Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Membrane proteins – development of new computational approaches and its application to G-Protein Coupled Receptors (MEMBRANEPROT)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Chemistry
Countries involved: Netherlands
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2014, 2014)
Start date: 2016-03-01
End date: 2018-02-28
Duration (months): 24.0
Total project cost (EUR): 177598.8
EU funding (EUR): 177598.8
Participants: 1
Project status: 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.

Keywords: docking algorithms,search,scoring,methodological development,protein interactions,mutagenesis,gpcr
The ABC of Cell Volume Regulation (ABCvolume)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced grants
Action type: ERC actions
Panel: Molecules of Life: Biological Mechanisms, Structures and Functions
Panel description: Molecular biology, biochemistry, structural biology, molecular biophysics, synthetic and chemical biology, drug design, innovative methods and modelling
Countries involved: Netherlands
Call: ERC Advanced Grant (ERC-2014-ADG, 2014)
Start date: 2015-07-01
End date: 2020-06-30
Duration (months): 60.0
Total project cost (EUR): 2247230.68
EU funding (EUR): 2247230.68
Participants: 1
Project status: CLOSED

Cell volume regulation is crucial for any living cell because changes in volume determine the metabolic activity through e.g. changes in ionic strength, pH, macromolecular crowding and membrane tension. These physical chemical parameters influence interaction rates and affinities of biomolecules, folding rates, and fold stabilities in vivo. Understanding of the underlying volume regulatory mechanisms has immediate application in biotechnology and health, yet these factors are generally ignored in systems analyses of cellular functions. My team has uncovered a number of mechanisms and insights of cell volume regulation. The next step forward is to elucidate how the components of a cell volume regulatory circuit work together and control the physicochemical conditions of the cell. I propose construction of a synthetic cell in which an osmoregulatory transporter and mechanosensitive channel form a minimal volume regulatory network. My group has developed the technology to reconstitute membrane proteins into lipid vesicles (synthetic cells). One of the challenges is to incorporate into the vesicles an efficient pathway for ATP production and maintain energy homeostasis while the load on the system varies. We aim to control the transmembrane flux of osmolytes, which requires elucidation of the molecular mechanism of gating of the osmoregulatory transporter. We will focus on the glycine betaine ABC importer, which is one of the most complex transporters known to date with ten distinct protein domains, transiently interacting with each other. The proposed synthetic metabolic circuit constitutes a fascinating out-of-equilibrium system, allowing us to understand cell volume regulatory mechanisms in a context and at a level of complexity minimally needed for life. Analysis of this circuit will address many outstanding questions and eventually allow us to design more sophisticated vesicular systems with applications, for example as compartmentalized reaction networks.

Keywords: membrane transport,cell volume regulation,membrane reconstitution,synthetic cell,abc transporter,osmoregulation,mechanosensitive channel,molecular sensor
Competition for Space in Development and Diseases (CoSpaDD)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Cellular, Developmental and Regenerative Biology
Panel description: Structure and function of the cell, cell-cell communication, embryogenesis, tissue differentiation, organogenesis, growth, development, evolution of development, organoids, stem cells, regeneration, therapeutic approaches
Countries involved: France
Call: ERC Starting Grant (ERC-2017-STG, 2017)
Start date: 2018-01-01
End date: 2023-06-30
Duration (months): 66.0
Total project cost (EUR): 1489147.0
EU funding (EUR): 1489147.0
Participants: 1
Project status: SIGNED

Developing tissues have a remarkable plasticity illustrated by their capacity to regenerate and form normal organs despite strong perturbations. This requires the adjustment of single cell behaviour to their neighbours and to tissue scale parameters. The modulation of cell growth and proliferation was suggested to be driven by mechanical inputs, however the mechanisms adjusting cell death are not well known. Recently it was shown that epithelial cells could be eliminated by spontaneous live-cell delamination following an increase of cell density. Studying cell delamination in the midline region of the Drosophila pupal notum, we confirmed that local tissue crowding is necessary and sufficient to drive cell elimination and found that Caspase 3 activation precedes and is required for cell delamination. This suggested that a yet unknown pathway is responsible for crowding sensing and activation of caspase, which does not involve already known mechanical sensing pathways. Moreover, we showed that fast growing clones in the notum could induce neighbouring cell elimination through crowding-induced death. This suggested that crowding-induced death could promote tissue invasion by pretumoural cells. Here we will combine genetics, quantitative live imaging, statistics, laser perturbations and modelling to study crowding-induced death in Drosophila in order to: 1) find single cell deformations responsible for caspase activation 2) find new pathways responsible for density sensing and apoptosis induction 3) test their contribution to adult tissue homeostasis, morphogenesis and cell elimination coordination 4) study the role of crowding-induced death during competition between different cell types and tissue invasion 5) Explore theoretically the conditions required for efficient space competition between two cell populations. This project will provide essential information for the understanding of epithelial homeostasis, mechanotransduction and tissue invasion by tumoural cells

Keywords: mechanotransduction,morphogenesis,cell competition
The Dynamic Impacts of Child Health and Skills Enhanced by School Interventions across the Life Course (DYNAMICS)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Economic Sciences
Countries involved: Denmark
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2022-04-20
End date: 2025-04-14
Duration (months): 24.0
Total project cost (EUR): 207312.0
EU funding (EUR): 207312.0
Participants: 1
Project status: SIGNED

This project, “The Dynamic Impacts of Child Health and Skills Enhanced by School Interventions across the Life Course” (DYNAMICS), is the first ever to rigorously and comprehensively study complete short- and long-term dynamic effects of health and human capital at school ages. It combines research in the fields of economics and epidemiology to answer the overarching research question: whether and how the dynamics of a child’s health and skills, enhanced by successive nationwide school reforms, translates into various later-life outcomes. Economists have recently shown that public health interventions in early life substantially boost an individual’s earnings in the long term, albeit have not investigated how these effects emerge. Moreover, epidemiologists have found that body size, growth and disease history at school ages are strongly associated with health in adulthood. DYNAMICS investigates how the interplay of school health, nutrition, and education reforms as well as the event of WWII, which uniquely overlapped in Denmark, affected children and how it formed their health and well-being in adulthood. It combines the most recent advances in research through the University of Southern Denmark’s expertise in health dynamics and advanced econometric methods, the University of Copenhagen’s expertise in life course epidemiology, my research experience with individual data and early-life effects, and the richest data on Denmark. This project will not only create societally important cutting-edge knowledge in applied microeconomics but also immensely broaden my international network and provide important transferable skills for future success.

Keywords: school based health intervention,human capital formation,long term socioeconomic effects,dynamic interactions
Efficient Computational Methods for Active Flow Control Using Adjoint Sensitivities (KAFKA)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Information Science and Engineering
Countries involved: United Kingdom
Call: Individual Fellowships (H2020-MSCA-IF-2018, 2018)
Start date: 2020-09-01
End date: 2022-08-31
Duration (months): 24.0
Total project cost (EUR): 224933.76
EU funding (EUR): 224933.76
Participants: 1
Project status: CLOSED

Active Flow Control (AFC) mechanisms have tremendous potential in improving flow characteristics in a wide variety of sectors. For effective AFC design, it is essential to determine the sensitivity of each of the control parameters to the flow property of interest. Adjoint methods provide the sensitivity of the objective function to any number of input parameters at a reasonable additional cost. They are based on simple RANS turbulence modelling, which captures poorly the physics of flow especially in the presence of complex flow features such as flow separation, which can be effectively eliminated by flow control. Recently developed Reynolds Stress Models (RSM) display significant improvement in the flow prediction capacity as compared to conventional RANS models, yet adjoints with RSM are not yet available. An alternative for accurate flow prediction is Large Eddy Simulation (LES). Unfortunately resolving the chaotic turbulent motion results in exponential growth of the gradients. Our first objective is to develop an effective discrete adjoint method with an accurate and stable RSM, and compute sensitivities in complex flows involving active control mechanism applied to realistic wing geometries. Although RSM outperforms conventional turbulence models in a host of applications, there is a need for further physics-based calibration for specific flows. Our second objective is to use the adjoint method to drive the model coefficients to their optimum value such that the model results match with high-fidelity simulation data yielding a better turbulence model, which can be applied for effective flow control design in bluff body with severe rear flow separation. Our third objective will be to develop adjoint approaches for chaotic LES flows using the hosting groups' innovative gappy checkpointing approach that retains the accuracy of the LES but regularises the chaotic motion for the reverse adjoint pass, hence avoiding the exponential blowup of the sensitivities.

Keywords: active flow control,adjoint optimisation,rans modelling,large eddy simulations
Biogenicity of Martian Materials: critical assessment of biosignatures based on chemolithoautotrophic interactions (BIOMAMA)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Universe sciences
Panel description: Astro-physics/-chemistry/-biology; solar system; planetary systems; stellar, galactic and extragalactic astronomy; cosmology; space sciences; astronomical instrumentation and data
Countries involved: Austria,France
Call: ERC CONSOLIDATOR GRANTS (ERC-2020-COG, 2020)
Start date: 2022-05-01
End date: 2027-04-30
Duration (months): 60.0
Total project cost (EUR): 1999746.0
EU funding (EUR): 1999746.0
Participants: 2
Project status: SIGNED

The search for biologically driven alterations on Mars and its potential as habitat for past or present life is a primary aim of the upcoming Mars exploration missions. While a range of environments that would have been well suited to support a potential chemolithotrophy on Mars have been proposed, our understanding of putative biosignatures to be targeted in Martian materials is still poor. A valuable source of information can be extracted from microbial fingerprints of chemolithotrophic life based on Martian materials (Martian meteorites, regolith simulants). Chemolithotrophic microorganisms employ an astonishing number of metabolic pathways to extract energy from diverse inorganic electron donors/acceptors, shaping global biogeochemical cycles. Using a holistic approach based on laboratory, field and space exposure experiments, we propose to investigate interactions of Earth’s various chemolithoautotrophs with Martian materials. The bottom-up exploration of mineral-microbial interactions for different chemolithotrophs cultivated on Martian materials as the sole energy sources, will decipher mineral and metabolic biosignatures associated with these cases. This project explores unique microbial interactions with extraterrestrial materials down to the nanoscale and atomic resolution utilizing a comprehensive toolbox of cutting-edge techniques. BioMaMa will identify preservable biomarkers/biosignatures of chemolithotrophic life on Martian materials after the exposure to simulated Martian conditions at low Earth orbit and ground-based facilities. A complex approach will be used to investigate meteorite-microbial interactions in Mars-analogue sites on Earth. The extensive knowledge gained from BioMaMa will help to understand and critically interpret the results of future Mars exploration missions (ExoMars 2020). These studies will lay the foundation for efficient nanoanalytical spectroscopy of returned Mars samples, to critically assess their potential biogenicity.

Keywords: mars,meteorites,space missions,extremophiles,chemolithotrophs,biominerals,biosignatures
Single-Cell Transcriptomics and Spliceosome analysis to uncover new mechanisms of neuronal vulnerability to Huntington’s Disease. (TransSplicHD)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Reintegration panel
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Italy
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2015, 2015)
Start date: 2016-09-01
End date: 2018-08-31
Duration (months): 24.0
Total project cost (EUR): 180277.2
EU funding (EUR): 180277.2
Participants: 1
Project status: CLOSED

Huntington’s disease (HD) is neurodegenerative disease caused by a CAG repeat expansion mutation in the HTT gene. The pathological process, which ultimately leads to neuronal loss mainly in the caudate and putamen, is induced - in a truly dominant manner - by a single copy of the mutant allele. Transcriptional deregulation has becoming a prevailing feature in HD and changes at single-gene level in RNA biogenesis and aberrant alternative splicing (AS) events have been associated to neuronal vulnerability. Here, I propose to disentangle at genome-wide level the connections between mutant huntingtin expression and RNA processing, and its implications for neuronal vulnerability to death. Specifically, I propose to study alterations in RNA transcription and AS in: Aim 1. Striatal, cortical and cerebellar areas of Hdh knock-in (KI) HD accurate mouse models through global RNAseq; Aim 2. In specific medium spiny neurons (MSN) of the Drd1 or Drd2 direct and indirect pathways of Hdh KI striatum through laser capture dissection and single-cell RNAseq. The present research proposal represents a synthesis of my interest, expertise in RNA regulation, genome-wide approaches and single-cell analysis in the context of neurodegenerative disorders with my most recent exposure to human genetic. On the other hand, at the CIBIO host institution I will greatly benefit from the scientific exchange with the PIs of the neurobiology area, and my supervisor in particular, whose skills in neuroscience, neuroanatomical and behavioral analyses will perfectly blend and consolidate my cellular and molecular expertize. Thus, I believe I am optimally positioned to accomplish the aims of the current application: the MSCA-RI-IF will be instrumental to develop this initial hypothesis into deeper biological understanding of HD and represent a crucial support to my scientific integration as a competitive, woman investigator in the transition from postdoctoral training to an independent academic career.

Keywords: huntington s disease,expanded cag trinucleotide repeat,rnaseq,single cell transcriptomics,alternative splicing,medium size spiny neurons
Twice as Hard, Half as Good? Women Candidates’ Experience of Sexism on the Campaign Trail (TWICEASGOOD)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced grants
Action type: ERC actions
Panel: The Social World and Its Diversity
Panel description: Sociology, social psychology, social anthropology, education sciences, communication studies
Countries involved: Spain,Türkiye,Netherlands,United Kingdom,United Kingdom,United Kingdom,United Kingdom
Call: ERC ADVANCED GRANT (ERC-2020-ADG, 2020)
Start date: 2022-01-01
End date: 2026-12-31
Duration (months): 60.0
Total project cost (EUR): 2499998.0
EU funding (EUR): 2241473.96
Participants: 7
Project status: SIGNED

How does sexism affect women’s pathway to political office? Scholars have claimed that voter sexism is over because women candidates win elections at the same rate as men. However, the emergence of a gender equality backlash, misogynistic social media campaigns and the continued under-representation of women in political office globally, indicate a need to re-examine whether sexism acts as a barrier to women’s representation. To better understand political representation, therefore, it is important to understand how and under which conditions sexism by voters, media and political parties, actual and anticipated, can lead women candidates to alter campaign behavior and strategies. For the proposed programme of research in TWICEASGOOD, we reconceptualize the “gender penalty” faced by women candidates to take into account the sexism, threats of violence that they face online, through social media, in the traditional media and in face-to-face encounters. We aim to understand the extent of these types of sexism as well as the ways in which women candidates anticipate and counter them, by being “twice as good”, in order to achieve electoral success. To better understand how encounters of “everyday sexism” on the campaign trail, both online and offline and in the media, shape women’s campaign efforts and chances at electoral success, we propose an ambitious five-year programme of research that captures candidate experiences of sexism and assesses their impact on electoral outcomes. To capture how sexism is experienced “everyday” on the campaign trail, we used a mixed-methods approach, bringing together participant-observation of candidates on the campaign trail in four countries with quantitative media analysis, candidate surveys and a battery of items administered in Round 11 of the European Social Survey to create a cross-national sexism index. This rich data will generate new insights about the causes of women’s continued under-representation in politics.

Keywords: women,elections,campaigns,sexism,violence against women in politics,representation,social,media,news media,communication,attitudes