Wild bees provide essential ecosystem services by pollinating the majority of flowering plants. Moreover, society is becoming increasingly dependent on bees as demand for pollinator-dependent crops expands globally. However, many bee populations are declining around the world, in large part due to interaction between multiple environmental stressors including pathogen spread, air pollution and climatic changes. All these stressors are likely to impact the physiology of wild bees. Especially, they can affect their oxidative status by increasing the production of reactive oxygen species. Bee endogenous antioxidant system may then be overwhelmed, which can lead to oxidative stress and give rise to structural and functional damage, potentially causing death. However, the ingestion of exogenous dietary antioxidants should allow for recovering an optimal antioxidants/pro-oxidants balance and then attenuate the damaging effects of stressors (self-medication). Regulation of oxidative stress using dietary antioxidants could therefore be one of the key mechanisms determining the capacity of organisms to cope with living in a changing world. As such, there is a clear need to understand how pollen antioxidants could contribute to the resilience of bees to global changes. The proposed research aims to demonstrate whether conditions for self-medication to counter oxidative stress occur in wild bees to face global changes. The project will rely on innovative methods in ecology, analytical chemistry, metagenomics, proteomics and microbiology. This approach translates the multidisciplinarity and the comprehensiveness of my research activities. The expected results could greatly improve pollinator conservation programs by proposing nature-based solutions, such as promoting a medicative flora.

The Large Hadron Collider (LHC) at CERN has opened a new era in the exploration of the fundamental laws of Nature. It will be the world’s energy frontier machine for the foreseeable future, and the question of what lies beyond the Standard Model (SM) of particle physics is the primary target of its physics program. Effective field theories (EFTs) provide a unified, model-independent framework to address this question, that can make use of measurements from the full spectrum of LHC physics and beyond. This project aims to develop EFT measurements within ATLAS and with the wider particle physics community, including the widest possible spectrum of measurements in LHC Run 3 data. These will include in particular ATLAS measurements involving Higgs bosons, top quarks, pairs of W and Z bosons and the Drell-Yan process. The results of measurements outside ATLAS will also be included to achieve the strongest possible constraints. The project will focus on improving the EFT sensitivity of these analyses, establishing their EFT interpretations, and performing wide combinations of results (both within and outside ATLAS) to obtain the strongest possible constraints on EFT parameters. Combinations outside the scope of ATLAS alone will require the ability to efficiently exchange information within the wider particle physics community, in particular on statistical models. The development of methods, standards and tools toward this goal, following FAIR principles, will constitute a key part of the project. The consortium involves teams from the LAPP (Annecy), IJCLab (Orsay), LPC (Clermont-Ferrand) and LPSC (Grenoble) laboratories of IN2P3, as well as external partners from the universities of Valencia (Spain), Heidelberg (Germany), New York (United States) and CERN (Switzerland). Its members provide strong expertise in ATLAS measurements with EFT sensitivity, the reinterpretation of LHC analysis results, the theory framework of EFT measurements and global fits of EFT results.

Cytoskeleton remodelling is a dynamic process involved in most physiological and pathological events. Many drugs target microtubule turnover, but are often associated with side effects and resistance. In this project, we want to target actin filament turnover, which regulates cell shape, motility, migration, division. So far, most drugs targeting actin cytoskeleton remodelling act upstream of this signalling pathway, and very few have reached the market. Here, we will target cofilin, an actin-depolymerizing factor, which stands downstream of the pathway. LIM kinases (LIMKs) are the main regulators of cofilin: they phosphorylate it leading to its inactivation. LIMKs are misregulated in many pathologies. Many small molecules inhibiting the kinase activity of LIMKs have been developed to prevent their action on cofilin. However, only one has reached the clinical stage, with no published results. Actually, achieving selective inhibition of specific protein kinases is challenging, and off-target interactions frequently occur with unrelated kinases. Moreover, a small molecule that targets the active site of a given kinase does inhibit the phosphorylation of all its potential substrates. That is why, we want to inhibit cofilin phosphorylation by a completely different approach based on a new paradigm: disruption of the protein-protein interaction between LIMKs and cofilin, in order to develop highly selective and specific inhibitors. This approach is motivated by the very atypical LIMKs/cofilin interaction, exclusively due to the binding of an alpha-helix of cofilin with a groove of LIMKs. We will disrupt this interaction by using a promising class of therapeutic molecules, “stapled peptides”: short cyclic peptides adopting an alpha-helical conformation and exhibiting cell penetration abilities and favourable pharmacokinetic properties. Our project will bring valuable contribution to develop chemical biology tools with a direct drug discovery perspective.

Biomass is the largest source of renewable carbon, so there is a rapidly growing interest on its use for production of decarbonized organic compounds, from fuels to specific. Transformation of biomass derivates to valuable products by electrocatalytic methods is a promising technology. However, the technology is still in its relative infancy, and challenges to be tackled span from laboratory development to the necessary scale-up towards industrial use. In particular, understanding processes and study of reaction intermediates requires new efficient in-operando tools. The MEGOPE project wants to deal with those great challenges by setting a new methodology to investigate rapidly and in-operando electrochemical valorisation of complex mixtures. It will give access to a better understanding of the underlying processes involved in molecular electro-reactivity and go a step further into scaling-up to industrial needs. Thus, two kind of instrumentation will be developed: a DEMS coupled to a Chemical Ionization Mass Spectrometer for organic volatile detection, and an innovative new soft ionization source (V-EASI) associated to a MS/MS for rapid identification of intermediates and high mass products, whose development is the core of the project. This methodology will be used first on already studied compounds issued from cellulose transformation (HMF, furfural) and in a second step to less known phenolic compounds issued from lignin decomposition. The final aim of the project is to use the developed methodology to investigate a step further in more complex mixtures, notably fractions issued from lignin valorisation. The MEGOPE project associates two complementary laboratories: ICP (Univ Paris Saclay) whose team is well known for their MS development and IRCELYON (Univ Lyon 1) experts in electrocatalysis and biomass valorisation, in order to bring state of the art instrumentation development to biomass transformation identification.

The prevalence of Western diet-induced metabolic syndrome is booming contributing to persist increase of cardiovascular diseases (CVD), including atherosclerosis. Many patients with obesity suffer from adverse metabolic complications and associated atherosclerosis, whereas other remain metabolically healthy. Thus, understanding the pathogenesis of these associated diseases and identifying new therapeutic targets is of utmost importance. The aim of the present research is to characterize tryptophan and phenylalanine gut-dependent metabolites playing important roles in atherosclerosis by using “metabolomics” approaches. To this end, a combination of NRM (profiling) and Mass (targeted) metabolomics approaches will be used on mouse models of atherosclerosis and on human samples from general population. This strategy will allow us to identify and validate metabolites that can be considered as a basis for the development of new treatments of western life style-associated diseases.