Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet NeuroADHD (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, with 5% of children and 2.5% of adults being affected. Core symptoms include inattention, hyperactivity, impulsivity, and cognitive dysfunctions, causing a significant burden in multiple domains of daily life. Delayed brain maturation in childhood and adolescence is suggested as neurobiological underpinning of ADHD, but longitudinal studies are scarce and have partly revealed divergent results. The aim of the present project is to investigate the neurobiological mechanisms underlying the developmental course of ADHD within an independent, closely monitored, and well-characterized longitudinal sample (Dutch NeuroIMAGE cohort). Brain anatomical scans of initially 1,069 children (with and without ADHD) will be analysed with regard to the development of cortical thickness, surface area, and subcortical volumes, from childhood over adolescence into adulthood. An additional ultra-high field (7 Tesla) brain scan acquired in young adulthood will be used to precisely investigate cortical myeloarchitecture. All measures will be analysed with respect to clinical outcomes, that is, comparing patients with persistent ADHD, patients with ADHD in childhood who have remitted into adolescence or adulthood, and healthy controls. To further understand what mediates or moderates individual differences in ADHD-associated brain maturation, the role of genetic and environmental risk factors will be considered. This project is expected to lead to an enhanced overall picture on the developmental trajectories of ADHD. Identification of interindividual differences between individuals with persistent ADHD and those who recover as well as influencing factors will not only provide further insights into the neurobiological underpinnings of ADHD, but could also have high value for individualization and optimization of treatment approaches.

Mots clés : adhd, brain structure, development, longitudinal, intracortical myelin

Participants :
- Radboud University Medical Centre (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187624.32 €
Projet Sugarcoating matters (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

During my post-doctoral studies, I have shown that sugarcoating of proteins, “N-glycosylation” specifically, is essential for the development and a potential therapeutic target in the blood cancer myeloproliferative neoplasms. Here, I show that differential expression of three enzymes that are key to protein sugar coating are strong novel prognostic factors in the blood cancer acute myeloid leukemia (AML). Specifically, these enzymes remove or add glucose molecules of the N-glycan sugar tree. Removal of the outer glucoses is essential for retaining N-glycoproteins within the endoplasmic reticulum (ER) and unprocessed N-glycans contain a high number of mannose sugars. I hypothesize that unprocessed N-glycoproteins such as growth receptors and drug removal pumps escape the ER and are expressed on the cell surface at a higher level due to abnormal expression of genes implicated in sugar coating (ALG10B, MOGS and PRKCSH). This in turn contributes to AML development and poor outcome. To proof my hypothesis, I will decipher the role of key enzymes in N-glycan glucose addition and removal to myeloid oncogenesis (aim 1A) and drug resistance (aim 1B) using colony forming unit assays and cell lines that express ALG10B or lack MOGS/PRKCSH (CRISPR-Cas9 knockout). Additionally, I will assess mannose abundance and targetability on primary AML versus healthy control bone marrow samples (aim 2A), and map N-glycan structures using recently developed high-throughput mass spectrometry and analyses techniques (aim 2B). I will correlate structural N-glycan profiles with expression of N-glycan processing enzymes assessed through RNA-sequencing to create a full picture of N-glycosylation aberrancies in AML. This study will decipher the molecular mechanisms underlying aberrant N-glycosylation in AML and provide anchor points for novel AML therapies. This is important, because the current 5-year overall survival rate of AML is only ~30% so therapy improvements are highly warranted.

Mots clés : glycobiology

Participants :
- Radboud University Medical Centre (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187624.32 €
Projet DETECT-SV-RD (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Rare Genomic Diseases (RGDs) affect >200 million individuals globally, however less than half of patients receive a molecular diagnosis, forcing millions into year-long diagnostic odysseys, and limiting the possibilities for personalized care. New studies suggest that forms of DNA mutation affecting many base pairs of at once, so-called 'Structural Variations' (SVs) and 'Short Tandem Repeats' (STRs) may play a dominant role in the biological underpinnings of many undiagnosed RGDs. The DETECT-SV-RD project will utilise one of the largest-to-date RD-patient datasets, containing >1,400 genomes obtained by latest long-read sequencing and optical genome mapping technologies, to identify the full spectrum of SVs and better understand their impact on disease formation. To achieve this, a new computational workflow for detecting SVs will be developed, which will have a special focus on mutations that occur in the most complex, repeat-rich regions of the human genome. Using these technological advances, SVs and STRs will be identified across all patients, and carefully characterized in terms of their rarity, the properties of their breakpoints and likely biological formation mechanisms. Lastly, these insights will be combined with orthogonal 'omics' and phenotypic data to gain new insights into the underlying biology of rare diseases. In collaboration with the diagnostic department at Radboudumc, new genetic tests for SVs and STRs will finally be implemented to improve patient care. The project will, for the first time, assess the effect of SVs and STRs even in complex genomic regions comprehensively and provide an estimate for their involvement in the formation of RDs in general, as well as likely a better understanding of previously undiagnosed RDs. The project will thus contribute to improving the rate of correct RD diagnoses in the future, providing substantial emotional and physical relief to affected patients and their families.

Mots clés : genome mutation, structural variation, segmental duplications, long read sequencing, optical genome mapping

Participants :
- Radboud University Medical Centre (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187624.32 €
Projet VIMAD (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Life on earth has evolved in synchrony with the day-night cycle. Most species, from single-cell plants to humans, have a circadian system that operates as a pacemaker, modulating a multitude of biological processes across the 24h period. Given the ubiquitous involvement of the circadian system in our physiology, it is not surprising that motivation and related neural systems such as dopamine also vary across the day, but with large variation between individuals. Time-of-day is increasingly being utilised to strengthen treatment effects and facilitate behavioural change. However, we still lack fundamental mechanistic knowledge for establishing more effective and widespread therapeutic applications in mental health care as well as in daily life. Hence, there is a need to more fully understand the circadian clock of motivation and drive. The objective is, first, to predict “when” (i.e., at which time of day) drive and motivation are heightened and blunted, and second, to scrutinise the underlying cognitive and neural mechanisms. Specifically, in phase 1, I plan to conduct a large-scale field study using a mobile application to quantify fluctuations in motivation to engage in daily-life behaviours and cognitive mechanisms including incentive motivation, reinforcement-learning, and cognitive flexibility. Then, in phase 2, I will use this knowledge to probe the role of dopamine in time-of-day effects of motivation by pharmacologically modulating dopamine at different times of day in a subset of the participants from phase 1. The combination of field research and basic experimental research will provide unique and clarifying knowledge of how and why motivation fluctuates both within and between individuals. Given the significant role of motivation in the healthy and sick brain, the results will provide novel valuable insights for the society at large.

Mots clés : chronobiology psychobiology chronotype psychopharmacology dopamine motivation

Participants :
- Radboud University Medical Centre (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187624.32 €
Projet BigelInk (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Musculoskeletal conditions impact the patient’s mobility and dexterity. This greatly affects the patient’s ability to work and their overall quality of life. This burden could be lifted by tissue engineering and regenerative medicine solutions, which utilizes a combination of biomaterials and cells to restore functional tissues. Current biomaterials do not provide the strength needed for use in load-bearing applications as those seen in musculoskeletal conditions. BigelInk will develop a novel biomaterial formulation that mimics the mechanical properties of the native scaffolding of load-bearing tissues. It will do this by the design of a colloidal bigel, a two-component nanoparticle system with interpenetrating phases that is both tough and soft. The developed biomaterial will be tested for its biocompatibility according to world standards to enable further clinical trials. The biomaterial generated in this project will thereby provide a novel platform for tissue regeneration of load-bearing tissues.

Mots clés : colloidal hydrogel, regeneration, bigel

Participants :
- Radboud University Medical Centre (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203464.32 €
Projet ProINK4D (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

The ProINK4D project embarks on a transformative journey to pioneer the development of next-generation protein-engineered biomaterials for 4D bioprinting of dynamic tissue constructs. Inspired by the intrinsic versatility of intrinsically disordered protein polymers (IDPPs) with lower and upper critical solution temperature (LCST and UCST) phase behaviors, this project aims to create hybrid hydrogels by ingeniously combining protein polymers exhibiting opposite thermoresponse properties. This innovative design strategy sets the stage for the creation of preprogrammed, shape-morphing protein hydrogels, paving the way for the development of responsive protein hydrogel actuators with enhanced efficiency. With a comprehensive research plan spanning bioproduction, material characterization, bioink and bioresin optimization, and advanced 4D bioprinting, ProINK4D promises to make a significant impact on both scientific understanding and practical applications in the realms of tissue engineering and regenerative medicine. Moreover, the project emphasizes rigorous project management, research innovation, and effective science communication to ensure the highest scientific quality and societal relevance of the generated knowledge and technology.

Mots clés : protein polymers, 4d bioprinting, soft actuators, tissue engineering, bioinspired hydrogels, regenerative medicine

Participants :
- University Medical Center Utrecht (Pays-Bas) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université de Valladolid (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 181152.96 €
Projet CO2MMITMENT (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

During the CO2MMITMENT project, immobilised photosynthetic microorganisms will use CO2 in biocoated reactors to produce photosynthetic pigments. From a research point of view, four research objectives have been identified: First, the photosynthetic microorganisms will be selected based on their desiccation resistance, ensuring high survival rates within the immobilisation matrix and high levels of pigment production. Second, biodegradable copolymers will be developed as a novel immobilisation matrix. Third, the pigment production will be optimised to ensure high productivity of the biocoatings. Lastly, the process will be scaled up to use novel coated bioreactor configurations. Other objectives are the exchange of knowledge and skills between the ER and the hosts which will be ensured by adequate management and training. The results will be shared open access with the general public, scientists and industry allowing appropriate communication, dissemination and exploitation of the results. The development of these biocoated reactors will allow the ER to participate in the two-way, interdisciplinary knowledge transfer, acquiring new skills in the field of environmental biotechnologies and bioreactor engineering (from the host) and the assessment of polymers (from the secondment), while sharing her knowledge on microbiology and mass spectrometry with the host and the secondment partner. These exchanges will allow her to develop the necessary skills for a successful career in the scientific field, whether in academia or industry. The CO2MMITMENT project will allow the exchange with industrial partners, which could allow future collaborations and lead to innovation and entrepreneurship in the EU. In addition, CO2MMITMENT will commit to open access science, and strengthen the position of the EU in reducing greenhouse gas emissions by 55% by 2030, allowing the Union’s industry leadership in the field and therefore its competitiveness and growth.

Mots clés : cell immobilisation, extremophilic microorganisms, pigment production, biocoated reactors, copolymers

Participants :
- Leibniz-Gemeinschaft (Allemagne) — Partner, associated partner, Recherche, subvention : 0.0 €
- Université de Valladolid (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 209914.56 €
Projet Bmem-Malaria (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Malaria is one of the leading life-threatening diseases with a reported 627,000 deaths and 241 million infections in 2020, mostly in low-income countries. Despite the advances gained by control measures, malaria incidence by Plasmodium falciparum (Pf) has plateaued in the last decade. Intervention through vaccines and antibody therapy shows promising results, yet long-lasting protective immunity remains unattainable. Anti-malaria memory B cells comprise transcriptionally distinct sub-populations, but their contribution to protective immunity is unclear. Here, I plan to combine state-of-the-art strategies to identify the cellular and molecular features of protective immunity offered by B cells and encoded antibodies, respectively. To that end, I will use the unique samples from controlled human malaria infection trials to isolate memory B cells reactive to Pf antigens, obtain transcriptome and immunoglobulin (Ig) gene sequences at the single cell level and measure antibody inhibitory properties at the monoclonal level. Transcripts signifying resting, activated or exhausted phenotype will allow memory B cell clustering, whereas Ig gene features will help define clonal expansion and selection strength of antibodies. By cloning and testing antibodies in specialized in vitro and in vivo assays, I aim to discover potent inhibitory antibodies targeting different parasite developmental stages. I will reveal the protective antibody molecular properties defined by Ig gene features, affinity, and epitope specificity. By single-cell level integration of transcriptome and antibody functionality for the first time, this project will not only deliver potent parasite inhibitory antibodies of therapeutic potential but also lay a clear blueprint for attaining protective immunity through future vaccine designs. This fellowship will support me in acquiring interdisciplinary expertise and advancing my career as a leading scientist in B cell immunology and malaria vaccinology.

Mots clés : malaria, b cell immunology, antibodies, ig gene repertoire

Participants :
- Leiden University Medical Center (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187624.32 €
Projet MiniMI (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Cardiovascular disease remains one of the leading causes of death worldwide, with more than 4 out of 5 of these due to heart attacks. Following a myocardial infarction (MI) the loss of cardiomyocytes (CMs) is irreparable due to their non-proliferative state. Following a MI one of the most promising forms of recovery is using therapeutic drugs. Since generating a new drug requires considerable amounts of money and animal testing there is a need for alternative models such as human induced pluripotent stem cell (hPSC) models. hPSCs provide an excellent platform to model cardiac disease, although 2D models are too immature and currently 3D models are not viable for screening of therapeutic compound libraries. To solve this, I aim to implement a 'kill switch' in a subpopulation of a 3D cardiac tissue, that when triggered will induce necroptosis in the population, simulating a localized heart attack. Integrating macrophages will improve the physiological relevance and cTnT-FUCCI CMs will be used to monitor CM proliferation. To generate this innovative, dependable, inducible model of MI using hiPSCs, the project is divided into 3 achievable goals. 1. Generate a hPSC cell line with inducible kill switch system 2. Integrate macrophages into microtissues, induce the kill switch, investigate response to localized cell death and cellular changes producing a scRNA-Seq timeline 3. Incorporate cTnT-FUCCI cardiomyocytes to investigate cardiac regenerative therapies I will receive state-of-the-art genetic modification training to generate the cell line (Goal 1), immune cell generation and integration (Goal 2) and bioinformatic study to identify key pathways identified through scRNA-Seq data generated from the MiniMI model to trial cardiac regenerative compounds (Goal 3). This project will not only generate a reliable model of MI capable for screening of cardioprotective compounds, but also a malleable model suitable for easy adaptation to other researchers interests.

Mots clés : inducible disease model, heart attack in a dish, cardiac regeneration, immune cell integration and response

Participants :
- Leiden University Medical Center (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187624.32 €
Projet CollabHOME (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Collaborative housing models provide some form of collectivism and community ownership connected to the ownership and use of the housing. Initiatives aim to address problems of housing affordability and quality, as well as provide other social benefits to residents and the surrounding neighborhood through the provision of intermediate tenure between full ownership and renting. As housing pressures grow across Europe and internationally interest in this form of housing has grown. However, there is currently a lack of evidence regarding the extent to which these initiatives are able to provide affordability for residents and other social benefits in the medium to long term whilst respecting the rights of individuals. CollabHOME aims to understand how collaborative housing tenures are performing in operation, regarding these goals of housing affordability for residents of the initiative and other social benefits, and in relation to existing legal and policy frameworks. There is a growing body of research exploring the processes through which such housing projects are developed, their relationship to the state and the social relation of living within such communities. This project will contribute to this field through examining the maintenance phase of these projects and understanding the way that tenure is structured in these models. CollabHOME will conduct nine case studies of collaborative housing initiatives across three national contexts in order to model the inflection points of interaction of collaborative housing initiatives with prevailing legal, policy and social frameworks to understand how and if affordability and other benefits are maintained. It will also map housing tenure types internationally according to a model of rights and responsibilities and collateevidence of maintenance of affordability and long-term goals. Through these activities, CollabHOME will produce valuable evidence on the performance of collaborative housing over time.

Mots clés : collaborative housing, tenure, co operatives, community land trusts

Participants :
- Université Rovira i Virgili (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165312.96 €
Projet CRISPRCINIMM (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Chromosomal instability (CIN) and the resulting aneuploidies can fuel the dramatic karyotype changes characteristic of tumorigenesis, helping tumors to alter the expression of immune checkpoints and evolving phenotypes related to immune evasion or stimulation. Anti-tumor immunity appears to be dependent on the type and origin of the tumor, while immune evasion has become an obstacle to designing effective anticancer therapeutics. Understanding when CIN promotes or suppress anti-tumor immunity is therefore needed. However, the mechanism and initiators by which this adjustment occurs and the role that aneuploidy, CIN or specific karyotypes have in this transition are still in the dark. In order to understand how CIN drives tumor evolution, we need to know how CIN guide cells into different immunogenic responses. Identifying the genes that adjust the role of CIN and aneuploidy in immune evasion can therefore help us unravel the origins of malignant growth and in the future develop more appropriate therapeutic approaches. My project plan is set to find the genes that trigger and connect chromosome missegregation to the interferon-inflammatory response in cells suffering from CIN using an unbiased genome-wide CRISPR KO screen coupled to a suicide gene switch in human fibroblasts. The use of a suicide gene switch, normally used for cell-based therapy, allows separation of cells that have lost the inflammatory pathway while the screen, along with a next generation sequencing, will find the genes related to that loss. This screen will serve as a base to understand what underlies cancer immune evasion in chromosomally unstable cells.

Mots clés : cin, inflammatory response, cancer, crispr, suicide genes

Participants :
- University Medical Center Groningen (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187624.32 €