots clés : leukemia, hematopoiesis

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €
Projet StemTarget (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Acute myeloid leukemia is characterized by the accumulation of transformed immature myeloid cell in bone marrow. The course of the disease is marked by poor prognosis, frequent relapse, and high disease-related mortality. In spite of improvements in its therapy, above 60% of AML patients will eventually succumb to the disease, a fact stressing the need for new therapeutic approaches for remission induction and prevention of relapse. The difficulty in treating AML is thought to arise from a chemoresistant subpopulation of leukemia stem cells (LSCs) that are capable of maintaining and reinitiating the disease. Increasing evidences suggest that classic neurotransmitter receptors such as dopamine receptors (DRs) and serotonin receptors (HTRs) are involved in cancer genesis and maintenance. Indeed, DRs and HTRs are expressed on the surface of LSCs. By killing differentially LSCs while sparing healthy hematopoietic stem cells (HSCs), DR/HTR antagonists could constitute a new therapeutic target for AML, especially for eradication of LSCs.

Mots clés : cancer stem cell, serotonin receptors, leukemia, cancer

Participants :
- Leukos biotech sl (Espagne) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 160932.48 €
Projet redTADF (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Adachis pioneering report in 2012 describing TADF emitters based on CDCBs resulted in a paradigm shift in emitter design within the OLED community. Within just five years, highly efficient blue and green purely organic TADF OLEDs have been developed, achieving maximum EQEs exceeding 30%. This means that performance wise, organic TADF emitters have already surpassed the performance of state-of-the-art phosphorescent molecules. However, to date only a handful of red organic TADF emitters exist, with the best EQE reported to date being just 13%, demonstrating a need for continued improvement. European companies such as CDT, Merck, and Cynora are all investing significantly in organic TADF research. The development of high performance organic redTADF emitters will significantly reduce the cost of OLED production and make the devices more environmentally friendly through replacement of the iridium emitters that are currently employed. We propose to develop new highly efficient redTADF dyes based on the ring-contracted systems of subphthalocyanine and subporphyrin.

Mots clés : organic light emitting diodes  oleds, thermally activated delayed fluorescence  tadf, redtadf oleds, boron subphthalocyanine, subporphyrin

Participants :
- University of St Andrews (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet cRETMS (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Adaptation to rapidly changing environmental demands is oneThe adaptation to rapid environmental changes represents one of the most important features of the nervous system. This process is regulated by the influence of the cerebellar output over the motor cortex (M1). Information exchange between the cerebellum and M1 is achieved through rich anatomical connections, and is essential for efficient motor adaptation. However, a macro-scale understanding of the dynamics of this connectom is still poorly understood. The originality of this project is to combine, for the first time, cerebellar rhythmic transcranial magnetic stimulation (rTMS), online electroencephalography (EEG) recordings, and offline diffusion magnetic resonance imaging (dMRI), for the study of cerebello-to-M1 connections. Specifically, cRETMS is articulated in two work-packages (WPs). WP1 will pave the technical ground by probing the hypothesis that cerebellar β-oscillations are physiologically relevant in terms of cerebello-to-M1 anatomical and effective connectivity. WP2 will use the technical proofs of concept coming from WP1 to test the importance of cerebellar β-frequency in the adaptation of motor movements, with the aim of enhancing human motor performance by means of rTMS. The present action may lead to a breakthrough into our mechanistic understanding of cerebellar-to-M1 functional connectivity, which in turn may inform interventions for the manipulation of brain oscillations subtending normal and impaired motor functions. The training provided by my supervisors will be essential to reach these goals. Through them and the excellency of the host institution, this fellowship will give me the opportunity to learn how to analyse diffusion magnetic resonance imaging (dMRI) data, and how to integrate structural and dynamic information coming from the brain. This will undoubtedly increase my chances to further advance my career, deepening my scientific expertise to become an independent researcher.

Mots clés : rhythmic tms, dmri, cerebellum, motor adaptation, connectivity, oscillations

Participants :
- Institut du cerveau (France) — Coordinator, beneficiary, Recherche, subvention : 184707.84 €
Projet ARAMIS (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Adaptive Radiation of Aquatic MIcrobial Species (ARAMIS). The action aims to understand the causes, mechanisms and consequences of adaptive radiation (i.e. the process in which organisms diversify rapidly to occupy ecological niches) in freshwater microbial communities. This will help solve several of the outstanding questions in the field of microbial ecology, such as how shifts in environmental conditions impact the trajectory of microbial evolution, the relative importance of horizontal versus vertical gene transfer in microbial ecosystems, or the definition of microbial ‘species’. As diversity is linked with stability, elucidating the factors driving diversification in freshwater taxa will also help us predict how such ecosystems may respond to future change. ARAMIS proposes the novel hypothesis that, while every freshwater clade has a unique evolutionary history, the environmental forces driving such evolution are fundamentally the same, both in nature and in relative importance. If validated, this simple paradigm would push the state of the art and allow the development of powerful conceptual models integrating environmental constraints, microbial diversification, and community stability. The hypothesis will be tested by combining metagenomics, metatranscriptomics and enrichment cultures over a set of more than 200 lake samples. This will contribute to a conceptual synthesis between community ecology and evolutionary biology by closing the gap between theoretical work and data-driven studies. ARAMIS has a high academic potential but, since it deals with the stability of freswater microbial populations, can also have social and public policy impact by bringing an ecoevolutionary perspective to the management of aquatic resources.

Mots clés : microbial ecology, metagenomics, metatranscriptomics, enrichment cultures

Participants :
- Swedish University of Agricultural Sciences (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203852.16 €
Projet MEGAN (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Adaptive radiation has been pointed out as the main force responsible for phenotypic and taxonomic diversity. Rapid phenotypic evolution and expansion in the morphospace tend to cease as new niches are occupied, and this early burst pattern has been called mega-evolution. The mega-evolution hypothesis explains the diversification patterns of many but not all clades, and the early evolution of some lineages, such as that of anurans, remains obscure. In MEGAN, I will test the mega-evolution hypothesis for anuran diversification based on larval morphology. This proposal comprises three work packages that reflect the main research objectives:1) To determine how larval characters are distributed in the anuran tree of life; 2) To reconstruct the phylomorphospace of anuran larvae; 3) To determine the rates of diversification of anurans based on larval characters. Taxonomic sampling is designed to cover the entire phylogenetic, phenotypic, and ecological diversity of anuran larvae. Transformation series will be individualized from all larval phenotypic systems and characters will be optimized in a time-calibrated; optimizations will be used to reconstruct the phylomorphospace and to estimate evolutionary rates in all branches. MEGAN is aligned with the Horizon 2020 FAIR data management and Open Science, and thus, both data and results will be publicly available. Moreover, I will disseminate and communicate the results of MEGAN in freely accessible medias and scientific events. With MEGAN, I intend to gain new skills that will substantially augment my qualification and enable me to reach a higher level in my career and to perform excellence-level research.

Mots clés : tadpole, morphological disparity, morphospace, phylopmorphospace, evolutionary rates, phenotypes, characters evolution, synapomorphies, diversification

Participants :
- Leibniz Association (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 174806.4 €
- Universität Hamburg (Allemagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet PHEMDD (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Adenosine triphosphate (ATP) is the universal biological energy currency. Its cellular concentration is tightly regulated and depends on rates of glycolysis, oxidative phosphorylation, and obviously on phosphate availability. How is phosphate concentration regulated as a function of the cell’s demands? Inositol pyrophosphates, described as metabolic messengers, are excellent candidates to orchestrate phosphate homeostasis and energy metabolism. The research programme proposed here aims to elucidate the relationships between phosphate homeostasis, energy metabolism, and inositol pyrophosphates using the amoeba Dictyostelium discoideum as a model system. This organism has high levels of inositol pyrophosphates and inorganic polyphosphate (polyP) and, surprisingly, a comparatively low level of ATP, suggesting that inositol pyrophosphates may serve as a phosphate reservoir for ATP production. I will use a combination of metabolomics analysis, steady-state and dynamic flux analysis of ATP, polyP, Pi and inositol pyrophosphate levels, and a functional analysis of mitochondria to evaluate the impact of polyP and inositol pyrophosphates on the metabolic/energetic state of this organism. I will investigate the function of polyP, which is induced during development, to understand how and why phosphate homeostasis is so dramatically modified during this process. This will be the first comprehensive analysis of the relationships between phosphate homeostasis and energy metabolism in eukaryotes.

Mots clés : phosphate homeostasis, energy metabolism, inositol pyrophosphates, polyphosphate

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet HEMOTECT (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Advances in chemistry, biology and medicine have been historically promoted by physical tools, with notable examples x-ray crystallography, nuclear magnetic resonance spectroscopy and microscopy. A new physical tool has recently emerged as a unique electromagnetic-field sensor and it is based on the exploitation of the remarkable magneto-optic properties of one particular color center in diamond, known as the Nitrogen-Vanancy (NV) center. In recent years, nano-scale sensors using NV centers have enabled the detection of nanoscale ensembles of nuclear and/or electron spins, and high-resolution imaging of living cells, to name few of the most outstanding sensing demonstrations using NV centers. We propose the development and implementation of a high-throughput sensor utilizing NV centers in diamonds, for the sensitive, quantitative and rapid detection of ensembles of paramagnetic spins in liquids and crystals. Sensitive paramagnetic-spin sensors will enable the possibility for nanoscale sensing and imaging of the structure and electron configuration of biomolecules, and most importantly, of real-time observations of chemical and biological processes. The principal motivation for the proposed project is the implementation of the developed sensor for the detection of paramagnetic crystals, and in particular of synthetic hemozoin crystals. Synthetic hemozoin crystals have identical magneto-optic properties with naturally-grown hemozoin crystals, a byproduct of malaria infection. A label-free, high-throughput sensor of hemozoin crystals, with sensitivity limits better than the currently used malaria diagnostic techniques will pave the way for a new diagnostic tool that could be used for the early diagnosis of malaria, and therefore, contribute to the eradication of one of the deadliest diseases in the world.

Mots clés : nitrogen vacancy centers, electron spin resonance spectroscopy, paramagnetic spin sensor, label free sensor, hemozoin crystals

Participants :
- Johannes Gutenberg University Mainz (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €
Projet BIPHA (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Advancing our understanding of biologically driven sequestration of carbon is crucial given the rapidly increasing atmospheric CO2 concentrations. Diatoms are the most common type of phytoplankton and, as the ocean’s biological carbon pump, a key component in this process. Diatom aggregates, in particular, comprise a significant fraction of sinking particulate matter drawing down atmospheric carbon to the depths of the ocean. Diatoms produce transparent exopolymeric particles (TEP), a gel-like sticky sugary substance, which plays a significant role in the subsequent coagulation of diatoms into aggregates as their blooms terminate. These sinking aggregates are composed of diatoms, detritus and faecal pellets and are so-called marine snow aggregates. We will use recent innovations in technology to study the role of TEP content for: • Scavenging of particles • Flow and diffusion within and around diatom aggregates We will draw upon the specialized expertise of the applicant and the beneficiary to study diatom aggregates in detail using methods which have greatly profited from technological advances: • Particle image velocimetry, and • digital holographic microscopy, in combination with • microsensors, to study mass transfer at a sub-mm scale. The methods will enable us for the first time to quantify directly any flow inside the aggregates, also called the interstitial fluid flow, and to visualize the aggregate’s structure and particle composition. Targeting these processes with advanced instrumentation will bring European research on aggregates to the forefront in terms of the technology, but more importantly, our understanding of carbon cycling in the ocean and our position on future climate change impacts.

Mots clés : marine snow, aggregates, diatoms, biological carbon pump, transparent exopolymeric particles, particle image velocimetry, digital holography, flow, mass transfer, scavenging, coagulation, pores

Participants :
- University of Gothenburg (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173857.2 €
Projet BactoBubble (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Aerial transport of microbes has fundamental consequences for microbial dispersal, disease spreading, and atmospheric phenomena. In the ocean, aerosolisation largely originates from collection of bacteria by rising bubbles, which burst at the surface and eject cells in microdroplets. This process underlies the enrichment of bacteria in aerosols. While we know that collection rates vary among bacterial species, we know little about the bacterial properties promoting collection, and even less about which factors drive enhanced collection of certain species. Combining state-of-the-art microfluidics and microscopy, I will provide the first microscopic observation of bubble-bacteria interaction, to investigate two hypotheses: H1: Cell motility increases microbial collection by rising bubbles. Motility sets bacteria starkly apart from inert particles, likely promoting collection by increasing encounter rates and changing surface properties. H2: Starvation increases microbial collection by rising bubbles. Starving bacteria modify their surface and size, which may enhance collection by bubbles, thereby promoting dispersal from nutrient poor areas. To investigate H1 and H2, I will develop a novel microfluidic flow channel containing a pinned bubble, and use advanced optical microscopy to quantify collection rates for a range of bacteria. Experiments using mutants to alter motility (H1) and varying starvation levels (H2) will be complemented by characterization of bacterial surface properties. I will also develop the first mathematical model predictive for microbial aerosolisation. This project builds on my experience in modeling and interfaces, enhanced by training in microfluidics and marine microbial ecology within an internationally recognised multidisciplinary group, in order to open an innovative domain linking microscale interactions with global-scale scientific, environmental and societal impacts, and provide a springboard towards an independent research career.

Mots clés : bacteria, aerosolisation, rising bubble, microfluidics, microbial dispersal, air water interface, motility

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175419.6 €