Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet TuniPeps (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The spread of antimicrobial resistance among human pathogenic bacteria and fungi is a major global and European concern, urgently necessitating the development of novel antibiotics. Another unsolved global healthcare problem is the burden of infections acquired through invasive medical devices. Antimicrobial peptides (AMPs) could be the solution to both problems, but they are currently limited by high cost, insufficient efficacy and stability as well as restricted chemical options for biotechnological production. However, in a group of marine animals: tunicates, there is a major, poorly characterized superfamily of AMPs with many advantageous natural chemical modifications. These unusual post-translational modifications (tryptophan bromination, arginine/lysine mono- and dihydroxylation, tyrosine hydroxylation, C-terminal amidation/oxidation) are predicted to improve potency and stability of the mature AMPs and might enable their efficient immobilization onto various surfaces. The latter property could also prove useful for surface coatings. In the current project, we aim to explore these promising bioproducts, from predictions by bioinformatics, through isolation of animal tissues, extraction and enrichment of the actual peptides, to their chemical analysis by mass spectrometry and testing of antimicrobial potency and safety. Project TuniPeps gives a major opportunity to both the applicant and host, to combine their complementary knowledge and skills in order to identify useful natural products from marine animals, acting as blueprints for future antimicrobials. These diverse molecules and their biosynthetic apparatus might also unlock cheap biotechnological production of novel molecules in the near future.

Mots clés : natural product discovery, antimicrobials, post translational modifications

Participants :
- Université de Padoue (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 188590.08 €
Projet ConNEqtions (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Equilibrium statistical mechanics has provided a suitable setting to explain the thermodynamic behavior of macroscopic physical systems. Instead, much less is known about systems out of equilibrium that contribute to the vast majority of phenomena people experience everyday. In this project, "Constraints on Non-Equilibrium fluctuations" (ConNEqtions), we aim at deriving new and rigorous analytical results on the statistics of fluctuating observables in non-equilibrium processes. In particular, the emphasis will be on the thorough analysis of classical and quantum periodically driven systems, that constitute a timely and active topic of research. The first objective of the project is the generalization to periodically-driven Markov processes of the symmetry-induced fluctuation relations studied by the Researcher and his collaborators. The second objective is the generalization to the quantum domain of important results about level 2.5 large deviations, already established for classical time-periodic Markov chains. This in turn will lead to the derivation of new thermodynamic uncertainty relations in quantum systems with periodic driving. The project is built as an interdisciplinary effort, combining the physical background of the Researcher with the mathematical expertise of the Supervisor.

Mots clés : fluctuation relations, thermodynamic uncertainty relations, stochastic processes, periodic driving

Participants :
- Université Côte d'Azur (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195914.88 €
Projet AbVarFq (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : SIGNED

Some of the most extensively studied objects at the intersection of number theory and algebraic geometry are abelian varieties, which are projective varieties whose points form a group. The main objective of the project is to concretely represent abelian varieties defined over a finite field and classify them up to isomorphism, together with their polarizations.  The main goal has been achieved in previous years by work of the Researcher, Supervisor and collaborators in several cases, which enjoy two properties: the varieties admit canonical liftings and the p-divisible groups do not play a special role in the classification. The project deals with the cases where these crucial properties do not hold, making them theoretically more complicated to grasp, but also more interesting.  Achieving the objective will have several consequences. Firstly, we will obtain an efficient way to represent abelian varieties over finite fields, overcoming the facts that equations are too cumbersome, already in dimension 2, and that Jacobian varieties give a complete description only in low dimension and with certain kind of polarizations. Secondly, we will fill some important gaps in our current understanding of many invariants attached to the abelian varieties, like the p-rank or the Newton polygon. Third, the project will pave the way to: compute the cohomology of moduli spaces of the abelian varieties by interpolating our point-counts over finite fields; shed light one the set of conjectures connecting automorphic forms and representation theory usually known as the Langlands program; study isogeny graphs of abelian varieties over finite fields, which have the potential of being useful in (post-quantum-)cryptography; understand properties of algebraic-geometric codes via Jacobians. Note that the last two applications could have significant impact on making digital communications more secure and reliable, and hence considerably affect our society and economy.

