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

Modulation of gene expression is key for maintaining cellular homeostasis in the changing environment. It is achieved through controlling the processes of transcription and RNA degradation that ultimately affect abundance and composition of the mRNA pool. Emerging evidence suggests that the pathways of RNA surveillance and degradation are of paramount importance for fast adaptation of gene expression to stress. One of the most studied mechanisms controlling RNA turnover is nonsense-mediated decay (NMD). It eliminates erroneous transcripts containing premature termination codons (PTC), and also regulates expression of functional transcripts in condition-dependent manner. Recently, my host lab has demonstrated existence of widespread coupling between mRNA decay and translation. This opens a new window for translation dependent regulation of RNA turnover. Specifically, recent studies show that ribosomal frameshifts (RF) occurring during translation induce PTCs and fire NMD response. Preliminary evidence from the host lab suggests that RF is regulated upon stress and could serve as a new mechanism to sense environmental signals and adapt mRNA concentrations. It is yet to be tested if such a regulation is of widespread nature in the cell. The main goal of this project is to investigate stress-dependent regulation of ribosomal frameshifts and their role in RNA turnover. The 5PSeq approach developed in the host lab will allow for performing high-scale analysis in yeast and human cells, and overcoming existing technological challenges previously limiting research in the field. This project will also explore the cross-talk between RNA turnover and telomere maintenance in cellular response to stress and aging. This will expand the accumulated evidence suggesting interconnection of RNA turnover with other processes involved in cellular adaptability. Finally, I will develop a software package for analysis of RNA degradation datasets that can be used by the research community.

Mots clés : rna degradation, nonsense mediated decay, ribosomal frameshifts, stress, telomere maintenance, ageing, sequencing data analysis software

Participants :
- Karolinska Institutet (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191852.16 €
Projet MEANN (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Molecular Electronics Artificial Neural Networks (MEANN) will adapt for the first time a recurrent neural network (RNN) to address complex multivariate correlation questions that arise in single molecular break junction (SMBJ) experiments. The hypothesis is that a RNN will be better than a human at identifying relationships between nanoscopic geometry changes of the junctions and the measured variables in SMBJ data sets, with little or no human bias. These improvements in the data analysis approach will allow researchers to address many of the present problems in SMBJ research, most notably reproducibility and bridging the theory-experiment gap. The proposal has three objectives to implement this goal. I will: (1) generate simulated SMBJ data and use this simulated data to train a RNN to sort SMBJ data into classes with unique and significant features in the data; (2) measure large sets of experimental data while on secondment and apply the trained RNN to the experimental data to sort the experimental data into the classes the RNN has already identified in the simulated data; and (3) derive a deeper understanding of the relationships between the physical processes involved in the break junction, and the observable variables of the experiment. MEANN maximizes my development as a researcher by exposing me to three important opportunities: (1) a world class theoretical chemistry group where I will learn computational and management skills necessary for my future as a researcher, (2) new experimental physics techniques while on secondment, and (3) planning an Applied RNN Summit where I will network with industry leaders in RNN development, share my expertise with peers, and prepare teaching materials to introduce my research to students. As a result of MEANN, researchers will have new tools to generate simulated SMBJ data, analyse their experimental data quickly and objectively, and answer important questions in condensed matter physics and physical chemistry.


Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet SpliceCore (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

More than 95% of human genes undergo pre-mRNA splicing, and alternative splicing of mRNA precursors represents a prevalent mode of gene regulation. Errors in this process are often the origin of of disorders. Most of splicing-related diseases are caused by perturbation in pre-mRNA transcripts which lead to their aberrant processing. Interestingly, a fraction of mutations affecting directly splicing factors, including core spliceosomal components, has been linked to a group of pathologies. Particularly intriguing are variants of the key spliceosomal subcomplex U4/5/6 tri-snRNP, associated with Retinitis Pigmentosa. Why these mutations lead to highly tissue-specific phenotypes, rather than general toxicity cause by a global block in splicing, remain unexplained. The proposed research aims to increase our understanding of the molecular mechanisms underlying the effects of these mutations and shed light on the basis of the disease. To functionally dissect these variants, I will combine spliceosomal network approaches (I) with genome-wide transcriptome analysis (II) and detailed biochemical and structural studies (III). Mechanistic insights derived from these analyses will help to identify transcripts that are predominantly sensitive to these mutations and that could be behind their pathogenic effects (IV). This work will allow us to better understand the function of key splicing factors, as well as the basis for their effects on splice site selection and their contributions to Retinitis Pigmentosa pathology.

Mots clés : splicing, mutations, core splicosome

Participants :
- Centre for Genomic Regulation (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet OE-ILAC (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

More than half of the worldwide population (55%) is overweight or obese (O/O), while the increasing trends are leading to shorten life expectancy. Tackling O/O is a European priority, and innovative actions to achieve this are urgently needed: no country has so far succeeded in reducing its growth. O/O are related to several axes of social inequality, such as socioeconomic status, gender, ethnicity, age, and place of residence. O/O are more frequent in more unequal societies and increase with urbanisation. The highly urbanised Iberia-Latin American region has strong historical, political, economic and cultural bonds. However, this region has also considerable heterogeneity in the degree of social and gender inequalities (SGI), urbanisation, and in the prevalence of O/O. Thus, this transnational scenario holds great potential for the analysis of the urban SGI in O/O. The overall objective of this project is to develop an analytical model to assess the determinants of SGI in O/O in the Iberia-Latin American cities over a recent time period, and to inform urban policies by integrating interdisciplinary, intersectional and intersectoral approaches. A mixed methods study design will be applied, with a cross-sectional multi-city study followed by a public policy analysis and the development of recommendations for polices and interventions to address SGI in O/O. A gender perspective will be adopted throughout all the action. The novel integration of these approaches will contribute to tackling urban SGI in O/O by providing a more comprehensive understanding of its drivers and by finding new avenues for improving equity-based urban policies. The project will also provide insights to reshape O/O as a systemic problem worldwide. Moreover, the action will have a key impact on my career development, on the institutions involved, and on relevant target audiences (researchers, practitioners, policy makers) as well as on the wider community.

Mots clés : social inequality, gender inequality, obesity, public health, public policies, social determinants

Participants :
- Pompeu Fabra University (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160932.48 €
Projet LGCMOT (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Motivation -the process that facilitates overcoming the cost of effortful actions to attain desired outcomes- is key to achievement and well-being. Importantly, there are major individual differences in motivational levels. Low motivation can reflect states of fatigue or depression not only in patients, but also in the general population, and there is currently no effective treatment to ameliorate this condition. Understanding the brain mechanisms linked to variation in motivated behavior will be of utmost importance to advancing treatments. Brain metabolism in the ventral striatum -a brain’s motivation hub- is emerging as a strong regulator of motivated behaviors. Strong pilot data from the host lab has underscored a striking correspondence between glutathione (GSH) - the most prominent antioxidant – levels in the ventral striatum and motivate on the prediction of effort-based motivated behavior. However, solid evidence is still lacking. The goal of this proposal is to determine whether GSH levels in the ventral striatum relate to widespread levels of effortful performance in healthy human subjects. To this end, I will use a combination of high-field (7T) 1H-Magnetic Resonance Spectroscopy (1H-MRS; to quantify GSH levels in the ventral striatum, and in the occipital cortex as control region), functional Magnetic Resonance Imaging (fMRI; focusing on BOLD activity in the ventral striatum), behavioral testing for physical and cognitive effort-based motivation, and computational modeling (allowing to dissect specific motivational components). In addition, a 7-days nutritional intervention (N-acetyl-cysteine or placebo) to manipulate the GSH system will be tested for its effectiveness to 1) increase striatal GSH levels; and 2) improve specific aspects of motivated behavior (e.g., incentive valuation, effortful performance) in the physical and/or cognitive effort tasks. Therefore, LGCMOT outcomes will greatly advance knowledge in the emerging field of neurometabolism.

Mots clés : motivation, glutathione, n acetyl cysteine, spectroscopy, neuroimaging

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191149.44 €
Projet AmygdalaNeuroMod (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Proper neuronal circuit function depends fundamentally on the balance of neuromodulators, a set of neurotransmitters released widely throughout the brain. Almost every mental disorder, including anxiety and depression, that affect one out of four Europeans, are associated with a neuromodulatory imbalance in specific sub-circuits. Elucidating the role of different neuromodulatory inputs to specific brain regions holds the keys to understanding and treating mood disorders. The amygdala plays an essential role in the processing of emotional stimuli and salience, ranging from reward to threat and synaptic alterations in this region are critical for learning and emotional processing. Amygdala is innervated by every major neuromodulator, yet surprisingly little is known about the activity of these inputs under physiological conditions and how neuromodulation regulates amygdala circuit activity during different behavioral states and learning. Here, I propose to study the functional role of neuromodulatory inputs to the amygdala circuitry during learning and decision-making. Towards this goal, I will combine my experience in large-scale electrophysiology with the expertise of the host laboratory in modern genetic tools and neurotechnologies to simultaneously record and manipulate the activity of dopamine, serotonin, norepinephrine and acetylcholine inputs to the amygdala during context-guided decision-making in behaving mice. Using this approach, I aim to characterize the logic of interactions between neuromodulators and its implementation at the level of defined circuits and cell types in the amygdala and to demonstrate the role of this coordination in defining network activity, behavioral state and learning. The fellowship will contribute to our basic understanding of the interplay between two core brain systems, while it will provide me with a unique opportunity to expand my expertise and establish the foundations of my future career as an independent group leader.

Mots clés : neuromodulation, amygdala, learning and memory, neuronal circuits, optogenetics, behavior, dopamine, serotonin, norepinephrine, acetylcholine, decision making, reward, context, emotion, fear

Participants :
- Friedrich Miescher Institute (Suisse) — Coordinator, beneficiary, Recherche, subvention : 191149.44 €
Projet HEAfilmonMg (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Protective high entropy alloys (HEA) thin films/coatings on Mg substrate will be produced by mechanical alloying (MA), cold spraying (CS) and post-surface laser annealing (SLA) process. By using variable but controlled MA process and CS coating parameters (HEA feedstock powder & HEA MAed powder characteristics, CS technology geometric parameters, CS deposition parameters), variations in the micro-structure and property in HEA coatings will be attained. Microstructural characterization of HEA feedstock powders, MAed powders, CS coatings and CS+post-SLA coatings will be carried out by SEM, TEM, XRD, porosity measurements. Wear, oxidation, corrosion tests, hardness and elongation measurements will be made to determine chemical and mechanical properties of coatings. With this way relationships among deposition parameters-microstructure-properties will be determined in addition to the feasibility study of producing protective (wear and oxidation resistant) HEA coatings on Mg-parts by combined MA+CS & post- SLA process.

Mots clés : hea film on mg parts, mechanical alloying, cold spray, laser surface annealing, materials characterization

Participants :
- Trinity College Dublin (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196590.72 €
Projet PCAGED-KI (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protein kinases play a critical role in a number of cellular processes, including cell proliferation, differentiation and apoptosis. Recently, the aberrant regulation of lymphocyte-specific protein tyrosine kinases (LCK) has been associated with the over activation of microglia cells (important immune effector cells that reside in the central nervous system, CNS) and in turn, the development of Alzheimer’s disease (AD). Unfortunately, the detail of LCK's dynamic function and the importance of quantitative, spatial and time-dependent parameters regarding microglia activation is poorly understood. As such, the ability to manipulate LCK activity using light would result in temporal control of enzymatic activity, thus serving as a valuable approach to probe the function of LCK in microglia cells and in turn, further our understanding of AD and related neurodegenerative disorders. While such studies cannot be performed using conventional LCK inhibitors, this project aims to control the enzymatic activity of LCK by the development of a stimuli-responsive release-and-report system, through the introduction of a photolabile 'caging' moiety onto a fluorescent kinase inhibitor. The caging group will also consist of an appropriate ‘quencher’, quenching the innate fluorescence properties of the inhibitor through energy transfer (FRET). Exposure to light (> 320 nm) will result in decaging of the prodrug to give the active form, while simultaneously switching ‘on’ the fluorescence — reporting back to the user that the compound has been activated. To demonstrate the potential of the release-and-report kinase inhibitor as a tool to probe LCK function in microglia cells, confocal microscopy will be employed to visualise the site of microglia activation and the time frame during CNS development in zebrafish model systems.

Mots clés : photocaging, spatio temporal control, fluorescence

Participants :
- University of Gothenburg (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173857.2 €
Projet MEMBRANEPROT (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protein-protein tridimensional (3D) structures are fundamental for structural biology and drug discovery. Many docking algorithms were developed for that purpose, but they have limited accuracy in generating native-like structures and identifying the most correct one, particularly in the case of membrane proteins such as G-protein Coupled Receptors (GPCRs). In order to deal with these complex systems and overcome the limitations of existing software, we will develop and optimize computational approaches and construct novel combinations of mature methodologies, to serve in the study of membrane proteins in general. In particularly, we will focus in: i) improving the search and scoring algorithms for the docking process of membrane proteins, ii) developing software to accurately predict the high-order oligomers interfacial residues, and iii) constructing a docking algorithm able to predict their 3D oligomeric structure. Our new approaches will be applied to a relevant biological system: the dopamine receptor type 2 (D2R), a typical member of Class A GPCRs involved in many cognitive, emotional and motor functions. D2R acts by ligand-dependent signalling through two major systems: the G-proteins, and the Arrestin proteins (Arr-s). How ligands determine the preference for one or the other is not yet understood at the molecular level, and this precludes both the characterization of pathway selectivity and the design of biased ligands. More importantly, the physiological relevance of oligomerization for this process is still topic of vigorous debate. Therefore, building on both my unique expertise and Prof. Bonvin well-known impact in methodological development, this project will yield novel methods and approaches to serve in the study of membrane protein systems and their functional mechanisms, benefiting the entire research field. It will also provide truly new fundamental knowledge and insights into the selectivity of D2R signalling.

Mots clés : docking algorithms, search, scoring, methodological development, protein interactions, mutagenesis, gpcr

Participants :
- Utrecht University (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 177598.8 €
Projet DYNAMO (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Proteins embedded in cell membranes are vital signaling and trafficking platforms connecting the outside to the inside of a cell, and functioning as primary drug targets. DYNAMO is an integrative dynamic structural biology project, with the ambitious goal of developing and implementing comprehensive experimental and computational approaches for studying the structural dynamics of membrane receptors (MRs) and their complexes at native-like conditions. DYNAMO is highly interdisciplinary, combining protein chemistry and computational physics to study dynamical processes underlying the function of MRs, and is designed to combine the expertise of the fellow and host. The project will establish an integrated platform based on the nanodisc-technology and the combined use of low- and high-resolution structural biology techniques to bring unique and alternative insights into the structural dynamics of MRs containing ”fuzzy” (i.e highly flexible) domains, and the role this plays in functional signaling assemblies. In order to broaden the scope of the project and secure a general applicability of the developed methodology, full-length tissue Factor (TF) and Ghrelin receptor (GHS-R1a) are selected as models of single-pass and multi-pass MRs. These MRs do not only display different topologies and functional assemblies but also different selectivity towards lipids. TF and GHS-R1a are central to blood coagulation and energy homeostasis, respectively, and also connected to genetic and metabolic disorders, and thereby not only relevant as model systems but also promising drug targets. The project will exploit the recent advances in SAXS/SANS- and NMR-based methods to study the TF and GHS-R1a in nanodiscs, with an emphasis on their conformational ensemble nature. Upon the establishment of the methodology, it will be extended to study the interaction with their endogenous ligands.

Mots clés : tissue factor, gpcrs, conformational dynamics, membrane mimics, nanodisc technology, integrative structural biology, biomolecular nmr, neutron and x ray scattering

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €