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

Aging is a major risk factor for many human pathologies. At a time when we are living longer than ever before, untangling the mechanisms of this biological deterioration is absolutely critical if we aim at providing a better quality of life for aging individuals. The loss of nuclear integrity, and the consequent defects in nuclear mechanics, is already among widely considered hallmarks of aging. In mammalian cells, the structural properties of the nucleus are maintained by the nuclear lamina (NL), especially lamin A (LA), and its interaction with the nuclear envelope (NE). In this innovative project, our working hypothesis is built upon the observation that progerin – truncated form of LA prevalent in premature aging – is abnormally associated with the inner nuclear membrane (INM) and the LA, due to its permanent farnesylation. Moreover, progerin levels were also shown to increase in healthy aged individuals, suggesting that LA and progerin differences in membrane association might be intimately involved in healthy human aging. Hence, the main goal of this project is to understand how the interplay between LA (at different proteolytic stages) and INM lipids affects NL architecture and nuclear structural integrity during physiological aging. To address this question, we will tackle lamin-lipid interactions (and lamin polymerization) in membrane models mimicking the NE during healthy and premature aging, and in intact nuclei, using a set of quantitative techniques, including fluorescence-based methods, atomic force microscopy and lipidomics. Overall, this is the first time a comprehensive lipid-driven molecular biophysics approach will be applied to the NE during healthy human aging. By achieving the proposed objectives, we will provide new knowledge on the role of INM lipids in proper nuclear function and aging.

Mots clés : molecular biophysics, inner nuclear membrane, nuclear structural integrity, lamin a polymerization, lamin lipid interaction, human aging, fluorescence spectroscopy and microscopy, lipidomics

Participants :
- University of Lisbon (Portugal) — Coordinator, beneficiary, Recherche, subvention : 147815.04 €
Projet OPTIMISE (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Aging populations and the increasing use of immune modulatory medical treatments have given rise to a growing incidence of opportunistic infections. Legionella species are Gram-negative environmental bacteria, which after accidental inhalation can cause respiratory infections with symptoms reaching from a mild flu to a severe pneumonia, called Legionnaires’ disease. Disease progression, i.e. clearance or exacerbation of infection, is determined by the immune status of the host and acute pneumonia usually associated with immune suppression and/or underlying pulmonary conditions, but the molecular mechanisms enhancing susceptibility are poorly understood. The infection biology of Legionella has been studied mostly in cellular infection models and mice, which do not develop human-like disease. As patients typically present only at late stages of infection, it is unclear to which extent findings from these models reflect the early processes which occur in the human lung during infection and how these drive the clinical outcomes. Similarly, these models fail to explain, why L. pneumophila serogroup 1 strains are the predominant cause of more than 90% of Legionnaires’ disease cases. In this project I, the applicant Dr. Flavia Viana, will tackle these knowledge gaps by establishing and using human precision cut lung tissue slices (hPCLS) and excorporeal perfused whole human lungs (Ex vivo lung perfusion (EVLP)) as infection models for Legionella. I will determine if and how virulence of different Legionella isolates in these models correlates with their relevance in the clinical practice, analyse the transcriptional responses of all cell types in the infected human tissue using single cell transcriptomics and employ histology, state-of-the-art confocal and light sheet live microscopy, to visualise infection dynamics and host responses, providing unprecedented insight into the molecular events leading to the development of Legionnaires’ disease.

Mots clés : legionella, bacterial pathogenesis, virulence factors, host pathogen interaction, respiratory medicine, lung tissue models, precision cut lung slices, single cell transcriptomics

Participants :
- Queen's University Belfast (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet FOMN (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Agricultural ecosystems currently comprise approximately forty percent of the terrestrial surface of the earth. In addition, the impacts of agricultural practices extend far beyond the boundaries of crop fields. The drift and runoff of chemicals applied to croplands directly impact the flora and fauna of surrounding biomes. For example, the amount of fertiliser required to maintain the high productivity of modern cropping systems has impacts on the soil microbiota, the species density and primary productivity of plants, and interacts with disturbance to alter the species composition of plant communities. Much less is known about the effects of soil fertilisation on interactions between plants and insects, though preliminary research indicates that soil enhancement can in fact alter pollinator visitation. Our primary objective is to determine the indirect effects of fertilisation on the structure of mutualistic plant-pollinator communities. This work is motivated not only by an interest in the ecosystem services provided to agricultural systems by pollinators, but also by a conservation interest in the impact of fertiliser runoff into surrounding natural habitat. This research will allow us to discuss the potential cascading impacts of widespread fertilisation practices on mutualistic interactions in agricultural and natural ecosystems. In addition, it will improve our understanding of how complex community interactions are formed and influenced by resource availability, with consequences for the fitness of both interacting partners.

Mots clés : mutualistic interactions, ecological networks, fertilisation, agroecosystems, ecosystem services, pollination biology

Participants :
- Trinity College Dublin (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175866.0 €
Projet CarboPlex (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Aim of this project is to investigate and exploit the potentials of a new material termed biochar-mineral complex (BMC). The simple yet ground-breaking idea is to use common waste streams to produce BMCs with distinct properties. Primary target is the use of BMCs as soil amender, especially in soils, where the delicate but crucial structure of organo-mineral complexes is threatened by unsustainable soil use or climate change. Where pure biochar is known to face its limits, BMC because of its mineral part is assumed to enable much higher functionality (i.e. water and nutrient storage). To provide evidence-based information on production, properties and soil effects of BMC, a systematic study will be conducted. The highly interdisciplinary work is split into five strongly interconnected work packages, which cover the whole BMC lifespan from production to soil use and technology assessment. Most of the work will be conducted at the University of Edinburgh (UoE). A secondment is planned at Enrich Environmental Ltd., an innovative Irish waste treatment SME, where the potentials and requirements for successful large-scale implementation will be investigated. Introducing this original work to the scientific communities (i.e. waste, agriculture, soil, material science) is expected to make enormous impact. Strong attention is also paid to dissemination of the results to the industry, other stakeholders and the general public. The ER, in addition to the expected excellent research, profits greatly from new experiences with pyrolysis (UKBRC) and business management (Enrich) supporting his strive for an academic career as professor. The UoE benefits from the ER’s experiences in hydrothermal carbonization and gaining competence in BMCs. Enrich, in return, has strong interest to expand its range of products and to integrate innovative processes such as BMC production. Naturally, the ER, UoE and Enrich are strongly committed to the planed action and a most successful outcome.

Mots clés : waste treatment, biochar, pyrolysis, hydrothermal carbonization, soil amendment

Participants :
- University of Edinburgh (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet CEMoS-OFC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Air pollution is an increasingly important concern in larger cities and industrial areas. To date, much attention has been devoted to monitoring of particulate matter (PM), yet sensing of toxic or cancerogenic gas species formed i.e. in combustion of low-quality fuels is still challenging. The new National Emissions Ceilings (NEC) Directive (2016/2284/EU) has set commitments for member states on several important air pollutants, of which two groups: non-methane volatile organic compounds (NMVOCs), and persistent organic pollutants (POPs) are difficult to monitor using existing electrochemical or laser-based technologies to ensure sufficient sensitivity and selectivity. To address this need, the objective of this proposal is to develop a novel class of broadband and high-resolution laser spectrometers for open-path atmospheric monitoring. The instrument will exploit a pair od optical frequency comb (OFC) sources, which operate in the spectroscopically-relevant mid-infrared region where NMVOCs and POPs have their strongest and most unique absorption features. Unlike all prior attempts, this project aims to advance the field by enabling completely unstabilized operation of the sources using real-time computational signal enhancement referred to as Computationally Enhanced Molecular Sensing with Optical Frequency Combs (CEMOS-OFC). By generating two mutually coherent OFCs in a shared cavity, the need for complex phase synchronization electronics in dual-comb spectroscopy is eliminated, which paves the way for practical out-of-laboratory measurements of multi-species gas mixtures over open-path channels reaching hundreds of meters corresponding to part-per-million to parts-per-billion sensitivities. In addition to environmental gas sensing, spectroscopic analysis of simple algae and pharmaceuticals in the mid- to far-infrared region is also proposed.

Mots clés : optical spectroscopy, mode locked lasers, environmental sensing, detection of complex molecules

Participants :
- Wrocław University of Science and Technology (Pologne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 149625.6 €
Projet MAPAA (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Al-Cu alloys have a wide range of engineering applications due to their low density and high strength provide by a fine dispersion of nm-sized precipitates. The optimization of the mechanical properties of these alloys has been traditionally carried out through costly experimental “trial-and-error” approaches. In this project, a novel methodology is presented to determine the precipitate structure resulting from high temperature ageing and the resulting strength of the alloys from first principles calculations. The strategy is based in two main pillars. The first one is the determination of the Al-rich part of the Al-Cu phase diagram by means the construction of effective cluster expansion Hamiltonians that can extrapolate first-principles calculations in combination with statistical mechanics approaches based on Monte Carlo simulations to include the entropic contributions, enabling parameter-free predictions of the phase diagram. The second one is the combination of this information with phase field modeling to predict the homogeneous and heterogeneous nucleation and growth of precipitates during high temperature ageing and with molecular dynamics and dislocation dynamics simulations to predict the strengthening provided by the precipitates. The approach developed in this proposal will improve the predictive power of Integrated Computational Materials Engineering in Al-Cu alloys. The applicant will transfer her expertise and international connection in the field of multiscale modelling to the host institute. She will work with researchers of the host institution to prompt new areas of research that can attract new funding and receive regular training on transferable skills. All these activities will enlarge her portfolio of skills and will ensure further development of her career.

Mots clés : al cu alloys, phase diagram, first principles, statistical mechanics, effective hamiltonians, monte carlo, precipitate, phase field, molecular dynamics, dislocation dynamics

Participants :
- Madrid Institute for Advanced Studies (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet ASTRO-EDITING (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Alexander disease (AxD) is an autosomal dominant neurodegenerative disorder caused by missense mutations in the gene encoding the glial fibrillary acidic protein (GFAP), the major intermediate filament protein in astrocytes. Accumulation of GFAP aggregates in Rosenthal fibres leads to impairment of proteasomal activity and hyperactivation of the stress response, thus compromising astrocyte functions and altering the homeostasis of the central nervous system (CNS). Currently, this orphan disease lacks a cure. The proposed project aims at providing in vivo proof-of-concept of safety, efficiency and efficacy of a novel and definitive AAV gene therapy approach based on gene editing / base editing strategies targeting GFAP mutational hotspots to recover pathological phenotypes in astrocytes. The candidate expects to outline novel editing platforms for widespread in vivo targeting of CNS astrocytes that could be applied for the treatment of AxD, as proposed in ASTRO-EDITING, and prospectively for disease modelling studies and therapeutic treatments of other neurological and psychiatric disorders by targeting pathological pathways involved in primary astrocyte degeneration or dysfunctional/maladaptive astrogliosis. The proposal addresses the European issue of Horizon 2020, in the social challenge “Health, Demographic Change and Wellbeing” endeavours for the call “Better health and care, economic growth and sustainable health disease”, subject SC1-BMC-04-2018 “Rare Disease European Joint Programme Cofund”. The expertise of the host laboratory, the international environment of OSR and the personalized career development plan will significantly reinforce candidate's competences and knowledge in the gene therapy field, expand his portfolio of therapeutic areas, create a new research niche, and strengthen his organizational, management and interpersonal skills, thus favouring the progressive acquisition of independence as experienced researcher in the scientific community.

Mots clés : alexander disease, astrocytes, autosomal dominant neurological disorders, crispr, cas9 system, gene editing, base editing, in vivo gene therapy, adeno associated viral vectors

Participants :
- Istituti di Ricovero e Cura a Carattere Scientifico (Italie) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 183473.28 €
Projet TETRASYN (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Alkene-containing molecules and their derivatives play a major role in medicine, food and energy production, as well as materials research and polymer science. In most applications, particularly in medicine, alkenes are needed in isomerically pure form. While strategies for stereoselective preparation of olefins have been the subject of substantial interest, methods relating to synthesis of tetrasubstituted alkenes are uncommon, especially those that are catalytic. What is more, the small number of available protocols are often not highly selective or broadly applicable. The goal of the proposed studies is to introduce a practical, scalable, modular and highly stereoselective synthesis of a large assortment tetrasubstituted alkenes from readily available Cu-based catalysts, nitriles, allenes, and a commercially available diboron compound. The tetrasubstituted alkene products will contain readily modifiable functional groups, such as a ketone, an ester, and a boronate moiety, thus offering direct access to a larger collection of otherwise difficult-to-prepare and much sought-after derivatives. The applicability of the approach will be highlighted by a concise and practical gram-scale stereoselective synthesis of two important bioactive compounds. The first will be neocurcumenol, a natural product with anti-inflammatory properties, and the second will be acolbifene, currently in third phase clinical trials for treatment of breast cancer. Equally important, the versatility of the catalytic strategy will allow for facile preparation of host of related analogues – entities that might display superior pharmacological properties and cannot be synthesized easily by the available methods.

Mots clés : bioactive compounds, catalysis, stereoselective synthesis, tetrasubstituted alkenes

Participants :
- Université de Strasbourg (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196707.84 €
Projet ASIMOF (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Statut du projet : CLOSED

All animals need to solve some key tasks in order to survive: they need to find food, mates, and avoid threats. To do this they have evolved sensory systems of various modalities, to obtain relevant information from their environment. However, sensation does not happen in isolation: in order to respond to salient environmental cues, sensory information needs to be coupled to movement, and thus motor systems. Furthermore, sensation itself is an active process: animals sense environment by moving in it. This movement in space (whether eyes scanning the environment, or the animal itself moving through it) sets the reference frame for sensory information. We have developed a virtual reality arena that allows online tracking of the fly locomotion, and control of their visual environment. When exploring their environment Drosophila locomotion consists of straight runs and fast saccadic turns. However, when sensing a directional aversive cue (the heated wall of the arena) the flies perform a fast, evasive saccadic turn directly away from it. In order to do this optimally, they need to integrate their self-motion with the aversive stimulus, by using the former as a reference frame for the latter, and compute the angle of the evasive maneuvre. We will use this active sensation behaviour (with components of self-motion, spatially localized sensory signal, and a directional motor response) as a model for how the fly brain responds to sensory stimuli in space. We will first assess the behavioural capacities of the flies in this context, and whether their behaviour changes as a function of experience. We will identify underlying visuomotor pathways by functional imaging of targeted neurons while the flies are performing the behaviour in a virtual reality environment, and by Electron Microcopy based reconstruction of neuronal connectivity. Finally, we will determine the computations that the underlying circuits are performing by combination of functional imaging and modelling.

Mots clés : sensorimotor integration, navigation, connectomics, imaging, virtual reality

Participants :
- Champalimaud Foundation (Portugal) — Coordinator, beneficiary, Recherche, subvention : 147815.04 €
Projet ESEMT (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Alternative splicing (AS) is a highly regulated process that is essential for creating the protein diversity required for correct cell-type specification. Misregulation of AS programs can lead to cellular dysfunction, developmental problems and disease, such as cancer. Understanding how alternative splicing is regulated during development and disease is therefore capital. Recent advances in the field have shown that, not only does AS regulation rely on the recruitment of various splicing factors to the pre-mRNA, but other phenomena such as RNA Polymerase II elongation rate, histone post-translational modifications or long non-coding RNAs have been shown to regulate this process. I hypothesize that transcriptional enhancers also play a critical role in the establishment and maintenance of cell-type-specific AS programs. I propose to study the effect of enhancer activation on AS regulation during the epithelial-to-mesenchymal transition (EMT), an important physiological process involved in tumour metastasis and cancer recurrence. Using genome-wide studies, I will map and physically link activated enhancers to intragenic regions of alternatively spliced genes over the course of the EMT in human mammary epithelial cells. I will then employ a candidate-based approach to tease apart the multiple processes through which enhancer activation can regulate splicing patterns, and to discover new enhancer-linked regulators implicated in the AS process. Long-term, this project aims to establish a direct functional link between enhancer activation and alternative splicing during development, with the ultimate ambition of being able to modify AS patterns through the regulation of enhancers. This study will yield results expected to have important implications for the understanding of how cancer-specific splicing programs are established and maintained and have the potential to discover innovative targets to revert EMT and in this way reduce tumour metastasis and cancer progression.

Mots clés : enhancer, alternative splicing, cancer, 3d interactions, epigenetics

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €