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

In eukaryotes, gene expression is highly regulated involving multistep pathways in which mRNA plays a crucial role. Cells have evolved surveillance mechanisms able to detect and degrade defective transcripts. Nonsense-mediated mRNA decay (NMD) is a mRNA surveillance mechanism which detects faulty mRNAs with premature termination codons (PTCs) and targets these transcripts to decay. By modulating the expression of physiological mRNAs, NMD acts as a post-transcriptional regulator controlling important cellular processes in development, stress response, immunity and neuronal differentiation. NMD is of medical importance because mutations or copy number variations of the NMD factors are implicated in human neurological disorders, intellectual disability, schizophrenia, autism, immune diseases and cancer. The mammalian NMD machinery comprises the proteins UPF1, UPF2, and UPF3B, eukaryotic release factors (eRF1 and eRF3a), SMG1 kinase and SMG5-9. Recently UPF3B was found to have a role in translation termination at a premature stop codon, interacting directly with the ribosome, release factors and UPF1, requiring modification of prevalent NMD models. To understand the molecular mechanisms of UPF3B and its role in NMD, this proposal aims to determine the molecular architecture of UPF3B in complex with UPF1, ribosome and mRNA. Furthermore, I will explore the role of the helicase and ubiquitin ligase activities of UPF1 in NMD and protein decay. I will use biochemistry, biophysics, X-ray crystallography and cryo-electron microscopy to identify the UPF3B domains involved in the recognition of NMD substrates and to investigate how UPF3B binding to the UPF1-RNA complex helps trigger mRNA decay. Such information will shed light on how translation termination and assembly of the NMD machinery are coordinated and therefore will be of key importance for the future development of therapeutic approaches for the future development of therapeutic approaches for NMD- related diseases.

Mots clés : non sense mediated decay, mrna quality control, mrna surveillance, translation termination, ribosome, upfs proteins, biophysics, protein protein interactions, proteomics

Participants :
- University of Bristol (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet EPIDNA (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

In eukaryotic cells, gene expression is regulated by a complex interplay between a number of factors, from large-scale chromatin accessibility to inducible enhancers or repressors to local DNA modifications, changes in nucleosome architecture and specific histone markers. These finely tuned factors coordinate embrional development, response to stimuli and changes in cell fate. At the same time, this regulatory network has to robustly accommodate random events, most notably the presence of DNA damage and the action of DNA repair factors. While recent reports suggest this interplay is not always smooth, our mechanistic understanding of the underlying processes is severely limited, highlighting the need for quantitative approaches that will yield predictive models. In this proposal, I plan to investigate three aspects of this interplay that recently came into the spotlight. Firstly, an integrative computational and experimental approach will be used to quantify the positioning effect resulting from a range of common DNA modifications: regulatory base variants that can be used to enforce specific nucleosome patterns, and damage byproducts that would thereby interfere with DNA repair through altered exposure to the environment. Secondly, a number of transcription factors will be systematically assessed to detect ones sensitive to the presence of the most common oxidative lesion, 8-oxoguanine, to identify possible direct cross-talk between oxidative stress and transcriptional regulation at oxidative hot spots. Finally, a multiscale quantum/classical study will explore the thermodynamics, mechanism of formation and possible nucleosomal locations of covalent histone-DNA cross-links that were recently postulated to both mediate the regulatory role of 5-formylcytosine and accelerate strand scission at abasic sites.

Mots clés : dna damage

Participants :
- Institute for Research in Biomedicine (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet Human Rpc5 (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

In higher eukaryotes, the RNA polymerase III (Pol III) participates in the transcription of small RNAs such as the tRNAs. RNA polymerase recruitment to their specific promoter relies on the activity of several transcription factors. Brf2 is a transcription factor that exclusively recruits RNA Pol III at the selenocysteine tRNA (tRNASec). Unpublished work from our group has unravelled an unanticipated central role of Brf2 in the oxidative stress response pathway, by acting as a cellular blockade during prolonged oxidative stress. We are interested in understanding the molecular determinants that govern RNA Pol III recruitment at tRNASec promoter and its interaction with Brf2-bound promoters. In general, RNA Pol III subunit’s size is conserved amongst the eukaryotic kingdom. However, an exception is the human Rpc5 subunit, whose C terminus has 450 residues that are not present in its yeast counterpart C37. Similarly to Brf2, the Rpc5 C-terminal extension is only present in higher metazoans, which suggests a phylogenetic link between these two proteins. The recruiting mechanism of RNA Pol III to Brf2-dependent promoters has not been described to date. Preliminary results in our lab provide evidences that indeed Rpc5 C terminus is responsible for the accurate recruitment of RNA Pol III at TBP/Brf2/DNA complex. Interestingly, structural homology predictions indicated that the human Rpc5 C-terminal extension is a eukaryotic homologue of the prokaryotic protein SelB, a factor that interacts with the tRNASec and with a specific region of mRNAs, the SECIS-element, during translation of SeCys containing proteins. This similarity suggests a regulatory role for Rpc5 C terminus in the interaction with the SECIS-element and/or the tRNASec. Our main objectives are to determine the structure of the Rpc5 C terminus in isolation and in complex with Brf2/TBP/DNA by X-ray crystallography and to characterise the role of Rpc5 C terminus in the context of tRNASec transcription.

Mots clés : rna polymerase iii, gene transcription, brf2, selenocysteine trna, structural biology

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet OBSTETRICVIOLENCE (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

In many European countries, childbirth still includes a variety of routine medical interventions, such as labour-inducing drugs, the lithotomic position, epidurals, manoeuvres, episiotomy and an excess of surgical deliveries. These also happen for women with low-risk pregnancies, despite WHO recommendations and the findings of evidence-based medicine on the topic. Sometimes women can be coerced into accepting medical interventions, or these interventions are performed without their consent. In Latin America, over the past decade, the term “obstetric violence” has become part of the legal framework. The concept refers to acts in the context of labour and birth categorised as physically or psychologically violent due to unjustified use of medical interventions. Specific laws against obstetric violence – a type of gender-based violence – exist in Argentina (2009), Venezuela (2007) and Mexico (2014). In Europe, the issue is discussed by human rights organisations and social movements in order to fight for a more respectful birth, but no country has passed legislation on the matter yet. The project aims to reconstruct and analyse the historical, social and political processes that led to the legal recognition of obstetric violence in Latin America, focusing on the experience in Argentina. The impact that this recognition has had on birth care services and the training of health personnel will be analysed. A qualitative methodology based on case studies and social actors’ perspectives will be adopted. Medical anthropology – with contributions from disciplines such as community health, human rights and gender studies – will provide the theoretical framework for the project. Tools and best practices will be identified and transferred at the European level in order to contribute to the public debate on a respectful birth and to support a process of political recognition of obstetric violence in the European context. An Observatory on Obstetric Violence will be implemented.

Mots clés : obstetric violence, birth care, medicalization of birth, childbirth, birth policies

Participants :
- University of Udine (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 153381.6 €
- Universidad Nacional de Lanús (Argentine) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet EVOLMARIN (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

In marine ectotherms, the breadth of physiological tolerance largely determines species’ geographical distribution and extinction risk. Understanding the mechanisms underlying environmental tolerance windows and their relation to life history and demography is thus required for predicting taxa sensitivity to global changes more accurately. Specifically, it is imperative to acquire a firm understanding of both plastic and adaptive responses as rescue mechanisms to prevent species extinction, comparing the effects and costs of these mechanisms among closely related species with different biogeography. I propose to compare the capacity for trans-generational plasticity and rapid adaptation to ocean warming and acidification, in geographically widespread and restricted species as a test for biodiversity evolution under global change. My aims are to (1) define if rapid adaptation to multiple stressors can occur, searching for correlations between plastic/evolutionary responses and the width of species geographic range, (2) reveal potential costs associated with plastic/adaptive responses, and (3) draw projections on species demography, persistence, and biogeography under different global change scenarios. To do this, I have identified an ideal study system for which this information can be gathered in phylogenetically closely-related species with similar ecology, but different biogeography, i.e. eight polychaete species of the genus Ophryotrocha (Dorvilleidae). This ambitious project, which draws from the fields of comparative physiology, ecology, and evolution, relies on an innovative, integrative approach that combines experimental evolution, quantitative genetics, macrophysiology and evolutionary theory. More important, it represents an unprecedented opportunity to produce reliable generalisations on the fate of future biodiversity patterns in a changing ocean, which is essential in designing pro-active strategies to reduce global change impacts on biodiversity.

Mots clés : biodiversity, comparative methods, adaptation, transgenerational plasticity, fitness, trade offs, biogeography, heritability, physiology, life history, demography, ocean warming and acidification

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 250160.4 €
- Université du Québec (Canada) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet Photo2Bio (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

In my research proposal Photo2Bio, I introduce a conceptually new chemical paradigm for the organocatalytic asymmetric CO2 fixation via synergistic catalysis. This strategy demonstrates its straight to the synthesis of amino acids and diverse complex molecular architectures using renewable sources: light and CO2. The key features of this strategy is to develop a dual catalytic system which can simultaneous activate both coupling partner: the organic substrate and CO2, thus combining two powerful fields of molecular activation: visible light photoredoxcatalysis and organocatalysis. After the development of the discovery phase - development of the dual catalytic system and application to the synthesis of biomolecules - a more applicative execution phase will take place, where organocatalytic magnetic nanoparticles (MN) will be implemented and functionalize to overcome the recovery and catalyst loading issues. This will open the way to environmentally benign industrial applications. The successful development of proposal is ensured by the merging of diverse skills from hosting group at the University of Padova, led by Prof. Marcella Bonchio i) CO2 valorisation, ii) photocatalyst; the ITM-CNR expert in MN Dr. Alberto Figoli: i) magnetic nanoparticle design and assembly and me: i) photoredox catalysis, ii) asymmetric synthesis and reaction development. Funding of the Photo2Bio will generate great benefit not only for academia and industry through the synthesis of chiral biomolecules but also for the society. At short term new sustainable way to bioactive molecules will be accessed; at a long term this will serve to prove the concept that chemistry useful and can solve global warming by the development of sustainable synthetic methods, thus changing the common people perception of chemistry as toxic and/or dangerous. This will be accomplished by a series of large audience initiative and discussions with scientists and common people.

Mots clés : photocatalysis, organocatalysis, co2 fixation, amino acids, asymmetric synthesis

Participants :
- University of Padua (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183473.28 €
Projet SynapseER (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

In neurons, endoplasmic reticulum (ER) organelle shows physical continuity between dendrites, cell body and axonal presynaptic terminals, and has been termed “a neuron within a neuron”. The importance of ER in axons is suggested by the fact that mutations of ER-shaping proteins result in hereditary spastic paraplegia (HSP), a motor axon degeneration disease. ER is present in presynapses, and mutations of ER-shaping proteins disrupt synaptic morphology or function. However, the physiological roles of ER distribution in this context are largely unknown. The time to study the roles of ER distribution in presynaptic terminals is opportune: new HSP-associated genes encoding ER proteins are being identified continuously in human patients; studies in non-neuronal cells identified several HSP-gene-encoded proteins as ER-shaping proteins - to date these have not been examined in synapses; there is increasing data about the nature and roles of contact sites between ER and other cellular structures, whose functions are required at synapses. Drosophila is a successfully used model for neuronal cell biology and degeneration, which reduces use of regulated vertebrates; my sponsor has developed tools to detect impaired neuronal ER organisation in Drosophila; and emerging microscopy techniques allow ultrastructural analysis and 3D reconstruction of the ER network. My work will specifically examine the distribution and role of ER at presynaptic level for the first time, and mechanisms of dysfunction that are relevant for human neurodegenerative diseases. I will study neuromuscular junctions in wild-type and in Drosophila mutants for HSP ER-shaping proteins, to understand the roles of these proteins and the consequences of any altered distribution for local trafficking and organelle function. To address this aim, I will use electron and super-resolution microscopy, and using light microscopy markers I will undertake structural and functional characterization of ER distribution.

Mots clés : endoplasmic reticulum, hereditary spastic paraplegia, motor neuron, synapse, neuromuscular junction, drosophila

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet INTRANCES (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

In order to ensure full compliance with EU policy objectives for climate, air quality and sustainable development integrated transport strategies are needed for Europe’s towns and cities. However, incorporating such schemes into broader urban planning strategies is challenging, and achieving stakeholder buy-in often means the difference between success and failure. The INTRANCES project engages key stakeholders (land use and transport planning experts and transport users) in integrated participatory modelling of land use and transport scenarios to help address EU policy goals. The aim of the project is to test the feasibility of different transport strategies, identify win-win solutions that simultaneously address multiple goals, and signal potential problems in implementation leading to recommendations for sustainable transport policy in Madrid and other cities across the EU. Building on the fellow’s previous experience in participatory land use modelling, and the host’s significant expertise in policy relevant transport research, INTRANCES develops an urban simulation model to output indicators for land use, transport and energy and emissions based on scenarios developed by key stakeholders. In addition to this knowledge exchange between host and fellow, the fellowship draws on the additional knowledge of key experts in air pollution modelling, urban planning, and integrated scenario modelling, including a 3-month secondment at a commercial consultancy in the Netherlands. This multi-way process of knowledge exchange is of high strategic value to the host and secondment partner and is expected to significantly enhance the fellow’s career prospects, both in academia and beyond. Its research objectives will lead to insights and recommendations for current and future efforts to implement sustainable transport across the EU.

Mots clés : participatory scenario planning, integrated modelling, sustainable transport, energy, emissions, climate, land use

Participants :
- Universidad Complutense de Madrid (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet NucSat (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

In our societies in which information is ubiquitous, satellites are still a matter of national pride and prestige, but they are also scientific laboratories, commercial projects, services’ providers, and part of global information infrastructures. Satellites are part and parcel of knowledge society. In particular, satellite images and calibrated measurements contribute to generate technical information about nuclear accidents, as well as to convey the public perception of them, forge debates on nuclear energy, its management and its risks, and shape environmental, regulatory and political action. Satellite data are both resources that enable regulators and policy-makers to act during and after nuclear crises as well as instruments to communicate with the large public. But how policy guidance is carried out to manage nuclear situations and how public perception of nuclear risks is constructed from, through and with satellite data? By focusing on the information generated and consumed in the aftermath of two nuclear accidents (Chernobyl 1986 and Fukushima 2011), this project aims to explore in detail the processes that transform satellite raw data into knowledge, allowing us to understand how satellite information is produced, analysed, rendered evident, disseminated and consumed. Such historically informed comparative study will provide understanding of the historical evolution of the production, circulation and reception of satellite data and their actual impact in the contexts of both defining political action and framing public opinion related to nuclear issues. This innovative study will not only enhance our academic understanding of space, nuclear and information history (and their connections), but also alert us to how knowledge from space is generated as it is transformed into information that is used to advance multiple intellectual, institutional and policy-related objectives in different social and cultural contexts.

Mots clés : satellite data, nuclear accidents, information society, science, technology and society, public understanding of science and technology, technology and risk communication

Participants :
- Pompeu Fabra University (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet TRIDOS (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

In radiation therapy (RT), which is used in more than 50% of cancer treatments, the dose delivered to the tumour/normal tissue determines tumour control and toxicity. Targeted radionuclide therapy (TRNT) is an effective growing type of RT in which radiative compounds with high tumour affinity are administered to patients. While in external RT there are well-defined methodologies to accurately determine the dose, this is not the case in TRNT. Traditionally, TRNT dosimetry is obtained from simple biokinetic models, developed many years ago, and non-individualized dosimetric factors calculated in phantoms. This dosimetry is inaccurate and not patient individualized. The recent European council directive 2013/59/Euratom, transposed on Feb 2018, has clearly highlighted the need to accurately report all doses from radiopharmaceutical procedures, hardening the criteria of previous regulations. The objective of this project is to develop methodologies for the accurate, individualized dosimetry and radiobiological assessment of TRNT, shifting from the current paradigm of empirical treatment to the era of personalized treatment. This will be achieved by the following actions: a) adaptation of Monte Carlo codes for patient’s internal dose calculation, considering novel biokinetic models of the drug biodistribution; b) development and implementation of radiobiological algorithms to evaluate tumour control/toxicity; and c) implementation of a platform useful for the clinical practice, incorporating these models and allowing easy handling and user interactivity. To successfully address this, the researcher experience will be combined with the host organisation (FIDIS) capabilities, a leading biomedical research institute where the supervisor is already involved in TRNT research. FIDIS will also provide clinical data for the models development/validation, an interdisciplinary environment and a training program greatly contributing to re-enforce the researcher professional maturity

Mots clés : cancer, targeted radionuclide therapy, dosimetry, monte carlo, radiobiology, metrology

Participants :
- Instituto de Investigación Sanitaria de Santiago (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €