Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet LIGER (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer cells heavily rely on the proteasome-ubiquitin system mediated tuning of proteins stability and proteome composition. Proteasome and ubiquitin ligases targeting drugs are already in use against certain haematological cancers, and similar inhibitors are currently explored as a possibility for autoimmune diseases and parasite infestation treatment. E3 ubiquitin ligases are the ultimate target for these therapies as they determine specificity in substrate recognition. It is thus of utmost interest for both basic and translational research to find new ubiquitin ligases essential for cell proliferation, cell migration or cancer progression and couple them with their substrates. In the proposed LIGER project, we aspire to fuse cutting-edge methods to identify new ubiquitin ligase – substrate pairs. In particular, we will focus on E3 ubiquitin ligases involved in cancer progression and more specifically, in its two crucial aspects - cell growth and cell migration. To pre-select the ubiquitin ligases for further analysis, we will perform an unbiased screen for ubiquitin ligases that are involved in cell growth and cell migration. To achieve this goal, CRISPR library screening methodology will be employed. Consequentially, we will purify proteins associated with the selected ubiquitin ligases and identify their potential substrates. Standard biochemical and molecular biology methods will allow us to study in detail the protein interface between the ubiquitin ligases and their novel substrates and describe the biological function of their degradation. LIGER project will increase our understanding of ubiquitin pathway in physiological and pathological conditions and identify new potential targets for cancer therapy.

Mots clés : cell cycle, therapeutic target, ubiquitin ligase, proteasome, substrate, cancer

Participants :
- Czech Academy of Sciences (Rép. Tchèque) — Coordinator, beneficiary, Recherche, subvention : 154720.8 €
Projet GlyCANswer (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer continues to be the most formidable challenge in modern medicine and the second leading cause of deaths worldwide. However, in recent years, the treatment of unresectable cancer has undergone a paradigm shift with the advent of immunotherapy. Yet, despite the great progress in the field, the majority of cancer patients still do not respond to any of the available immunotherapeutics and no reliable biomarker exists to predict those patients that would benefit from it. In order to facilitate the development of new strategies for immunotherapy, and to identify improved predictive biomarkers for treatment response, the GlyCANswer project envisions to elucidate how the cancer glycoproteome dictates the immune response. The GlyCANswer project aims to unravel the interplay between the cancer cell glycoproteome and immune recognition in the two most frequent malignancies worldwide, namely lung and breast cancer. By using a combination of cutting-edge glycoproteomics, glycomics and immune profiling approaches in innovative mouse models and cell culture systems, the GlyCANswer project will 1) map the immunomodulatory glycosylation of cancer cells 2) explore the detailed mechanisms of glycan-mediated immune regulation 3) identify new biomarkers and provide new therapeutic targets for immune therapy.

Mots clés : glycosylation, cancer model, immunology, glycoproteomics, immunotherapy

Participants :
- Austrian Academy of Sciences (Autriche) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 174167.04 €
Projet CHyMERA (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Cancer heterogeneity is reflected in the multitude of phenotypes found in the clinic, with different proliferation statuses and metastatic potentials. These features cannot be assessed with the molecular imaging methods commonly available for diagnosis and monitoring. The main goal of this proposal is to develop a molecular imaging methodology based on endogenous contrast – CHyMERA – and demonstrate its feasibility to image hotspot areas of active proliferation and metastatic potential. The approach is based on the concept of cancer metabolic plasticity, does not require contrast agents or radioactive tracers, and should ultimately provide more specificity to cancer diagnosis and treatment planning than other imaging methods currently available. We propose to use animal models of human cancer, a glucose-enhanced imaging method, and an objective analysis of regional metabolic responses to controlled, reversible changes in the tumour microenvironment (perturbations), such as transient hypoxia. Specifically, we will (i) develop and validate CHyMERA at ultra-high magnetic fields, to monitor the metabolic kinetics of glucose and lactate in the tumour microenvironment. This methodology will be (ii) applied in vivo to two immunocompetent mouse model of GBM (allograft and genetically engineered models), to image vascular permeability/perfusion and hotspots of glioma proliferation. Finally, we will (iii) carry out a pilot study with two isogenic mouse models breast of cancer, metastatic and non-metastatic, to generate hotspots maps of proliferation and metastatic potential. All in vivo results will be validated post-mortem by immunohistochemistry. If successful, this methodology has a strong potential for clinical translational, which the host institution is ideally suited to test.


Participants :
- Champalimaud Foundation (Portugal) — Coordinator, beneficiary, Recherche, subvention : 159815.04 €
Projet Need2immune (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer immunotherapy, defined as the ability to mobilise the host’s own immune system to kill cancer, has recently within the last 5 years, taken a central role within mainstream oncology. This period has seen the field rapidly accelerate towards unprecedented clinical responses in patients, and the development of novel classes of immunotherapeutic drugs. One approach has been to design more personalised immunotherapies along with new methods in delivering the therapeutic cargo. It is anticipated that this will play a defining role for cancer immunotherapy in terms of how to better achieve sustained remissions or complete eradication. One of the challenges in the future will be to understand how to administer these molecules since the current approach of systemic administration harbours the risk of causing serious toxicity and/or autoimmunity. This could drastically lower the serum levels of immune reagents needed with a decrease in adverse effects and lower risk of autoimmune reactions, without losing systemic efficacy. Currently, cancer immunotherapies are injected into the bloodstream but systemic injections have many drawbacks. It could be more effective therefore to inject this kind of therapy locally and directly to target tumour cells. This proposal will be to implement a more direct approach, where the immunotherapy's effects could be more easily controlled, with also the possibility for lower doses to be administered. Recently, microneedles have been attracting attention as new drug delivery tools. The microneedle has already been shown to be a highly effective intradermal and transdermal vaccine delivery method due to its mechanism of action, painlessness and ease of use. The goal is therefore to use microneedles to deliver localised doses of combination immunotherapies, e.g. vaccine with checkpoint modulators, in nanoparticles, as the focus of a novel approach to developing new strategies for the trackable delivery of onco-immunotherapeutic agents.

Mots clés : personalized cancer vaccines, high throughput formulation screening, liposomes, neo antigens, synthetic long peptides

Participants :
- Tecodevelopment gmbh (Allemagne) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 162806.4 €
Projet CRISTONE (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer is responsible for 8.5 million deaths worldwide each year, representing a considerable burden for society. In cancer cells, tumor repression genes are deactivated by epigenetic mechanisms. The accessibility of DNA to transcription factors is determined in part by the chemical modifications of histones, proteins that pack DNA into condensed chromatin. When histones are deacetylated by histone deacetylases (HDACs), the chromatin structure is even more packed, preventing gene expression. HDAC inhibitors are epigenetic drugs currently in the market, able to increase histone acetylation, unpacking DNA for gene transcription. However, the specific mechanisms leading to the success or failure of those drugs are poorly understood, leading to unpredictable therapeutic outcomes. HDAC inhibitors are expected to interact with HDACs in the cell nucleus. However, fluorescence-labeling has revealed HDAC inhibitors to locate mostly outside the nucleus in living cells, suggesting that their genomic effects represent only part of their activities. This project aims at developing a set of tools, using a modified genome-editing method and a fluorescent chemical probe combined with genome-wide assays to understand specifically the genomic mechanisms of HDAC inhibitors. We will develop the CRISTONE (CRISPR-based HDAC inhibitor targeted to histones) tool to allow targeted HDAC inhibition. We will target an HDAC1 inhibitor (a histone tail peptide) specifically to repressed loci in the genome of HDAC1-overexpressing HEK 293T cells. To understanding the transcriptional consequences of targeted and untargeted HDAC1 inhibition, the CRISTONE effects will be compared to those of a new fluorescent chemical probe capable of inhibiting nuclear HDACs. To assess the cellular phenotypic outcome, we will test the genome-wide cellular effects on transcription and chromatin accessibility, giving insights into the specific effects of genomic, targeted HDAC inhibition.

Mots clés : hdac inhibitor, crispr, chromatin remodeling, histone acetylation, chemical probe, epigenetic targets

Participants :
- Yeshiva University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Geneva (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 265840.2 €
Projet PreCaFit (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Cancer is the second leading cause of death worldwide, accounting for 18.1 million new cases and 9.6 million deaths in 2018, and representing the highest economic burden to modern health care systems with ~$1.16 trillion per year. Exploration of gender or race disparity in cancer susceptibility has not been common practice. Together with cancer, cardiometabolic disease are the largest contributors to the burden of chronic disease worldwide. Every year many cases of cancer seem attributable to metabolic disease. Growing evidence has firmly established that both low fitness and physical inactivity are strongly associated with many chronic conditions and all-cause mortality. Therefore, there is an urgent need to unravel whether fitness and physical activity are related to cancer. The PreCaFit project will fill the gaps in the knowledge examining the relationship between fitness, physical activity and cancer. Further, to ensure the scalability of the results, we will examine the effects of exercise on cancer biomarkers. This will produce a large impact in science and society since it will provide the first step toward feasible, effective and safe prevention strategies. The use of objective measurements and a unique set of techniques for data acquisition, the epidemiological collection in a large sample, the lab research at Stanford University (Prof. Myers), the secondments in Europe at Prof. Ekelund lab for learning data pooling and harmonization techniques, and at Prof. Riboli lab for learning about cancer epidemiology and biomarkers, and the pilot randomized controlled trial on exercise and cancer biomarkers at UGR (Prof. Ortega) place this project in pole position to address how lifestyle behaviours might mitigate cancer. To do so, the training, management skills, dissemination/exploitation and communication/outreach activities in the top-level hosts and secondment institutions ensure the scientific excellence and determination with improved career possibilities.

Mots clés : physical activity, physical fitness, adults, randomized controlled trial, non communicable diseases, reference standards, race, cardiometabolic disease

Participants :
- University of Granada (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 245732.16 €
- Stanford University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet ISAC (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer patients are increasingly surviving their disease, but disparities in cancer outcomes still persist, and even widen, for some groups of patients. This is the case for older adults as they have not benefitted from the improvements in cancer diagnosis and treatment at the same magnitude as their middle-aged counterparts. Older adults account for the largest proportion of cancer diagnoses, and with the number of diagnoses expected to double in two decades such disparities will result in substantial amount of years of life lost due to unfair age-related disparities in cancer survival. The ISAC project thus aims to investigate the role of comorbidities and other factors in cancer survival disparities among older patients compared with younger patients, which will aid interventions to increase the probability of survival regardless of age. Dr Sophie Pilleron will have the opportunity to be trained at the highest possible level, extending her knowledge in comorbidities and health disparities research in the University of Otago, and her knowledge in colon and lung cancer in the THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD. She will also extend her transferable skills (e.g. grant writing, oral communication, and student supervision), which are necessary for a successful career as an independent researcher. Finally, the results of the ISAC project will be disseminated and communicated to the scientific community, policy makers and the general public through a range of activities. For example, the findings of the project will be disseminated through high-impact publications and presentations at international conferences, and the Fellow will directly present her research to policy makers. She will also target non-specialists through media outlets, social networking services, online videos, or presentations at science festivals in order to facilitate the translation of the findings and their related implications to a non-scientific audience.

Mots clés : cancer, survival, older adults, disparity, population based study

Participants :
- University of Otago (Nouvelle-Zélande) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Leeds (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 201275.52 €
Projet RoNDBioCan (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer represents one of the main causes of death in the European Union (WHO). Particularly, non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is the leading cause of cancer-related death worldwide. Despite significant therapeutic improvements, the survival rate of patients with advanced stage NSCLC remains dismal, signifying a critical need to elucidate the molecular processes driving NSCLC. Inflammasomes are major drivers of inflammatory responses and are deregulated in a wide range of disorders, yet their participation in carcinogenesis is largely unknown. Genome analyses reported that the NLRP3 receptor, component of the NLRP3 inflammasome, is affected by somatic alterations in 20% of NSCLC. Moreover, recent evidence has shown that NLRP3 is essential for the activation of the ATM/CHK2 pathway in response to double strand breaks (DSBs), while its expression is systematically absent in NSCLC cells. Based on these data, we hypothesize that NLRP3 is a key factor in the DDR pathway to DSBs and in the maintenance of genome integrity in lung epithelial cells, and as a consequence may play a key tumor suppressor role. The objectives of RoNDBioCan will be to decipher the molecular mechanism of NLRP3 function in the DDR pathway and to evaluate the therapeutic potential associated with NLRP3 expression. By characterizing novel NLRP3 partners and examining the impact of NLRP3 re-expression on tumor development in vivo, RoNDBioCan will significantly improve the current knowledge regarding NLRP3 participation in lung cancer. Given that the poor outcome associated with NSCLC is mostly due to limited curative options, there is an urgent need to identify new biomarkers and additional treatments to reduce the current burden of lung cancer. This work will thus considerably contribute to the development of new effective and personalized therapeutic approaches to help improve the prognosis of lung cancer patients.

Mots clés : nlrp3 receptor, non small cell lung cancer, dna damage signaling, biomarker

Participants :
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
- Université Claude Bernard - Lyon 1 (France) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet OFF-GROUND (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Statut du projet : SIGNED

Carbonate platforms are geologically complex 3D structures. Their hydrogeology has been investigated via conceptual models, sand box experiments and numerical models. Most of these models are hypothetical, 2D in nature, and based on simplistic assumptions on flow processes and geological characteristics. Recently, topographically-driven meteoric groundwater has been proposed as a key player in driving fluid circulation in carbonate platforms, both onshore and offshore. This project is dedicated to building representative 3D geological and hydrogeological models of offshore freshened groundwater in the Malta Plateau, to specifically address the following questions: what is the 3D geometry, scale and rate of fluid circulation in carbonate platforms, at present and during sea level lowstands? What are the main controlling factors? What are the key processes driving fluid circulation in carbonate platforms, at present and during sea level lowstands? What is the role played by topographically-driven meteoric groundwater? Addressing these knowledge gaps is important for the future use of offshore freshened groundwater as a source of potable water, and provide insights into diagenetic processes. During this research I will have the possibility to widely expand my geoscience knowledge, from Oil & Gas to Water, too, both during the time I will spend working at University of Malta, as host organization, as well as during my secondment c/o Geomar, in Germany. I will dedicate myself to disseminate the results of my research through specific planned actions, and I expect to mature a CV and a research experience strong enough to allow me to start a new carrier in the academic/research world in the near future, based on my previous experience in the industry and on the new skill I will learn.

Mots clés : offshore fresh groundwater, carbonate aquifers, malta platform, mediterranean, fractured and karstified carbonate reservoirs, hydro geological model, 3d modelling

Participants :
- University of Malta (Malte) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160049.28 €
Projet DisparFam (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The first union formation and the birth of the first child are among the most critical events shaping men’s and women’s life-course trajectories. Sustainable Development Goals (SDG) stress that all individuals should have access to means that allow them to control their fertility and should be able to marry at an age that does not harm their development capabilities. Central to SDGs is eradicating disparities in the timing of family formation, yet the understanding of their global patterns and determinants is limited, particularly in low- and middle-income countries (LMICs). This is a critical research gap as many women in LMICs enter their first union and become mothers very early in life and much earlier than men, which puts them at risk of adverse health outcomes. Focusing on 69 LMICs this project aims to radically improve our understanding of global family changes by providing novel empirical evidence on a critical yet poorly understood topic. Namely, using nuanced indicators, I will deliver the first-ever global examination of changes in disparities in the timing of family formation, both within and between the populations of women and men. Subsequently, I will investigate the role of an under-research dimension of education - schooling quality – and the role of gender inequality in opportunities in driving these disparities. This project will straddle the disciplines of demography, sociology, and international development to produce cutting-edge research that will improve the scientific understanding of social inequalities. By delivering novel evidence about the role of educational and gender inequalities in shaping young adults’ family formation trajectories, this project will be of value to the wider research and policy community, including organizations such as the UN. It will inform public policy on causes and solutions to critical global problems affecting millions of individuals worldwide, such as very early marriage, parenthood, and gender inequalities.

Mots clés : family formation, low and middle income countries, gender inequality, education, survey data

Participants :
- CERCA Institution (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €