SENSE AND PURIFY will transform water treatment by developing an integrated device that measures the organic and pathogen contaminants present in real waste water (URV, UWC, NU, DCU) then destroys recalcitrant organics and pathogens using a “wireless” advanced oxidation strategy (DCU, NU, UWC) and confirms the quality of the treated water (URV, NU, DCU). Unlike all existing approaches where reactive species capable of destroying organics and bacteria occurs only at an electrode surface, our approach creates highly destructive/energetic radicals throughout the entire volume of the waste water stream dramatically decreasing the time required to destroy the impurities and ensuring the production of clean water. This eco-innovative TRL 4/5 technology brings together key recent advances by team members to create significant advantages including lower capital, operations and maintenance costs, reduced energy consumption, higher conversion efficiency, easier operation, better effluent water quality, and lower waste production. To accelerate and enhance its industry relevance, we will demonstrate the industrial utility of the approach by creating a waste water treatment reactor for the local purification of production water in the food and pharmaceutical industries as well as treating municipal water.

The objective of this project mixing organic chemistry and virology is to develop Adeno-Associated Vectors (AAVs) chemically modified to improve its safety and efficacy. AAVs are now becoming therapeutic products, however, clinical trials showed critical limitations: high doses are required to achieve therapeutic efficacy and off-target tissue transduction. ChemAAV will allow optimal cell targeting with enhanced therapeutic index and restricted biodistribution. These improvements will be obtained by chemical coupling of a ligand with targeting properties at the surface of the AAV, exploiting natural amino-acids of the capsid. The advantage of chemistry is the possibility to modify the AAV capsid with synthetic polymers, peptides, carbohydrates or even lipids that cannot be incorporated genetically. We will focus on two target cells for the proof-of-concept studies; hepatocytes and hematopoietic stem cells, with direct applications for liver, blood disorders, and immunodeficiencies.

The objective of the proposal is to investigate the potential of a brand-new imaging technique, Spectral Photon Counting Computed Tomography or SPCCT (currently in development, to detect, characterize and monitor neurovascular and cardiovascular disease), for the visualization of injectable calcium phosphate cements (CPC) used in bone reconstruction surgery. Hence, combination of the contrast agents designed for SPCCT with CPC will be investigated to allow good visualization of the cement, while retaining suitable ergonomic, mechanical and biological properties for their practical use in bone surgery. Compared imaging results will be performed, to demonstrate that SPCCT provides unique advantages for the in vivo monitoring of the degradation of CPC implants, in comparison with other imaging techniques, in particular CT-scan. For that purpose, a preclinical animal model of spine fusion will be used, since the possibility to early detect fusion failures is a critical issue for this indication. The proposal will also investigate the potential of SPCCT to target and visualize the inflammatory process occurring during bone repair. Finally, the expected results might also open the way to the image-guided implantation of theses cements, via minimally invasive procedures.

Conjugation of polymer scaffolds with multiple copies of a sugar ligand has become a popular approach for improving protein targeting. While multivalent linear polymer scaffolds allow an enhanced potency, also called “statistical binding”, where a nearby ligand quickly replaces the bound ligand due to its proximity, their selectivity can be limited. To overcome this, the CyClick project aims at designing new multivalent cyclic polymer ligands with dramatically enhanced potency and selectivity toward a protein target. For this purpose, the CyClick project consortium is composed of three complementary teams at Le Mans University, Nantes University, and GLYcoDiag SARL. The synthetic approach retained for the CyClick project consists in developing a versatile and robust method for the synthesis of well-defined multivalent cyclic polymer ligands in high purity and useful quantities. The cyclic polymer scaffold will be synthesized by ring-expansion metathesis polymerization (REMP) of cyclo-alkenes having a clickable moiety, and post-functionalized with biologically relevant carbohydrate ligands by click chemistry. Clickable azlactone functionalities have been chosen as they show high reactivity toward amine nucleophiles with full atom economy in a broad range of organic solvents as well as in aqueous solution at room temperature without generating by-products, and are compatible with ruthenium-based catalysts used for REMP. Ligands of carbohydrate-binding (lectins) or carbohydrate-processing proteins (glycosidases) involved in a host of biological events such as fertilization, cell-cell communication and the adhesion of pathogenic bacteria, fungi or viruses to human cells have been selected. Optimized carbohydrate and iminosugar ligands that proved particularly efficient for the multivalent inhibition of model or therapeutically relevant lectins and glycosidases will be clicked on the cyclic polymer scaffolds. This two-steps strategy has the particular advantage to allow the creation of diverse multivalent libraries from a single polymer platform and the large-scale production of multivalent ligands. The binding affinity of the so-obtained multivalent ligands for lectins and glycosidases will then be evaluated with the GLYcoPROFILE® technology developed by the industrial partner of this project: GLYcoDiag SARL. The motivation underlying this project is twofold: on one hand, the tuning of the rigidity of the scaffold and inter-binding site distances to allow an unprecedented match with the protein target through the use of different cyclo-alkenes with varying rigidity as well as the possibility to perform their alternating copolymerization; on the other hand, the synthesis of the linear equivalent counterparts by ring-opening metathesis polymerization (ROMP) will give the opportunity to study the impact of the scaffold topology on the strength and specificity of glycans recognition and the concomitant biological properties. This project will pave the way to a new class of cyclic polymer ligands with unprecedented biological activity. For the industrial partner, this project will bring new expertise in carbohydrate-binding proteins interaction analyses from cyclic polymer ligands. Last but not least, the Cyclick project will provide a chemical methodology to access a new type of (cyclic) polymers displaying specific physiochemical parameters with potentially high interest in polymer industry.

Among the various elements present in organic molecules, oxygen plays a key role in many functional groups, and its isotopic labelling often provides determinant mechanistic evidences in chemical reactions and biological studies. Whereas using singlet oxygen (1O2) is a convenient strategy to incorporate oxygen atoms in organic compounds in extremely mild conditions, the direct transfer of the existing conditions involving large excesses of O2 is too costly for practical applications in isotopic oxygen labelling. In this context, the DelivrO2 project proposes the development and the use of new endoperoxides that will allow the efficient and temporally / spatially controlled releases of stoichiometric amounts of isotopically labelled [*O]1O2 for both synthetic and biological applications.