Copper element is at the same time an essential micronutrient in living systems, being a cofactor of enzymes involved in many biological processes, but toxic for the cell when in excess. The understanding of mechanisms involved in intracellular copper balance between requirement and toxicity is thus crucial from fundamental and applicative points of view. Among amino acids, methionine (Met) residues readily bind copper, and interestingly many proteins involved in copper homeostasis are rich in Met. As a model case, Escherichia coli CueO multi-copper oxidase, a periplasmic protein early recognised to be involved in copper resistance in vivo, presents a Met-rich domain proposed to be involved in the oxidation of Cu+ into the less toxic Cu2+. Intriguingly, such regions in CueOs greatly differ in term of structure and Met content according to the microorganisms. The MetCop project aims at determining the role of CueO Met-rich domains in the mechanisms selected by various microorganisms along evolution to tackle copper stress. Two fundamental questions related to their involvement in copper homeostasis will be addressed: 1) To which extent Met-rich domains govern cuprous oxidase activity, hence copper detoxification? 2) What are the consequences of Met oxidation in Met-rich domains on copper tolerance? Through a multiscale and multidisciplinary approach, the MetCop project will allow to establish a clear correlation between i) structural features of Met-rich domains of a library of CueOs, ii) copper binding properties, iii) in vitro enzymatic activity and iv) in vivo copper resistance. The multiscale approach set in the MetCop project involves entire cells, periplasmic extracts, purified proteins and synthetic peptide models, allowing a back and forth iterative process between cellular and molecular scales to answer the two fundamental targeted questions. More specifically, the molecular basis of Cu binding to pseudopeptides designed from identified Met-rich domains of CueOs, will improve our knowledge on copper-Met coordination and guide mutation of specific Met in the Met-rich domains of CueOs from various microorganisms. Changes in cuprous oxidase activities as a function of Met-rich domain structural features will be correlated to in vivo copper resistance. MetCop thus ambitions to precisely determine how and which Met(s) in Met-rich domains are involved in copper binding and copper resistance. Beyond the involvement in cuprous oxidase activity, MetCop will search for a role of Met(s) in Met-rich domains in the protection against reactive oxygen species that can be produced in the presence of copper. It will finally investigate whether MsrP, a protein recognized to reduce oxidized Met(s), may participate to maintain CueO activities in vivo. The multidisciplinary approach is reflected by the panel of methodologies (some of them being especially set up in the MetCop project) carried out to determine the role of Met-rich domains of CueOs from different organisms in copper resistance: molecular biology, bioinformatics, biochemistry, chemical pseudopeptide design, theoretical methods and electrochemistry. This multidisciplinary approach is allowed thanks to a unique consortium with complementary expertise in i) genetics to study in vivo copper tolerance (LCB), ii) biophysics and biochemistry of redox enzymes including Cu-based metalloproteins (BIP), and iii) chemistry of copper binding to peptides (SYMMES). Such a multiscale, multidisciplinary approach is expected to provide new findings that will pave the way to the understanding of the evolutive selection of Met residues at specific position within proteins involved in copper homeostasis.

A bacteremia is caused by the presence of bacteria in the bloodstream, which is a sterile fluid in healthy people. This is one of the most common causes of death among hospitalized patients in intensive care units. Nowadays, in case of bacteremia suspicion, some blood is drawn from the patient and then "cultured", usually overnight, in experimental conditions favorable for bacteria multiplication in the vial. Then, and only after this enrichment step is completed, the bacterial identification can be launched. This latter step may last from few minutes and up to several days, depending on the nature of the bacterial contaminants, and also depending on the acceptable cost for its identification (the faster solutions, like PCR, are also the most expensive assays for the bacterial analysis). The assessment of the presence of bacteria, followed by their identification along with their susceptibility to antibiotics is the most important issue when facing a bacteremia. In this context, the fastest medical response, the higher survival chances. In order to better control both the critical time-lapse and cost issues, we propose to develop devices enabling a much faster response by using Surface Plasmon Resonance imaging (SPRi) of biochips DURING THE ENRICHMENT PHASE. The coupling of the multiplication phase with the bacteria detection into a single step will then significantly decrease the delay between the blood sampling and the response given to the doctor. One original aspect of our project is the use of A NEW KIND OF WIDE-SPECTRUM LIGANDS (THE ANTI-MICROBIAL PEPTIDES) FOR THE FUNCTIONALIZATION OF THE BIOCHIPS. The objective will be the use of a very small set of ligands (less than ten) for the arraying of biochips enabling the detection of the presence of any bacteria. Last but not least, an other important aspect of our project will be the inclusion, on the microarray, of another set of ligands (antibodies, phages and/or aptamers) HIGHLY SPECIFIC TO EACH MEMBER OF THE ESKAPEE PATHOGEN GROUP. This class of pathogen may lead to quite dramatic situations, and thus deserves a specific detection to drive the doctor to the best decision. Then, the BacUS project addresses several issues directly linked to a better fosterage of the patients in case of bacteremia, namely: a faster answer on the presence/absence of bacteria; the identification of any ESKAPEE pathogen if present in the sample; and cost-effective solution in regards to the current methods used so far. The BacUS project gathers three complementary partners: partner 1 (who is also coordinating the project) has a well-known experience in the operation of SPRi instruments for small molecules, bacteria or cell analysis as well in biochip microarraying with different ligands (proteins, peptides and aptamers); partner 2 is expert in the synthesis and characterization of peptide derivatives and also in the use of peptides for diagnostic purposes; partner 3 is a joint laboratory between the University and the Grenoble General Hospital and completes, every day, about 500 analysis, this partner is also expert in the qualification of new methods for bacteremia diagnostics. Besides a work package focused on the project supervision and coordination, the BacUS projects is composed of four other work packages. These tasks are increasing in complexity and will merge at the end of the project in order to test our method on real human blood samples. The overall risk taken by our project should be limited as BacUS is based on very encouraging preliminary results acquired by the three partners. We also wish to underline the fact that BacUS perfectly matches the objectives of the Défi 'Vie, santé et bien-être", and in particular of the axes 9 dedicated to the "Technologies pour la santé. On a more general aspect, this project aims at developing efficient and cost-effective solutions for diagnostics, which also meets the challenges defined by the national health authorities.

Nanotechnologies are the new industrial revolution of this century. The dissemination of engineered nanomaterials (NMs) in the environment is suspected. Agricultural soils can be contaminated via nanopesticides and spreading of sewage sludge. It implies that crop plants (first gate into food chain) may be exposed to NMs at large scale. Within this project, we plan to study the fate of TiO2 NMs in an agricultural ecosystem and their impacts on digestive health. Indeed, TiO2 is a large volume manufactured chemical. With an integrative approach we will investigate the toxicity, transfer and transformation of these NMs from soil to crop plants, primary consumer (snails), and up to humans (epithelial intestinal cells and mice). The originality of our study is to link different multidisciplinary approaches (plant, animal and cell biologies, biophysics and modeling) to study different TiO2 NM transfer through the whole food chain. The main objective is to identify the risk for food safety related with NM dissemination and optimize a "safer by design" synthesis of TiO2 material.

Photosynthesis is a fascinating source of inspiration to design innovative molecular devices for the conversion and storage of solar energy. Applications of interest however rely on multielectronic catalytic processes whereas light-driven processes are single-electron events in essence. Nature perfectly masters this apparent mismatch thanks to specific cofactors, able to accumulate and then to relay two electrons at a time by coupling these processes with proton transfers. PhotoAcc thus aims at developing novel charge photoaccumulation systems, by taking inspiration from such biological cofactors, flavins in particular. The project will benefit from the complementary expertise of the four internationally recognized research groups to (i) undertake their synthesis supported by a (TD)DFT-predictive approach to allow tailormade optoelectronic properties, (ii) to decipher their electronic properties by virtue of various electrochemical and spectroscopic characterizations, including advanced EPR techniques to identify the electron storage sites, and (iii) to assess their activity in light-driven multielectron/multiproton redox processes.

All solid-state batteries based on thiosulfate solid electrolyte hold the promise of safer and more energetic batteries, especially once coupled to Li metal anode and high voltage cathodes. Unfortunately, it was demonstrated in the literature that their electrochemical stability window is far from optimal being very narrow (less than 1V). This is causing severe chemical degradation upon oxidation/reduction of the solid electrolyte, showing that the solid electrolyte is a very active player in the solid-state batteries. The decomposition products generated during oxidation/reduction are causing drastic increase in cell resistance as well as some structural/chemical changes both hindering the long-term cycling of solid-state batteries. On top of that, the mechanical stability of the solid-state batteries is also questioned, as during cycling, the electrode breathing will lead to volume changes generating stress i) in the composite electrode materials, ii) at the interfaces, and iii) in the electrolyte. The stress propagation will be soon translated into fractures at all pre-cited levels, affecting the lithium transport mechanism within the cell causing premature cell failure. As described in the literature, this chemo-mechanical degradation looks unavoidable. However, the literature is relying on the investigation of half-cells/full-cells to explain the chemo-mechanical degradation, but the solid electrolyte alone and especially its sintering/shaping could also be the main responsible of most of the pre-cited issues. Poor sintering, as an example, promotes chemical degradation and voids propagation, thus, getting a deep understanding of the sintering process prior to any electrochemical cycling is of utmost importance. We propose a multiscale approach based in operando characterizations at the laboratory scale and at large scale facilitate (synchrotron and neutrons) to fully understand the sintering process of the electrolyte and in particular to establish the relationship between structural/chemical/morphological/electrochemical parameters as a function of the pressure/temperature. To apply this methodology, novel special electrochemical cells will be developed to perform advanced operando-based techniques. Neutron diffraction will be used to follow the structural evolution during sintering process as a function of temperature/pressure, whereas X-ray tomography and FIB-SEM will be employed to follow the evolution of the porosity as a function of the pressure/temperature. Quasi elastic neutron scattering (QENS) owing to the contrast of lithium isotopes will provide information about Li ion transport whereas chemical decomposition will be investigated by X-ray absorption spectroscopy, etc. Once the sintering process will be fully understood, the solid electrolyte fully optimized will be then transferred to half-cell configuration (vs. Li metal) and the same methodology will be applied. Neutron imaging technique will be added to the pool of operando techniques to follow the Li ion transport as a function of cell cycling. Results from morphology/structure/chemistry gathered at this stage will be used to develop proper coating strategy and buffer layer to ensure electrochemical/chemical/morphological/structural stability. Again, once this goal will be reached, full cell investigation combining high voltage cathode vs. Li metal will be undertaken following the same operando-based approach. The results collected and obtained through this OpInSolid project will shed light on a forgotten player, the solid electrolyte. Based on the outcome, several strategies will be developed to tackle chemo-mechanical issues in sulfide-based solid state batteries.