Mots clés : abelian varieties, finite fields, polarizations, orders in finite products of number fields

Participants :
- Université Côte d'Azur (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195914.88 €
Projet RRR-XAI (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Deep Deep Learning (DL) is a form of machine learning (ML) that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts. This hierarchy allows a DL model to learn complicated concepts by building them out of simpler ones. A graph of these hierarchies would be many layers deep, and thus its name. A Deep neural network (DNN) is based on an artificial neural network model, and its core strength is that there is no need for human assistance to formally specify all the knowledge that the model needs. This makes DNNs represent the state of the art in Artificial Intelligence (AI). Despite their top performance and ubiquity of applications (from Healthcare to autonomous cars), DNNs suffer serious shortcomings. First, DNNs are considered black box models, i.e., with complex and opaque algorithms, hard to interpret and diagnose. Second, they suffer from bias, and the testing protocols for automatic recognition are not fair, as they learn patterns in the data that are not correlated to the output; e.g. they may focus on areas outside the lung in X ray images to predict the presence of COVID-19. Although DNNs outperform many other methods, they often are not right for the right reasons (RRR). RRR-XAI tackles this mismatch and bridges this gap through a tight integration of DL and symbolic AI, with the principal objective of making DL explainable. To achieve this I will follow the rationale behind XAI under the RRR philosophy and perform analyses to understand two types of phenomena that cause trouble in DNNs. Second, I will use: 1) Domain knowledge expertise as supporting evidence to explain a particular model output; 2) Neural-Symbolic computation to communicate the explanation of such phenomena in natural language. I will study two practical use cases where supporting explanations of the model output are critical: a) COVID-19 prediction from chest X-Ray images, and b) Weapon detection in alarm systems and crowds from images.

Mots clés : explainable artificial intelligence, responsible ai, deep learning, knowledge representation, neural symbolic learning and reasoning, big data, information fusion, computational intelligence

Participants :
- Université de Grenade (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165312.96 €
- Université de Sienne (Italie) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet NEUROINFLAM-MS (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Alzheimer’s (AD) and Parkinson’s disease (PD) are prevalent neurodegenerative diseases, but their underlying mechanisms remain poorly understood. Emerging evidence suggests that neuroinflammation, characterized by the release of pro-inflammatory cytokines like IL-1β, TNF-α, and INF-γ, plays a pivotal role in these diseases, challenging the conventional focus on protein aggregates (Aβ, αSyn). In AD, it has been shown that elevated IL-1β levels induce the translocation of NEDD8 from the nucleus to the cytoplasm, where it co-localizes with the E3-ligase Parkin. Together with the kinase PINK1, Parkin is crucial for the removal of defective mitochondria, with loss-of-function mutations in these genes being the primary cause of early-onset PD. Intriguingly, phosphorylated NEDD8 can activate Parkin, implicating a more complex interconnection between neuroinflammation, NEDD8-and Parkin-regulated phosphorylation-dependent signaling in brain cells. Yet, a mechanistic understanding of cellular processes triggered by neuroinflammation remain elusive. This proposal aims to investigate spatiotemporal (phospho-)proteome changes in response to neuroinflammatory stress elicited by pro-inflammatory cytokines and αSyn fibrils. To achieve this, I will combine spatial-proteomics using subcellular fractionation and hybrid-DIA in combination with the cutting-edge Orbitrap Astral mass spectrometer. Initial analyses of neuronal cell line models will be extended in a second step to hPSC derived neurons, astrocytes, microglia, and co-cultures thereof. This enhances the translational relevance by mimicking neuroinflammation in the complex tissue architecture of the brain. Finally, bioinformatically shortlisted neuroinflammation-regulated proteins and phospho-sites will be validated in cell-based models. With this project, I aspire to unravel the cellular mechanisms underlying neuroinflammation, potentially unlocking new avenues for therapeutic strategies against neurodegenerative diseases.

Mots clés : phospho proteomics, nedd8, neuroinflammation, spatial proteomics, hybriddia ms, cellular signaling, kinase signaling, hpscs, co cultured brain cells, il 1 , tnf , inf ,  synuclein

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 230774.4 €
Projet TUNEWET (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Tropical wetlands dominate wetland methane emissions globally and play a vital role in recent surges of atmospheric methane. Despite the importance of tropical wetland methane emissions in global methane budgets and future climate change, current knowledge about their magnitude, distribution and variations remains highly uncertain, which impedes effective climate strategies and actions. Through a synergy of biogeochemical (“bottom-up”) and atmospheric (“top-down”) methodologies, I propose the project TUNEWET (Towards observation-constrained UNderstanding and prEdicting of tropical Wetland mEThane emissions) to constrain tropical wetland methane emissions and their responses to climate change by integrating multiple data streams and modelling tools. I will carry out this research with Prof. Guy Schurgers at the newly founded Global Wetland Center (GWC), University of Copenhagen (UCPH). This project will gain new insights into the key processes regulating tropical wetland methane emissions and help resolve the largest uncertainty source in the global methane budget, thereby supporting science-based climate mitigation strategies.

Mots clés : tropical wetland, methane emissions, climate change, flux upscaling, atmospheric methane inversion

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 230774.4 €
Projet HLCSSLA (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : SIGNED

The goal of this project is to produce new computations of the mod p homology of labelled configuration spaces of a general manifold with labels in an arbitray spectrum. These computations have remained outstanding challenges for decades except in special cases. Recently developed techniques in stable homotopy theory, including spectral Lie algebras and synthetic homotopy theory, have proven to be useful in understanding the algebraic structure on the homology groups of labelled configuration spaces in universal cases, but are less attuned to the topology of the input manifolds. In this project, I plan to attack the problem by incorporating the homotopy-theoretic methods with approaches that take into account the geometry of labelled configuration spaces. New computations of these objects will have applications in a range of fields including stable homotopy theory, string topology, embedding calculus of manifolds, mathematical physics, and motion planning. The supervisor will be Prof. Nathalie Wahl at the department of Mathematics of the University of Copenhagen.

Mots clés : configuration spaces, homology, spectral lie algebra, spectral sequence, synthetic homotopy theory, homological stability, mapping class group

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214934.4 €
Projet NuKleOrigin (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

The Solar System has long been thought to represent the only habitable planetary system. The discovery that planets orbiting Sun-like stars are common in our Galaxy has fostered the concept of planetary habitability, which defines the conditions at the surface of a planet required for life to develop, including the presence of volatiles, energy, and organic chemistry. Elucidating the relationship between the formation pathways of rocky planets and their potential habitability is crucial in that regard. One way to approach this is to determine the origin and composition of the building blocks of planets. Meteorites are witnesses of the earliest stages of planetary accretion and are ideal for this task. Nucleosynthetic anomalies (which are mass-independent variations of the isotope composition) measured in meteorites provide insights into the building blocks of planets. They are robust tracers because they are not affected by geodynamic and chemical differentiation of the planets. However, the determination of the building blocks of planets necessitates to consider a holistic approach considering constraints from elements with different volatility and cosmochemical behaviour in all extra-terrestrial materials. For instance, nucleosynthetic anomalies of refractory lithophile and siderophile elements do not provide precise constraints on the origin of volatile elements in planets. The very recent identification of nucleosynthetic anomalies in moderately volatile elements K and Zn opens new avenues of research as robust proxies of more volatile elements. This project aims at determining the source of the nucleosynthetic anomalies of moderately volatile elements and defining the building blocks of Earth and Mars building blocks and the source of volatile elements. I will use next generation instrumentation combined with emerging technologies to carry out this project.

Mots clés : cosmochemistry, meteorites, nucleosynthetic anomalies, planet accretion

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214934.4 €
Projet GWtheory (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Since the discovery of Gravitational Waves from a binary black hole merger in 2016, we have entered a new era in exploring the Universe. Binary black hole and neutron star mergers are the primary sources of gravitational waves. High-accuracy theoretical predictions for the motion of compact binary systems play a fundamental role in interpreting data and maximizing discovery potential for present and future observations, such as LIGO-Virgo-Kagra. I have played a pioneering role in the development of a new framework aiming at efficiently calculating gravitational-wave observables using modern theoretical tools initially invented for CERN’s LHC experiments. Using this framework, we have obtained the most precise theoretical predictions for the gravitational dynamics of binary inspirals to date.  This project aims to push the precision frontier for theoretical predictions for the gravitational observables of inspiralling binary systems. This will be achieved by innovating computational methods for classical gravitational dynamics using cutting-edge techniques from quantum field theory and modern mathematics, including Feynman integrals, effective field theory, special functions and applied algebraic geometry. We will derive a set of new precision corrections for the dynamics of inspiralling binaries, including spin and finite-size effects, beyond the current state of the art. These new results will be used to construct more accurate waveform models. The latter are crucial to understanding long-standing questions in fundamental physics and astronomy with next-generation gravitational-wave observations, such as the LISA and the Einstein Telescope in Europe, which in turn may provide fundamental insights into Einstein's theory of gravity.

Mots clés : feynman loop integrals, effective field theory, post newtonian post minkowskian theory, gravitational two body problem, gravitational waves

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214934.4 €
Projet OraPickering (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Therapeutic peptides (TPs) are one of the fastest growing classes of therapeutics with clinical applications in severe and/or chronic diseases like cancer therapy, hormonal or immune disorders, and infectious or metabolic diseases. To date, most TPs can only be administered by invasive injection, which greatly influences treatment costs as well as patient compliance and wellbeing, as e.g. diabetic patients rely on regular insulin injections. Oral delivery of TPs poses a convenient alternative to circumvent these problems, but it is highly challenged by I) the harsh gastric environment detrimental to TPs and II) the poor permeability of the intestinal epithelium to TPs. To tackle these problems, I propose a novel oral delivery system for TPs based on a unique gastric stable Pickering double emulsion, which is able to I) protect TPs from degradation in the gastric environment and II) co-deliver hydrophilic TPs and hydrophobic permeation enhancers (PEs) to the absorption site; the intestinal epithelium surface. Simultaneous co-delivery of TPs and PEs is crucial, but not often achieved. As key deliverables, OraPickering will establish Pickering double emulsions for the encapsulation of hydrophilic TPs and hydrophobic PEs, explore their stability under gastric conditions, and confirm their efficacy and safety for intestinal TP delivery in vitro and in vivo. To implement OraPickering I will join forces with Prof. Nielsen from UCPH, combining my background in material and interface sciences with her expertise in TP delivery and intestinal permeation models and mechanisms. I consider this the ideal environment for my further career development, to learn relevant techniques for drug delivery and gain further experiences to emerge as an independent group leader. In summary, OraPickering provides a novel avenue for oral TP delivery, and thereby contributes to a more facile, safe, and cost-effective administration of TPs in the future.

Mots clés : drug delivery systems, oral delivery, emulsions, therapeutic peptides, intestinal absorption

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214934.4 €
Projet MIEXIA (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Cancer cachexia (CC) affects 50-80% of patients with cancer and is characterized by accelerated loss of muscle mass, which is directly linked to reduced quality of life, treatment toxicity, and lower survival. With no pharmacological treatment options, key to improving life expectancy is to understand the molecular determinants of CC, however, these are poorly defined. Mitochondrial dysfunction and inflammation can cause muscle atrophy and are considered as emerging hallmarks of CC. Exercise is the most potent approach to improve mitochondrial and muscle function, and to reduce inflammation, yet, implementing it in CC is challenging because of fatigue and pain of patients with cancer. Elucidating the molecular underpinnings of exercise’s beneficial effects represents a major scientific challenge and an untapped opportunity for medical exploitation. In this regard, unpublished data from my host lab show that muscle protein levels of the mitochondrial (mt) RNA stabilizer LRPPRC (Leucine-rich PPR motif-containing protein) are induced upon exercise and reduced in cachectic muscles. Thus, mtRNA metabolism could be a new target for CC. mtRNA metabolism is key to maintain levels of mtDNA-encoded proteins to promote mitochondrial function. Yet LRPPRC´s role in muscle mitochondrial function and CC is unexplored. I hypothesize that reduced LRPPRC is key in CC-associated muscle mitochondrial dysfunction and inflammation. Stimulation of LRPPRC could promote exercise-like benefits, establishing a new pharmacological target for CC. I aim to determine the molecular link between mitochondrial dysfunction, inflammation, and muscle atrophy in preclinical CC models and patients with CC. I will unravel the molecular pathways involved in LRRPRC’s exercise-induced effects and I will appraise LRPPRC’s therapeutic potential in CC. Results have the potential to provide crucial insights on the molecular events underlying CC and likely identify new pharmacological strategies to tackle it.

Mots clés : mitochondria, inflammation, exercise, mtrna metabolism, cancer cachexia

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 230774.4 €