The DECAP project is focused on the development of innovative hydrogels prepared from polymeric materials for external actinide sweet decontamination. This breakthrough exploratory research project will bring major benefits in both the field of defense, and civil and industrial research. The objective is to prepare new chelating macromolecules able to complex radionuclides with the controlled synthesis of complexing copolymers. The latter are based on poly(e-caprolactone)s (PCLs) functionalized with bis-phosphonic acid groups, able to efficiently complex radionuclides, and poly(ethylene glycol) (PEG). They will lead to innovative hydrogels allowing treating very rapidly, and efficiently a contact contamination without wound, without diffusion under the skin. It is important to mention that PCLs and PEG polymers are both biocompatible and approved by the FDA. These hydrogels, formulated and characterized by rheology, are adapted for their use in a typical field environment, without spreading out over the skin and without the need of rinsing with water. So, they will be more efficient, easy to carry, and final waste will be minimized. A consortium has been worked out, associating four academic partners, selected for their background in specific areas: synthesis and characterization of biopolymers, and phosphorus-based materials, partitioning chemistry, materials dealing with nuclear concerns, study of interfacial phenomena at the liquid-liquid and solid-liquid interface, and formulation and physic-chemical study of polymers for pharmaceutical applications. This appropriate consortium will efficiently interact to carry out the following different stages: (i) elaboration of e-caprolactone monomers, judiciously functionalized by bis-phosphonated ester groups, precursors of bis-phosphonic acid functions, (ii) synthesis of biocompatible bis-phosphonic acid-based poly(e-caprolactone)s, (iii) formulation of hydrogels based on copolymers determined as biocompatible and study of these hydrogels (rheological properties, cutaneous penetration), (iv) efficient complexation of radionuclides that we can recover in nuclear accidents (in nuclear power plants or during dismantling) or in terrorist attacks against military or civilian. First, we will study uranium (VI) and thorium (IV) that are valuable components as they are easy to manipulate to establish proofs of concept. These two elements are good models to “mimic” neptunium (V) and plutonium (IV), respectively, that are much more dangerous and that we will also study for some specific experiments. This project perfectly fits with the requirements of thematic 7 “Biologie et Biotechnologies” dealing with current and emerging nuclear risks of deliberate or accidental origin. It deals with sub-topic “decontamination”, in particular corporal decontamination (external).

The emergence of important viral human pathogens (eg., Dengue, Zika, SARS, MERS, Ebola viruses) cause substantial health and economic burden. These RNA viruses can rapidly evolve and escape antiviral responses by hiding their RNAs from detection by antiviral sensors. Their viral replication/transcription complex contains essential enzymes involved in RNA synthesis (polymerase) and epitranscriptomic RNA modifications (RNA methytransferases and sometimes exonucleases) responsible for luring the host cell. For selected viruses, here Flaviviruses and Coronaviruses, using our preliminary data and experimental systems developed in the 4 partner labs, we will address 1) the enzymology of RNA processing: synthesis, tagging, correcting, and evolving vRNA; 2) The innate immunity response elicited by RNA products of model viruses in infected cells; 3) the structural basis for the genome evolution machinery. Results aid antiviral drug-design, and connect the mechanistics of viral epitranscriptomic RNA modification to innate immunity.

The majority of hormones and neurotransmitters communicate information to cells via G protein-coupled receptors (GPCRs). The large number of biological functions they control also makes these membrane receptors one of the most prominent families of pharmacological targets in biomedicine. GPCRs exhibit complex signaling behaviors. Indeed, a single receptor can activate both G protein-dependent and G protein-independent pathways. The latter result from the coupling of the receptor to a major family of signaling proteins, arrestins. Although arrestin-dependent signaling is a major component of GPCR functioning, we are just beginning to grasp its mechanistic bases, even for the best-studied GPCRs. The current model of GPCR:arrestin interaction, the so-called phospho-barcode model, states that, upon activation by their ligand, GPCRs get phosphorylated at different sites on their C-terminal domain, and this impacts on the way arrestin interacts with these regions, in turn affecting its conformation and, ultimately, the intracellular signal arrestin triggers. However, the experimental demonstrations of this mode of functioning are still scarce. Interestingly, the GPCR C-terminal domains appear to present all the structural, dynamic and functional characteristics of intrinsically disorder regions (IDRs), a family of proteins whose specific role in fundamental signaling and regulation processes started to be revealed very recently. In GPCteR, we propose an analysis of the molecular mechanisms underlying arrestin:GPCR interaction, and hence arrestin-dependent signaling, using a combination of state-of-the-art biophysical methods, namely solution-state Nuclear Magnetic Resonance, Small Angle Neutron or X-ray Scattering and fluorescence spectroscopy. These methods will be applied to a full range of model systems of increasing complexity composed of isolated GPCR C-terminal peptides, purified arrestins, and kinases and full-length receptors assembled into membrane-mimicking systems. Three different GPCR systems, the ghrelin, the vasopressin V2 and the B2-adrenergic receptors will be used as models. Besides the fact that these receptors are representative of the two different classes of arrestin binders, they are also important pharmaceutical targets due to their major role in fundamental physiological and patho-physiological processes. We expect these studies to illuminate the structural and dynamic keys required for the interaction of GPCRs with arrestins and, as such, to help us understand how G protein-independent signaling proceeds. This is not of academic interest only as our studies will likely provide also essential information to guide the rational design of peptide mimetics that could interfere with this interaction and thus be used as selective drugs and/or pharmacological tools to only affect receptor:arrestin interaction, to modulate specific signaling cascades, and therefore to impact on a limited set of all the biological effects controlled by GPCRs.

The predictable nature of nucleic acid hybridization offers a simple and cutting-edge platform to program assemblies with emerging function. While nucleic acids are known to be versatile biomolecules that play a crucial role in regulating gene expression in various organisms, the burgeoning use of nucleic acids as a material to organize the precise arrangements of specific molecules marked an important milestone in the relatively young history of smart bioarchitectures. While functional DNAs and RNAs hold great promise for future applications in nanotechnology and bioanalysis, in this project, we set out to design and study functional stimuli-responsive nucleic acids-based architectures, capable of self-assembling by formation of reversible linkages. Based on the complementary expertise of the two partners, the main goal of the present project is to induce the self-assembly of small aptamers, ribozymes and aptazymes from short DNA or RNA fragments modified with a 5’-boronic acid, and to demonstrate their functionality. With respect to possible application of our results, we see potential in the field of biosensing; a system composed of a collection of 5'-boronic acid modified oligonucleotides could be used for detection/sensing of a chosen analyte. We consider our work being relevant not only for the field of biosensing, but moreover for investigations into RNA world scenarios, where self-organization and self-assembly of smaller oligonucleotides to larger functional entities might have played an important role. As has been hypothesized, boronic acids forming reversible linkages with the cis-diol of ribose may have preceded RNA phosphate linkages, and the demonstration of boronic acid linkage based self-assembly would strongly support this idea.

Used since prehistoric times, leather is the oldest material invented by man to protect himself from external conditions. It has now become a popular aesthetic material for fashion and luxury. Today, more than two billion square meters are produced worldwide every year. Organised around a sector ranging from tannery to leather goods, footwear and furniture, the French leather industry employs more than 130,000 people in 100 different professions. However, the leather industry must face societal, environmental and regulatory challenges that could trigger its decline if nothing is done. A major and undeniable advantage is that leather is a natural material recycled from a waste product: animal skin from the food industry. However, the transformation of putrescible hide into rot-proof leather requires the use of chemicals. Metals, mainly chromium, are among the chemicals used. Although not dangerous, chromium III used for tanning (84% of tanned leathers) can oxidize to chromium VI creating a risk of skin allergy. Since 2015, REACh Regulation No. 1907/2006 has imposed a threshold of 3ppm for chromium VI in leather. Already low, this threshold could, in the coming years, even increase its value to 1ppm, making the manufacture of chrome leathers difficult to maintain. Alternatives have already been offered to tanners. Tanning agents such as zeolite (aluminum silicate) give convincing results. However, aluminum, just like chromium and metals in general, suffers from a bad image in the eyes of consumers. In addition, leathers tanned with vegetable tannins do not meet the specifications of chrome-tanned leathers. Aldehydic tannins and other organic compounds are still struggling to find their place between regulatory constraints and market expectations. As a CPDE, CTC's objectives are to support the leather industries in their search for technical, innovative, environmentally friendly and economically viable solutions to meet these challenges. The Objectives and Performance Contract, signed between CTC and its supervisory authority, the Directorate General for Enterprise (DGE), demonstrates this. The SICLE2 Industrial Chair is an integral part of this approach. CTC, the University of Montpellier and BioWooEB CIRAD laboratory wish to combine their skills and obtain unique expertise in the chemistry of biomolecules, materials, agronomy and leather trades to unlock the technical barriers and enable the leather industry to be more sustainable and sustainable. Structured around two axis of research, SICLE2 is based on a novel silicon-based tanning process (non-toxic) patented jointly by CTC and the University of Montpellier. The first axis concerns the development of efficient and environmentally friendly tanning methods as well as the development of new leathers with innovative functionalities. Silicon tanning also paves the way for easier recovery of tanning by-products, effluents, and the development of new materials. These aspects are the subject of the Chair's second major research axis, which may be of interest to other industrial sectors such as agriculture, agri-food and construction. These two lines of research will be nourished by a detailed understanding at the molecular level that will make it possible to unlock the obstacles encountered. Twelve young researchers will be trained as part of SICLE2, thus consolidating a partnership with two engineering schools. Through dedicated training, SICLE2 will support the sector's players in changing industrial practice. Bringing together both economic and environmental issues, SICLE2 is positioned as a national reference to meet the expectations of the leather industry.