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

G protein coupled receptors (GPCRs) are key regulators of cell homeostasis. Given their importance in cell physiology, they have been extensively exploited as drug targets. Despite this, many discordant observations on receptor signalling and on GPCR drug response remain unexplained. Changes in receptor expression in different human tissues can be a key contributor to such differences in GPCR behaviour. And still, no comprehensive study has characterized human GPCR transcriptomics and its impact on receptor function. Such an analysis could help answer fundamental questions on GPCR pharmacology such as: How are different receptor types distributed across human tissues and how does this affect receptor function? How does age and gender-related GPCR differential expression affect receptor pharmacology? And how does splice variant distribution in different tissues influence receptor signalling? In this project, I will address these questions by applying a computational biology approach combining publicly available transcriptomics data with information on receptor structure, intracellular coupling, and pharmacogenomics. This will allow obtaining for the first time a GPCR-wide distribution map across human tissues; determining how differential expression according to age and gender can affect GPCR function; and assessing the impact of alternative splicing on receptor integrity, regulation, and coupling. At the end of this project, these insights will be made publicly available to the research community through the development of a web resource associated with the widely-used GPCR database. Using such a multidisciplinary approach, the proposed analysis will help clarify the importance of different receptor transcriptional profiles in cell physiology and drug response, point to more relevant systems to study GPCR signalling and to characterise new drug candidates, and foster a more personalised medicine by considering expression variability in the general human population.

Mots clés : gpcrs, structural biology, molecular pharmacology

Participants :
- UK Research and Innovation (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 212933.76 €
Projet NECESSITY (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

G protein-coupled receptors (GPCRs) represent the largest family of cell surface proteins involved in signal transmission. Nearly 30% of human cancers harbor mutations in GPCRs/G proteins. Activating mutations in GNAQ and GNA11 have been discovered in 90% of Uveal Melanoma (UM).UM is the most common primary cancer of the eye in adults and to date there are no effective treatments. 50% of UM patients develop metastatic disease, which is refractory to current chemotherapies leading to patient death within a year. Prolonged Gaq signaling leads to the activation of YAP, a transcriptional co-activator regulated, necessary for UM growth. GNAQ stimulates YAP through FAK. Inhibition of FAK reduces UM growth,leading FAK to be a potential therapeutic target for UM. In UM, the particular Gαq–regulated pathways that when overactive can render FAK inhibitor(FAKi) ineffective, as well as what feedback mechanisms should be targeted to optimize therapeutic responses to FAKi are still unknown. I will use a panel of GNAQ-driven UM cells and perform a genetic screen using the Cancer Signaling Toolkit to discover molecular determinants of sensitivity or resistance to FAK inhibition. Signaling candidates and screening hits discovered will be prioritized and their biological impact in UM growth and FAKi sensitivity will be evaluated. To increase FAKi activity and reduce therapy resistance, I will also investigate whether co-targeting candidate GNAQ-effector and FAKi resistance pathways will synergize with FAKi, resulting in UM cell death. Finally,I will explore the mechanism of UM cell death by co-targeting. My studies will reveal new targeted(precision) strategies for multiple Gαq-driven pathological conditions in cancer The project will be supervised by Dr. Gutikind and Dr.Martini two experts in GPRC/G proteins. Through this work, I aim to broaden my scientific expertise (including technical and transferable skills) and to establish myself as an independent researcher in cancer biology

Mots clés : uveal melanoma, cancer, cell signaling, screening, g proteins and, or gpcr, drug, resistance, precision therapy

Participants :
- University of Pisa (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 269002.56 €
- University of California System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet GASGOLD (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

GASGOLD aims for the development of efficient Au(I)-catalysed methodologies for the challenging intermolecular synthesis of important monomers, oligomers and polymers of acetylene gas. Au(I)-catalysts allow for the formation of cyclopropyl Au(I)-carbenes after reaction with an alkyne and alkene. The carbenes are reactive towards rearrangement to form 1,3-dienes, which are important building blocks for a range of natural and other important products, such as synthetic rubbers. Preliminary results show that further reaction of certain 1,3-dienes with acetylene can occur, forming oligomeric derivatives and this reactivity will be harnessed and further exploited in this project. Initially, the development of an effective protocol for the synthesis of a wider range and more challenging substituted 1,3-dienes from acetylene gas, both in monomeric and oligomeric forms, will be established. The reaction mechanism determining the configuration of the alkenes will be studied, for example by kinetic monitoring and isolation of reaction intermediates, to explain the observed selectivity, potentially synthesise other isomers and improve on the reaction conditions and catalyst design. The initial results will inspire the challenging selective expansion of 1,3-dienes with acetylene to form substituted 1,3,5-hexatrienes. Additionally, the unprecedented use of both acetylene and ethylene gas in Au(I)-catalysis will be explored for the synthesis of polyacetylene derivatives, which are highly important materials with electrical conductivity, as well as in the purification of ethylene gas. The development of this project offers an innovative solution for the long-standing problem of utilising acetylene gas as a simple building block in Au(I)-catalysis, offering a clear advantage over the current state-of-the-art of the field. Furthermore, the expected synergistic performance between the experienced researcher and the host group, will maximise the potential for success of the project.

Mots clés : au i  catalysis, acetylene oligomerisation and polymerisation, alkyne and alkene activation

Participants :
- Institut Català d'Investigació Química (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet H. Pylori-Scopy (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Gastric Cancer (GC) is the fifth most common malignancy in the world. Being the third leading cause of death, it claimed 723,000 lives worldwide in 2012, 12 lives/day in the UK (2014-2016), 29 lives/day in U.S. in 2018 and 6th most common in Europe. With such high number of deaths, it can be compared to no less than an epidemic disease. According to International Agency for Research on Cancer, 89% of all GC cases are attributed to infection from Helicobacter Pylori (Hp). H. pylori produces an enzyme called urease which causes creation of an alkaline buffer zone which keeps it safe from gastric acid and silences the immune system of stomach against this microbe. This result in formation of gastric ulcer which grows into cancerous tumour. Early diagnosis of H. pylori is important for understanding pathology of gastric cancer and starting early therapy. But high cost, ambiguous diagnosis and poor patient engagement of existing diagnostic methods leads to late/advanced stage diagnosis of cancer. Patients spend $700-$1800 for standard 2 week triple drug therapy. Such high cost in low and middle income country (LMIC) is a burden where 33 million individual face catastrophic health expense & cancer take their toll at the cost of human life. This cost can further increase with late diagnosis. H. Pylori-Scopy aims to reduce the cost by performing early diagnosis with single stop, easily accessible, portable, unambiguous, instantaneous screening device, which results in increased patient engagement with no waiting for medical reports and quick medication. H. Pylori-Scopy is a combination of light based Raman/Fourier Transform Infrared, & Chitosan-Magnetic-Swob spectroscopy, which offer an unambiguous addendum tool for h-pylori diagnosis using standard endoscopy, suitable not only for in-theatre but also for portable/accessible use in the LMIC regions. H.Pylori-Scopy integrates all three techniques into an endoscopic device which will work with low-cost robotic control.

Mots clés : gastric cancer screening, smart medical tools

Participants :
- University of Leeds (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet GenALMA (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

GenALMA aims to offer novel perspectives and invaluable new data on kinship and the development of urban space by examining late medieval Genoa, one of the most socially vibrant cities during the foundational phase of contemporary Europe. It will investigate: 1) why and how aristocratic families chose to unite in a peculiar form of association which had long-lasting repercussions across the city’s social spectrum, eventually involving families and individuals of lesser social standing; 2) the impact of the construction of such solidarities and alliances, and the patrimonial strategies these entailed, on the reconfiguration of the city’s residential and architectural landscape. By tackling these two main questions, GenALMA will address issues related to the development of kinship structures and gender roles, the evolution of patrimonial rights, the networks of socialisation, and the changes in the urban fabric. Employing an innovative interdisciplinary methodology, the project will involve the management (through multiple databases) of large data sets collected from still unexplored and exceptional historical sources (notarial records of Genoa) which will be used to reconstruct kinship ties and to map out residential patterns thanks to cutting edge technology available at the host institution. The digital maps will represent an unprecedented attempt at charting the evolution of the urban fabric over the span of three centuries. The project will be conducted at the CNRS – Centre Roland Mousnier where the candidate will benefit from high level interdisciplinary training offered by the host institution, which will improve her skills in analysing historical data, and from the presence of several specialists with whom to discuss methodological and historiographical approaches. So as to reach the widest audience possible, the results of the project will be disseminated via conferences and workshops, a monograph, publications in high level scholarly journals, and a blog.

Mots clés : 12th 15th centuries, family history, urban topography, north central italian communes, medieval aristocracy, history of genoa

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 196707.84 €
Projet Bioinformatics4Breeding (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Genetic selection for high yielding dairy cows has been associated with reduced fertility. Infertility remains the major reason for culling, decreasing longevity and reducing production efficiency. We propose that this trend could be reversed by identifying key genes involving reproductive function and selective breeding of more longlasting cows. The specific research objectives are: 1) to train the incoming researcher in bioinformatics methodologies related to analysis of large genomic datasets including SNP detection, genotyping, and evolutionary conserved DNA elements detection; 2) to use the methodologies to analyse dairy phenotypic and genomic data to highlight potential genic and regulatory regions of the cattle genome containing polymorphisms which are beneficial, with a particular focus on fertility; 3) to use appropriate tools to investigate the likely effects of both coding and regulatory variants on the expression of the candidate genes found in these regions; 4) to use pathway analysis to understand how the candidate genes may influence key molecular events and larger gene networks involved in reproductive phenotypes; 5) to recommend appropriate selection procedures to the EU dairy breeding industry to supplement current genomic methods. The project combines the expertise of Consiglio per la Ricerca in Agricoltura e l’analisi dell’Economia agraria, Italy (CREA) and the Royal Veterinary College, UK (RVC) in farm animal genetics and genomics and dairy cow production. The objectives will be met by the mobility of Dr L Buggiotti to the UK, where she will work closely alongside two senior RVC scientists, Dr DM Larkin and Professor DC Wathes. She will transfer this expertise back to CREA on her return. Both groups are experienced in knowledge transfer to the dairy industry and are committed to use the information generated to breed more fertile cows, so improving longevity and promoting sustainability of the EU dairy industry.

Mots clés : breeding, fertility, dairy cows

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet EvolInfome (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Genome-scale sequence data play an important role across the biological, medical, and agricultural sciences for extracting the signatures of divergence among species and populations. Multiple basic biological forces influence the evolutionary information content of genomes, leading to substantial variation across genomic loci and lineages. Models of molecular evolution for phylogenomics are routinely used for extracting information about evolutionary history, and ultimately for making inferences of the relationships and amount of evolutionary change among taxa. However, existing phylogenomic methods are not amenable for identifying the impact of specific drivers of historical information across whole genomes. The present action will develop tests in the framework of model adequacy for assessing the impact of the primary evolutionary forces on the genome. Assessment of model adequacy proceeds by comparing simulated data under a given evolutionary model with empirical data. The novel framework will be tailored at whole-genome analysis. It will allow a comprehensive examination of the sources information signal left by basic evolutionary forces, such as speciation, mutation, selection, recombination, and drift. The new methods will be disseminated through an intuitive software package that will be openly available for researchers across biological sciences. Examining the sources of evolutionary information will allow improved phylogenetic inferences and guide model improvement. An unparalleled genomic resource of the genomes of every avian family, soon to be released by the host, will be examined in detail with the methods developed. This will provide insights into genome evolution in birds and inferences of their evolutionary history with unprecedented confidence.

Mots clés : molecular evolution

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 219312.0 €
Projet GenoPri (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Genomic data carries a lot of sensitive information about its owner such as his predispositions to sensitive diseases, ancestors, physical attributes, and genomic data of his relatives (leading to interdependent privacy risks). Individuals share vast amount of information on the Web, and some of this information can be used to infer their genomic data. Hence, there is a need to clearly understand the privacy risks on genomic data of individuals considering publicly available information on the Web. It is also crucial to protect genomic privacy of individuals without compromising the utilization of genomic data in research and healthcare. The two main objectives of this project are (i) to develop a new unifying framework for quantification of genomic privacy of individuals and (ii) to establish a complete framework for privacy-preserving utilization, sharing, and verification of genomic data under real-life threat models. Graph-based, iterative algorithms previously developed by the applicant to efficiently analyze big data and make inference from it will be the foundation for the new quantification framework. To achieve the holistic genomic privacy objective, cryptographic tools, techniques from information theory, and statistics (differential privacy) will be used. This project will be a significant step towards understanding the privacy risks on genomic data of individuals and protecting the privacy of genomic data. It will also provide a new vision for security and privacy of health-related data in general and will find many implications in other domains such as banking and online social networks. The results of the project will also have an impact on future policies and legislation about protection of health-related data. This EF will have big impact on the future career of the applicant by helping him build new connections, enhance his expertise, increase his visibility in the field of security and privacy, and improve his independent research skills.

Mots clés : genomic privacy, privacy enhancing technologies

Participants :
- Bilkent University (Turquie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 157845.6 €
Projet THERMCP (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Geobacillus spp are thermophilic Gram positive bacteria which are specialists in the degradation of hemicellulose derived from renewable biological feedstocks and the supervisor’s group has recently engineered strains able to degrade cellulose. Some of the strains are facultative anaerobes which can grow anaerobically and produce fermentation products such as lactate and ethanol. Hence they are an ideal platform for producing fermentation products from renewable carbohydrate resources, such as lignocellulose. Recent genome sequencing has shown that some strains have the ability to produce proteinaceous micro-compartments, known from other organisms to host reactions which produce unstable/highly reactive intermediates, and these have been observed by EM analysis in the lab of the supervisor. In this project the MC fellow will exploit some novel technology under development in the lab of the supervisor to develop thermostable alpha-keto acid decarboxylases, which are not typically present in thermophiles. These produce reactive aldehydes which cause toxicity to producing cells, even in the presence of a cognate alcohol dehydrogenase, but this can potentially be reduced by targeting the decarboxylase and alcohol dehydrogenase to a protein micro-compartment. Therefore, the aim of this project is to establish the rules for targeting enzymes to protein micro-compartments in Geobacillus spp and exploit these using thermophilic decarboxylase – dehydrogenase combinations to produce 1) ethanol, 2) isobutanol. The final constructs will be evaluated against real lignocellulosic feedstocks in the lab of the industrial collaborator ReBio Ltd. The project will provide an in depth training in metabolic and cellular engineering, employing synthetic biology strategies.

Mots clés : metabolic engineering, protein compartments, protein targeting, renewable energy

Participants :
- University of Bath (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet OMNICS (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Geologic Carbon Storage (GCS) is a promising remedial activity that society can use to tackle imminent problems from increased atmospheric CO2 and climate change. The fate and transport of the stored CO2 are controlled by a storage formation’s petrophysical parameters, which evolve rapidly after the CO2 injection because of geochemical reactions. Knowing how the pore structure evolves is critical to the safe and effective implementation of GCS because it affects the sealing integrity, injectivity and storage capacity of a geologic site. How such evolution can be quantified is still unknown, because of the technological difficulties in direct observation within pores and the high computational cost required to predict such evolution based on current modelling approaches. My project will pioneer the study of GCS-related petrophysical parameter evolution by combining synchrotron based nanotomography with a highly customizable reactor network model. Tomography enables the in situ observation of the porous media’s morphological evolution that leads to petrophysical property changes. The reactor network model can significantly reduce computational costs for predicting parameter evolution. OMNICS builds on a combination of my expertise in GCS-related research and chemical reactor design with my host’s world leading nanostructure characterization facilities and cutting edge interdisciplinary research profile. Strong industry links provided by my host means that my new prediction technique will provide direct guidance for site selection, risk assessment and injection management, pushing the technological readiness level of GCS from applied research towards market relevant implementation as a technical support service. Meanwhile, the training, mentoring and support offered by my advisor, Prof. S. Stipp, will broaden my expertise, sharpen my competences and extend my research network, which will help me secure a academic position in Europe by fully realizing my potential.

Mots clés : emergent processes, evolution of petrophysical parameters, computerised tomography, chemical reactor modelling, geochemical reactions, geologic carbon storage

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €