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

Antibiotics are essential for treating bacterial infections. However, antimicrobial resistance (AMR) has spread among pathogenic bacteria, leading to therapy failure or deaths of patients. Due to their association with promiscuous mobile genetic elements, clinically important antibiotic resistance genes (ARGs) can spread rapidly among diverse bacteria through horizontal gene transfer (HGT). Due to HGT, identifying the microbial hosts of the ARGs in an ecosystem is a challenge. Importantly, it has been shown that ARGS can spread from human gut commensals to clinical pathogens and vice versa. Wastewater from clinical sources can importantly select for HGT of ARGs between different microbes, as both antibiotics and ARGs are present at high levels. The aim of this project - "ARCS" (Antibiotic Resistance in Clinical Sewage microbiomes), is to reveal the ARGs exchange networks in clinical sewage microbiomes. The research objectives are: 1) Link ARGs to microbial hosts by using novel culture-independent methods based on DNA high-throughput sequencing. 2) Link ARGs to mobile genetic elements by isolating, sequencing, and characterizing the genomes of the identified hosts of ARGs. 3) Evaluate whether the isolates can transfer their ARGs to clinical pathogens using conjugation assays. ARGS will thus lead to a step-change in our understanding of HGT of ARGs in complex microbial ecosystems. The Fellow Dr. Lisandra Zepeda's expertise in generating and analysing DNA sequencing data and the host Prof. Willem van Schaik's international leadership in AMR ensure a successful completion of ARCS and a favourable knowledge transfer for both parties. Furthermore, the supportive environment of the University of Birmingham ensures the accomplishment of the Fellow's training in crucial areas such as microbial DNA capture sequencing, microbiology laboratory techniques, and mentoring skills. Thus, ARCS will enable Dr. Zepeda to realise her career goal of becoming a research group leader.

Mots clés : antimicrobial resistance, metagenomics, genomics, microbiology, clinical sewage microbiome, horizontal gene transfer, antibiotic resistance gene, clinical pathogen

Participants :
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet NSFTA (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Antibody-Drug Conjugates (ADCs) are revolutionary next-generation therapeutics. The number of ADCs in the clinic is constantly growing with four of them having now reached the market. Despite this great promise, the complex structure of antibodies results in drawbacks for their reliable modification to construct ADCs, thus impairing the full potential of ADCs. One of the major reasons for clinical failure is that it is hard to control the drug to antibody ratio (DAR) to obtain homogeneous structures. Furthermore, current synthetic methods give access to ADCs with a DAR limited to values of 2, 4 and 8, thus lowering the variety of species being tested and possibilities to balance their toxicity. Hence, new synthetic methods giving access to homo- or hetero-functional ADCs with a high control of the DAR would be tremendous progress; being highly impactful to the ADC field and related patient outcomes. Here, we propose innovative methods to functionalise antibodies. Based on a well-established, patented disulfide bond re-bridging method, and orthogonal click ligations, we will finely control antibody modification. This will yield: 1) Mono-functional ADCs with highly controlled DAR, including odd DARs (DAR 1, DAR 3...). This is fundamental to determine the optimal ratio between drug loading and hydrophobicity to obtain the best therapeutic activity. 2) Hetero-functional ADCs with controlled amount and site of functionalisation with different payloads. This includes production of DAR 1+1, DAR 1+1+1…several combinations of payloads are possible, paving the way to promising multi-therapies. 3) Fully synthetic bi-specific antibodies. Our method provides an unprecedented way to obtain bi-specific antibodies in a controlled and adaptable fashion from native antibodies, i.e. without requiring bioengineering. The project addresses unmet needs in the therapeutic antibody field and could bring unprecedented outlooks to this booming sector.

Mots clés : antibody drug conjugate  adc, antibody modification, drug antibody ratio  dar, organic chemistry, thiol re bridging, click chemistry, bispecific antibody, therapeutic application

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet PregnancyAD (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Antidepressants are the mainstay of pharmacological treatment for depressive and anxiety disorders in the perinatal period, and up to one in ten pregnant women take them. Among these women, over 50% discontinue antidepressants during pregnancy due to fear of possible adverse fetal effects. However, discontinuation may increase the risk of relapse, which can also have profound negative impacts. Evidence on perinatal relapse risk following antidepressant discontinuation during pregnancy is sparse and limited to highly selected populations. Moreover, the only factors considered in studies so far have been simple demographics and clinical features, while genetic profiling is conspicuously absent. The project aims to address knowledge gaps which urgently need to be understood in order for clinical care to provide personalized antidepressant treatment recommendations around pregnancy. This overarching objective will identify women at low or high relapse risk after discontinuing antidepressants during pregnancy and determine risk factors of relapse to enable personal risk estimates for the first time, in a large representative population, combining demographics, clinical features and genetic data retrieved from Danish national registers and the Integrative Psychiatric Research (iPSYCH) cohort. The project will provide a unique opportunity due to its multidisciplinary nature and innovative combinations of genetics and epidemiology. The proposed research will benefit from the expertise in genetics, genomics, and psychiatric epidemiology of the supervisors, and the fellow’s multidisciplinary skills in epidemiology and biostatistics applied on large, highly complicated datasets. The fellow will acquire state-of-the-art skills in the analysis of genetic data, planning, and management by training-through-research along with coursework. This project will form a fundamental leap towards her future independent career as a leading and international recognized epidemiologist.

Mots clés : antidepressant treatment, polygenic, genetic risk score, relapse, reproductive epidemiology, pharmacoepidemiology, psychiatric epidemiology, pregnancy, perinatal, population based study, cohort study

Participants :
- University of Queensland (Australie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Aarhus University (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 201392.64 €
Projet DIMAF (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Antiferromagnetic materials are very promising candidates for the development of new data storage devices with a low power comsumption, which explains the recent growing interest for the field of antiferromagnetic spintronics. However, the study of these systems is hindered by the difficulty to image their magnetic state in real space with most of the available microscopy techniques. The recently developed nitrogen-vacancy (NV) center magnetometry appears to be a solution to this problem. It probes the magnetic order via the measurement of the stray field present at the surface of the sample. The field is measured using the Zeeman shifts of the electronic spin sublevels of a single nitrogen-vacancy defect in diamond. The single NV defect is placed at the apex of a nanopillar in a diamond tip integrated into an atomic force microscope, allowing to scan in close proximity to the sample surface. The goal of this project is to use this technique to explore the magnetic order at the nanoscale in antiferromagnetic materials which are relevant for applications in spintronics. The magnetic configuration of the modulated antiferromagnet BiFeO3 will be investigated. The experiments will first focus on the effects of epitaxial strain on the antiferromagnetic order. In a second step, the antiferromagnetic structure will be manipulated with local strain and spin currents. The NV-center magnetometer will be used to image directly the induced modifications. This project offers high-quality technical training in NV-center magnetometry as well as the opportunity to acquire and strengthen transferable skills and to participate to international collaborations. It will thus foster the career development of the researcher in the growing and highly innovative field of antiferromagnetic spintronics.

Mots clés : nitrogen vacancy center in diamond, scanning probe microscopy, quantum sensing

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 184707.84 €
Projet SaPhaDe (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Antimicrobial drug resistance is a serious global threat that make us to fear the return of the mortality rates from pre-penicillin times. A promising alternative to antibiotic drugs is the phage therapy, which is based in viruses that kill bacteria. The rational design of effective phage therapeutics requires a fundamental understanding of evolutionary co-adaptation of phages and bacteria. These co-adaptations have led to the development of multiple anti-phage defence systems in bacteria which modulate their susceptibility to be killed by phages at strain level. In this way, the study of the diversity and mechanisms of action of defence islands in bacterial pathogens represents crucial knowledge for improving rapid delivery of phage-based therapeutics. The proposed work aims to deeply characterize the anti-phage defences in a human pathogen, Salmonella, to provide the strategy to discover and classify phage counter-defences for an optimal design of phage therapy. This project will characterize the genetics population of Salmonella to study the distribution and diversity of anti-phage defence islands and will validate the activity and function of the defence and counter-defence in bacteria and phage, respectively. The experienced researcher (ER) will establish a collaborative link between the laboratories of laboratories of Dr. German Bou (Spain), who has extensive experience in clinical microbiology and genetic modification methods, and Prof. Martin Polz (USA), who is a world expert in the ecology and evolution of environmental microbiology. This collaboration will allow to perform the most advanced methods in population and comparative genomics, isolation and discovery of phages, large scale phage host range assays and genetic modification of bacteria. The data generated in this project will be essential to understand the anti-phage defence mechanisms and to improve clinical decisions to maximize the efficacy of phage therapeutics.

Mots clés : salmonella, bacteriophages, defence islands, comparative genomics, mobilome, phage therapy, antibiotic resistance, bioinformatics

Participants :
- Fundacion profesor novoa santos (Espagne) — Coordinator, beneficiary, Recherche, subvention : 245732.16 €
- Massachusetts Institute of Technology (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet PACEMech (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Antimicrobial resistance is recognised as one of the greatest threats to human health worldwide. Multidrug efflux pumps play a major role in the development of drug resistance in bacterial pathogens. These pumps are able to actively export remarkably broad collections antibiotics and biocides out of the cell. Multidrug efflux pumps have classically been organised into five distinct families or superfamilies. Due to their importance, representative proteins from each of these families have been extensively studied. Using a combination of functional genomics and biochemical methods to study antimicrobial resistance in the hospital pathogen Acinetobacter baumannii, I recently identified AceI, the founding member of a sixth family of multidrug efflux pumps called the Proteobacterial Antimicrobial Compound Efflux (PACE) family. The PACE family is the first new family of efflux pumps to be described in 15 years. In light of its recent identification, there is a paucity of fundamental data describing how PACE family pumps mediate drug efflux. This proposal will apply in vitro biochemical, biophysical and structural analyses to reveal molecular details of the structure and functional transport mechanism operating in PACE family pumps. This proposal will draw on the diverse collective expertise of my Fellowship Supervisor Prof Peter Henderson and his expert colleagues in membrane protein structural analyses and biophysics. In conducting this research I will build lasting collaborative links with these experts that will extend beyond the duration of this fellowship. I will receive specialised training in powerful membrane protein analysis methods that are essential to my career goal of establishing a leading research laboratory examining membrane transport proteins, from regulation to molecular mechanisms. My laboratory vision is to develop novel strategies to interfere with drug efflux pump function and so overcome resistance conferred by this important class of proteins.

Mots clés : antimicrobial resistance, multidrug efflux, membrane transport

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

Antimicrobials have saved millions of lives since they were first discovered. Unfortunately, today the world is facing up a global antibiotic resistance health emergency. In fact, bacterial infections which have been susceptible to standard antibiotic regimes for decades are now becoming resistant to all major antimicrobial treatments, making their efficacy undermined. Within this context, this proposal aims to develop a new and original strategy to combat antimicrobial resistance. Photopharmacology is a novel and emerging medical approach which exploits light to modulate the activity of drugs. The energy of light, which is not toxic to humans and easily delivered with high precision, can be used to change, at will, the conformation and chemical properties of drugs, making them more selective and efficient. This project wants to apply the photopharmacology concept to amphiphilic lipid drugs, namely those molecules bearing a polar head and a lipid tail acting as antimicrobials through disruption of bacterial membranes. Since, unlike other proteins and enzymes, membranes cannot mutate, they are ideal targets to combat antimicrobial resistance. New Photoswitchable Amphiphilic Lipis (PALs), able to intercalate the bacterial membranes, will be developed and synthesised by inserting a photoactivable probe into a amphiphilic lipid. Upon light irradiation, these PALs will change conformation leading, selectively, to membrane damage and consequent cell death. A set of 20 PALs will be synthesised and the compounds will be evaluated against a panel of bacteria, alone or in synergistic combination with other antibiotics. Preliminary in-vivo studies on Galleria models will be carried out as well as NMR-metabolomic studies to elucidate the key interactions of PALs with living systems and the response of bacteria to the action of these new drugs. The data generated through this project will create new means and opportunities in the fight against bacterial resistance.

Mots clés : photopharmacology, antimicrobial resistance, antibacterials, drug discovery, nmrmetabolomic

Participants :
- University of London (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 61246.85 €
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 151686.91 €
Projet RAC (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Antioxidants, by neutralizing ROS and ROS-induced DNA damages, are thought to protect against cancer. Recently this common view was challenged by the observation that antioxidants may accelerate tumor progression in mouse models of lung cancer, by turning down the DNA-damage-gH2AX-p53 signaling pathway. This study raised new questions: Are antioxidants able to induce metastasis from benign tumors, by silencing p53 expression? Are cytosolic ROS equivalent to mitochondrial ROS for lung cancer progression? In a first part, I will test the hypothesis that antioxidants favor the metastatic process in lung cancer in state-of the art mouse models. I will administer NAC or vitamin E in the drinking water or the diet of the mice (Kras2LSL) after tumor initiation, and define their impact on metastasis and survival. Preliminary data showed that antioxidants are able to induce metastasis in this non-metastatic model. RNA from tumors and metastases of antioxidant-treated and control mice will be used for RNAseq to identify molecular events that accompany the antioxidant effect. These experiments should allow me to answer my hypothesis and provide new leads on the metastatic process of lung cancer. Lung cancer is indeed a metastatic disease that is still challenging to treat and in great need of new treatments. In a second part, I will investigate the impact of mitochondria-targeted antioxidant (mitoQ, a quinone targeting the inner membrane of the mitochondria) in order to specifically assess the role of mitochondrial ROS on tumor progression. I will administer mitoQ in the drinking water of mice after tumor initiation, and assess its impact on tumor progression. These experiments will allow me to determine whether mitochondrial ROS are pro-tumorigenic, as we hypothesize. Altogether this project will undoubtedly deepen our knowledge of the importance of ROS and ROS scavenging in tumors and will generate a treasure trove of hypotheses for future studies. .

Mots clés : lung cancer, antioxidants, reactive oxygen species, mouse models

Participants :
- University of Gothenburg (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173857.2 €
Projet GLUTORHIV (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Antiretroviral therapy can decrease HIV-1 below the limit of detection but fails to eliminate the virus completely. One of the main goals of a HIV-1 vaccine is the generation of cytotoxic CD8 T cell responses that counteract the virus. CD8 T cells participate in the control of viremia early but progressively show weakened functions, which leads to loss of virus control. HIV controllers are a rare group of infected patients who can control the virus for years without antiretroviral therapy. CD8 T cells from HIV-controllers display an outstanding capacity to eliminate infected CD4 T cells ex vivo but the underlying mechanisms are still not understood. Preliminary data aiming at establishing a single cell transcriptional signature associated with control of HIV suggest an important role of the mTOR pathway during the chronic stage. This pathway plays a major role in glucose metabolism and CD8 T cells cytotoxic function. This raises the hypothesis that the extraordinary HIV-suppressive capacity of HIV-controllers CD8 T cells is associated with the modulation of mTOR pathway and glucose metabolism. This project aims to 1) Study the single cell gene expression of HIV-specific CD8 T cells in HIV patients longitudinally from acute to chronic stages and understand the factors linked to control and loss of function of CD8 T cells during disease progression. 2) To characterize the role of mTOR pathway in the ability of CD8 T cells from HIV-controller to eliminate infected cells and test if this pathway can be modulated to fine-tune anti-HIV CD8 T cells responses. 3) To understand if an optimal glucose metabolism is necessary for CD8 T-cells suppression of HIV and if this capacity can be improved by increasing available glucose. This work will help to understand the characteristics of effective CD8+ T cell responses against HIV and may guide the development of anti-HIV vaccines or immunotherapies to induce HIV controller-like responses in HIV-infected progressors.

Mots clés : hiv cd8  t cells responses, hiv controllers, mtor, glucose metabolism, single cell gene expression

Participants :
- Institut Pasteur (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet AnxNPS (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Anxiety disorders are one of the most prevalent and chronic forms of psychiatric disorder. Critically, these disorders often have an early onset, with childhood and adolescence being the core period of developmental risk. Anxiety in this period can lead to academic and socio-emotional difficulties, as well as long-term mental health problems. Elucidating the developmental trajectories and aetiology of early anxiety is therefore of great importance. This project aims to further understanding of the neurobiological and psychological mechanisms through which anxiety emerges and is maintained across childhood and adolescence, as well as how atypical early social experience may increase risk. Multi-model techniques (neuroimaging, cognitive assessment, behavioural observation) incorporating interdisciplinary insights will be utilized to realize the following objectives in a longitudinal study of rhesus macaques varying in early social experience: 1) assess levels of anxiety over time; 2) track brain development over time and relate to concurrent and future anxiety; 3) assess attention bias to threat (ABT) over time and investigate its relationship with brain development and anxiety; and 4) consider effects of atypical early social experience on relationships between brain development, ABT and anxiety. Novel aspects of this project include the longitudinal investigation of brain development across the core period of risk for anxiety disorders, and consideration of how atypical early experience might modulate relationships between brain development, ABT, and anxiety. Project results will provide a more in-depth and nuanced understanding of early anxiety, which can be used to guide future human research and aid the design of more effective treatments and early interventions. Advanced training in neuroimaging and nonhuman primate behaviour will expand the candidate’s skill-set significantly, establishing their trajectory towards becoming an independent research leader.

Mots clés : anxiety, early development, childhood and adolescence, neuroimaging, attention bias, early social experience, behavioural observation

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 196707.84 €