Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet Degron Miner (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The proteins of a cell are constantly turned over to adapt to changing environments or to eliminate damaged protein species. 80% of protein degradation is mediated via the ubiquitin-proteasome system (UPS). Specificity of the UPS is conveyed by E3 ubiquitin ligases (E3s), which transfer ubiquitin chains onto substrates to mark them for proteasomal degradation. E3s recognize their substrates via motifs termed degrons. Identifying degrons of all E3s would boost our understanding of proteostasis and would help designing pharmacologic strategies to modulate E3 activity. However, the “degron logic” of most of the >600 E3s encoded in the human genome remains elusive. This gap in our understanding of E3-degron relationships is related to the fact that degrons can be encoded by chemical modifications/posttranslational modifications (PTMs), which are not amenable to previously developed high-throughput degron discovery approaches via functional genomics. Here, we propose the Degron Miner platform as a high-throughput approach to systematically investigate the impact of PTMs on target protein stability. To this end, we will generate a 9000-member DegTag library consisting of modified peptides linked to a ligand that binds a nano-luciferase-tagged target protein. This library can be screened in a high-throughput fashion in live cells to select DegTags that efficiently degrade the target protein. To unravel the underlying mechanism and match E3s to the identified PTM-degron, I will employ FACS-based CRISPR/Cas9-KO screens and proteomics-based interactomics approaches. Further, I will leverage the identified PTM-degrons in chemical biology and FACS-based CRISPR/Cas9-KO screens to identify the endogenous substrates of E3s and the mechanisms leading to PTM deposition. Ultimately, the Degron Miner platform will deorphanize E3-substrate relationships and biological pathways involved in the regulation of protein degradation and will additionally provide tools to modulate E3s.

Mots clés : e3 ubiquitin ligase protacs molecular glues posttranslational modifications ptms

Participants :
- CeMM Research Center for Molecular Medicine (Autriche) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 230184.72 €
Projet HINOVA (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

One of the current main goals in particle physics is the precise determination of Higgs boson properties, which simultaneously serves as a probe to new physics beyond the Standard Model (SM). The SM has been highly successful in describing the fundamental interactions of nature. However, the nature of the Higgs boson is not completely determined, and unsolved problems such as the origin of dark matter persist. These challenges call for precise studies of Higgs boson properties and searches for new physics, which are being conducted at the Large Hadron Collider (LHC). In this context, precise comparisons between theoretical predictions and experimental measurements in collider observables are crucial, particularly in boosted Higgs boson production associated with a vector boson or jet. These comparisons require advanced multi-loop calculations for higher-order quantum corrections in perturbative Quantum Field Theory.  HINOVA will develop novel analytic techniques for multi-loop calculations, and aim to provide cutting-edge predictions for gluon-fusion Higgs boson production associated with a Z boson or jet at the LHC in the boosted region. Its primary goal is to analytically compute the missing next-to-leading order quantum electroweak corrections for these predictions. The main challenge lies in the calculation of two-loop four-point Feynman integrals involving top quarks, Higgs and gauge bosons. This challenge will be addressed using AsyInt, a novel analytic tool independently developed by the researcher. Its secondary goal is to establish a new method in AsyInt to analytically compute three-loop four-point Feynman integrals involving top quarks at high energies, which appear in next-to-next-to-leading order quantum chromodynamic (QCD) corrections for these predictions. HINOVA will deliver new results and methods that are instrumental for the most precise studies of Higgs boson properties and for new physics searches at the LHC and future high-energy colliders.

Mots clés : higgs boson physics, electroweak physics, collider physics, lhc, perturbative quantum field theory, multi loop feynman integrals, scattering amplitudes, automation and tools

Participants :
- Organisation européenne pour la recherche nucléaire (Suisse) — Coordinator, beneficiary, Recherche, subvention : 292118.88 €
Projet B-ALLeles (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

While mutations at protein-coding sequences have been extensively characterized, the functional role of disease-associated non-coding variants remains largely elusive. In fact, germline non-coding variants are often associated with increased risk of childhood cancers. In B-cell derived acute lymphoblastic leukemia (B-ALL), the most common type of cancer in children, non-coding sequence variation at lineage-specific genes, such as IKZF1, GATA3 and CEBPE is associated with disease. Interestingly, the strongest risk factor maps at ARID5B, a DNA-binding protein described to promote the removal of repressive histone marks. Still, the role of ARID5B in leukemia and haematopoiesis remains largely uncharacterized. Thus, we hypothesize that non-coding variants associated with B-ALL affect the activity of distal regulatory elements, modulating the expression of ARID5B and other B-cell lineage-specific genes (objective 1). We further postulate that ARID5B promotes the de-repression of lineage-specific genes (objective 2), playing a crucial role in B-cell development and B-ALL initiation and progression (objective 3). To test these hypotheses, I will develop a novel CRISPR screen approach to dissect ARID5B enhancers at single nucleotide resolution (work package 1). I will use a combination of genomics and transcriptomics methods after acute and prolonged degradation of ARID5B to elucidate the molecular function of ARID5B in B-ALL (work package 2). Finally, I will use mouse models and focus on the physiological relevance of ARID5B in B-cell development and leukemia initiation and progression, in vivo. (work package 3). Together, I will dissect the role of non-coding variants at leukemia-associated loci, characterize the molecular function of ARID5B and elucidate the pathophysiological relevance of ARID5B.

Mots clés : non coding variants, epigenetics, crispr screens, hematopoiesis, leukemia, enhancers, gwas

Participants :
- St. anna kinderkrebsforschung gmbh (Autriche) — Coordinator, beneficiary, Recherche, subvention : 183600.96 €
- CeMM Research Center for Molecular Medicine (Autriche) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €
Projet AxionCount (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

AxionCount aims to explore the theoretical and phenomenological implications of the existence of multiple axions in nature. Axions are hypothetical particles that could resolve two major enigmas in fundamental physics: the origin of dark matter and the absence of CP violation in the strong sector. Given their potential significance, extensive theoretical efforts and strong experimental programs have been launched to investigate their existence. However, several well-motivated theories suggest that the axion may not exist in isolation but alongside other scalar companions. Despite this, much current research focuses on the single axion paradigm. AxionCount's primary goal is to explore how the axion experimental program could address the questions: How many axions exist? How would the presence of multiple species alter the axion quest? The project will develop new tools to study the implications of multiple axions. On the theoretical side, AxionCount will investigate axion oscillations, construct the Effective Field Theory for multiple axions, and explore models that predict the existence of several axions. On the phenomenological side, the project will assess how experimental constraints are modified by the presence of multiple axions. Special emphasis will be placed on how experiments such as CAST and IAXO at CERN, the host institution, can distinguish a multiple axion signal from that of a single axion. Finally, from a cosmological perspective, AxionCount will analyze the evolution of multiple axions in the early universe and calculate the axionic dark matter abundance. Overall, AxionCount aims to rethink the parameter space of multiple axions, expanding experimental opportunities and fostering synergies not only between theory and experiment, but also among different experimental efforts, as their findings may be interconnected within the multiple axion framework.

Mots clés : axions, axion like particles alps, particle phenomenology, particle cosmology, dark matter production mechanisms, strong cp problem, multiple axions, effective field theory eft , hilbert series

Participants :
- Organisation européenne pour la recherche nucléaire (Suisse) — Coordinator, beneficiary, Recherche, subvention : 292118.88 €
Projet TopJAm (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

The Large Hadron Collider (LHC) at CERN allows us to investigate the fundamental laws of nature at unprecedentedly high energy. Our capability to harness this stunning potential relies on our ability to compute theoretical predictions to be compared against the experimental measurements. Keeping the theoretical uncertainties in line with the experimental ones requires computing theoretical predictions at least at the next-to-next-to-leading order (NNLO) in Quantum Chromodynamics (QCD), the quantum field theory which describes the strong interactions. A fundamental ingredient entering the theoretical predictions are the scattering amplitudes, which encode the probability distribution of the scattering processes observed in the experiments. The project targets the computation of the two-loop amplitudes for the production of a top-quark pair in association with a jet. These amplitudes are the main bottleneck towards obtaining NNLO predictions for this process, which is a high priority of the LHC physics programme. The presence of the top-quark mass in a process involving so many particles represents a substantial step up in complexity with respect to the state of the art. The main difficulty lies in the appearance of classes of special functions whose systematic treatment and efficient evaluation are still open problems. Overcoming this bottleneck will require a close interplay between physics and mathematics. The algebraic complexity of the amplitudes themselves also represents a formidable challenge. I will tackle it by employing cutting-edge techniques based on numerical sampling over finite fields and advanced algorithms of rational reconstruction based on algebraic geometry and physical properties. The success of the project will not only open the door to NNLO predictions for this important process, but will improve significantly our capability of computing high-precision predictions for high-multiplicity processes in general.

Mots clés : scattering amplitudes, qcd, perturbative qcd, lhc, collider physics

Participants :
- Organisation européenne pour la recherche nucléaire (Suisse) — Coordinator, beneficiary, Recherche, subvention : 210789.12 €
Projet POTRET (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Polycystic ovary syndrome (PCOS) affects 11-13% of reproductive-age women and is one of the leading causes of anovulatory infertility. Women with PCOS have elevated androgen levels, polycystic ovarian morphology, and ovarian dysfunction. The PCOS endometrium is exposed to constant estrogen, which leads to progesterone resistance and impaired decidualization. As a result, PCOS women are twice as likely to have a non-receptive endometrium. This hinders embryo implantation and increases the risk of pregnancy complications, such as miscarriage. However, whether changes in the cellular complexity and heterogeneity of the endometrium during the menstrual cycle contribute to PCOS-specific endometrial dysfunction remains unclear. The overarching aim of this MSCA-PF project is to uncover PCOS and cell type-specific endometrial dysfunction across the menstrual cycle at the single cell level and to test whether the identified markers can serve as targets for future drug development. Using a unique collection of human endometrial biopsies from women with and without PCOS and single nuclei RNA sequencing, I will (1) map the endometrium at the single-cell level at four different menstrual stages, define the composition of cell types and key molecular regulatory networks; (2) establish and characterize 3D mono- and co-culture models of patients endometrium and investigate their ability to mimic tissue of origin; and (3) determine factors that facilitate PCOS-specific epithelial-stroma communication and endometrial response to novel drug treatments. By accomplishing these goals and sharing the transcriptomic data as a PCOS endometrial cell atlas and protocols for patient-derived cell models, the proposed project will provide valuable resources for new discoveries. Ultimately, the project aims to improve the diagnosis, treatment, and prevention of endometrial dysfunction in PCOS. Further, it provides me with a strong training path towards academic independence in Europe.

Mots clés : polycystic ovary syndrome, endometrium, single nuclei rna sequencing, three dimensional endometrial epithelial organoids, microfluidics

Participants :
- Institut Karolinska (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 236340.0 €
Projet HiCoLat (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Lattice Quantum Chromodynamics (LQCD) is the only known ab-initio approach to compute observables in the non-perturbative regime of the strong interactions of particles and fields. The theory of strong interactions is solved numerically in finite volumes on an Euclidean space-time grid. The framework of LQCD has systematically improvable statistic and systematic uncertainties. It provides highly relevant theoretical input for high-energy and nuclear physics. The precision of LQCD computations has significantly improved in the last years thanks to algorithmic advancements. This project aims to further improve the precision of phenomenologically important observables. The improvement will be achieved by the development and application of noise reduction techniques to reduce statistical uncertainties at computationally challenging, very fine resolutions of LQCD simulations. The focus of this project will be on the improved determination of the hadronic vacuum polarization contribution to the anomalous magnetic moment of the muon. Precise theoretical predictions of this observable are of utmost importance in the search for physics beyond the Standard Model of particles as the uncertainties of the experimental results will significantly decrease in the upcoming years. The computation of the hadronic vacuum polarization in the framework of LQCD suffers from an exponentially enhanced increase of the noise-to-signal ratio in the low energy region. Furthermore, the precision of state-of-the-art determinations is bounded by systematic uncertainties due to the presence of the finite grid. Both uncertainties will be addressed and reduced in this work. Furthermore, the approach will be tested in the computation of B-physics observables that are needed to investigate currently observed anomalies in the heavy quark flavor sector of the Standard Model.

Mots clés : lattice qcd, muon, supercomputers, lepton, bottom quark, quantum field theory, scientific computing

Participants :
- Organisation européenne pour la recherche nucléaire (Suisse) — Coordinator, beneficiary, Recherche, subvention : 210789.12 €
Projet CLIMWELB (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Economic Sciences
Statut du projet : SIGNED

Subjective well-being (SWB) is gaining recognition as a key indicator of societal progress, yet it is often overlooked in assessments of the impacts of climate shocks, which are increasing in both severity and frequency. This research, CLIMWELB, aims to fill this gap by pursuing three specific research objectives: 1) examining the impact of climate shocks—drought, flooding, and extreme temperatures—on SWB, 2) investigating the mechanisms through which these shocks affect SWB, and 3) exploring the role of subnational foreign aid in mitigating the potential adverse effects of climate shocks on SWB. CLIMWELB will focus on Small Island Developing States (SIDS), which rank among the most vulnerable globally to climate shocks and receive disproportionately higher levels of foreign aid relative to their economies. To achieve the specific research objectives, CLIMWELB will employ quasi-experimental methods, machine learning techniques, and a suite of robustness checks. Geocoded data on climate shocks and subnational foreign aid will be extracted from the European Centre for Medium-Range Weather Forecasts (ECMWF) and AidData project databases, respectively, while geocoded household data will be drawn from the Demographic and Health Surveys (DHS), the World Bank Microdata Library, and the Afrobarometer database. CLIMWELB will shape scientific discourse by providing the first evidence of the impact of climate shocks on SWB in vulnerable contexts such as SIDS, and offer pioneering insights into the role of subnational aid as a mitigating factor. In addition, CLIMWELB's findings will interest various stakeholders—including SIDS governments, foreign aid donors, international organizations (UN and EU agencies), NGOs, and international financial institutions (World Bank)—and inform their policies aimed at safeguarding small island communities and other vulnerable contexts.

Mots clés : climate shocks, drought, flood, extreme temperature, subjective wellbeing, happiness, life satisfaction, subnational foreign aid, difference in differences, small island developing states

Participants :
- Université de Malte (Malte) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 256642.8 €
- The malta foundation for the wellbeing of society (Malte) — Partner, associated partner, Autres, subvention : 0.0 €
- Fonds International de Développement Agricole (Italie) — Partner, associated partner, Organismes publics (hors enseignement & recherche), subvention : 0.0 €
Projet AdaM (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Higher brain functions, such as decision-making, are associated with the coordinated activity of multiple cellular structures (e.g., cell bodies and cellular processes of neuronal and non neuronal cells) distributed over multiple brain areas. Recent technical developments enable monitoring this ensemble activity across different brain regions with high (i.e., cellular and subcellular) resolution using large field-of-view (FOV) two-photon (2P) mesoscopy. However, optical aberrations mostly due to light scattering strongly limit the application of these technologies when the imaging depth within the brain increases. To address this limitation, I will here design, develop, and validate the first adaptive optics (AO) mesoscope, combining the strength of adaptive aberration correction with the power of large FOV 2P mesoscopy. I will first benchmark this novel approach to image ensemble Ca2+ dynamics of small brain structures (e.g., processes of neuronal and non-neuronal cells) in living mice over large FOV and at increasing imaging depths. I will then focus on recording Ca2+ signals from processes of astrocytes, the main non-neuronal cell type in the brain, which play fundamental roles in brain physiology. I will study how networks of thin astrocytic structures encode behavioural information over multiple cortical regions during a decision- making task. Finally, I will apply analytical methods based on information theory and machine learning to extract emergent properties of distributed ensembles and their correlation with behaviour. In conclusion, I will combine expertise in optical engineering, neuroscience, and computation to reveal the functional dynamics of the fine cellular structures across multiple cortical areas. This project will allow extracting details about ensemble dynamics that have long remained inaccessible, contributing to elucidate the contribution of coordinated activity of cellular and subcellular structures to higher brain function and behaviour.

Mots clés : adaptive optics, two photon random access microscopy, calcium imaging, sub cellular resolution, astrocytes, l5 neurons, somatosensory cortex, motor cortex, information theory, machine learning

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 172750.08 €
- Universitätsklinikum Hamburg-Eppendorf (Allemagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet RECLEAN (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

RECLEAN aims to study the impact of human activities on the environment of Hellenistic, Roman and Byzantine Egypt (ca. III c. BCE - VII c. CE), the effects of climate variability and pollution on the health of the inhabitants of Egypt, and the people’s degree of awareness of environmental issues and their consequences on health. Research will focus on a body of sources that have not yet been comprehensively analysed, the papyri from Egypt written in Greek and Latin, which will be integrated with literary and historical sources, archaeological finds and inscriptions, and with the results of studies based on palaeoclimate proxies and palaeopathological samples. The outgoing phase of RECLEAN (years 1 and 2) will take place at the Departement Altertumswissenschaften of the University of Basel, which hosts the Basel Climate Change and Ancient History Lab, an interdisciplinary initiative dedicated to the study of ancient environmental issues: here the fellow will receive specific training in Environmental History of Antiquity, essential for the pursuit of the project’s objectives, in a vibrant and multidisciplinary environment that brings together specialists in the Humanities and in the Environmental Sciences. The return phase (year 3) will take place at the Dipartimento di studi umanistici e del patrimonio culturale of the University of Udine, where the fellow will consolidate her preparation in Papyrology and further delve into the subject of “environmental awareness” in Antiquity. The results of RECLEAN will be made available to the scientific community through open access publications and presentations at conferences, while the communication activities will reach a wider audience with the aim of stimulating a reflection and debate on environmental issues in a historical perspective, thus contributing to raising awareness of the magnitude that environmental problems have reached today when compared to the past and the need for urgent intervention.


Participants :
- Université d'Udine (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 320924.16 €
- Université de Bâle (Suisse) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €