To carry out their activities, Research Teams of the Frédéric Joliot Institute for Life Sciences have developed high-profile technological platforms in many areas : biomedical imaging, structural biology, metabolomics, High-Throughput screening, level 3 microbiological safety laboratory...
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All the news of the Institute of life sciences Frédéric Joliot
Laboratory | Chemistry | Nanosciences | MRI | Medical imaging
Team LeaderBernard Rousseaubernard.firstname.lastname@example.org
Deuterium/tritium labeling of biomolecules starting from synthetic precurors is usually time and atom-consuming, expensive and sometimes erratic. Biology but also therapeutic innovation both need the development of more robust, versatile and reliable methods for isotopic labeling that can use the native molecule without preliminary modification. In collaboration with Dr. B. Chaudret at INSA Toulouse (CNRS/Univ. Paul Sabatier), we focused our interest on the study of ruthenium nanoparticles-catalyzed H/D and H/T exchanges. In particular, we demonstrated the unprecedented potential of these nanoparticles to catalyze the H/D isotopic exchange on a series of aza compounds and sulfides (including polyfunctionalized chiral molecules) in very mild conditions (1-2 Atm, 20-55°C) and in various solvents. Our results, explained by extensive DFT simulation, show that the exchange reaction occurs through an unprecedented mechanism which implies a three ruthenium atom catalytic core and an enantiospecific C‒H activation. This strategy was shown to be fully applicable for the stereoretentive deuterium labeling of drugs, amino acids and peptides etc. Moreover, our group also maintains an expertise in terms of tritium labeling of biomolecules through more classical pathways, in particular in the framework of collaborative research activities (ie. ERC Ternanomed with Prof. P. Couvreur).
Atomic scale resolution of the 3D structure of small molecules interacting inside a huge molecular complex (self-assembly, membrane peptide, non-crystallized ligand-macromolecule complex) is a prerequisite to understanding their chemical and/or biological activity. Presently, there is no efficient method to solve the atomic structure of such non-crystalline complexes. In collaboration with Drs. M. Paternostre (CNRS) and T. Charpentier (CEA), we initiated the development of a new strategy which combines tritium labeling, solid-state tritium NMR (spin ½) and molecular modelling in order to resolve the structure of non-crystalline molecular complexes and assemblies. The proof of concept was done on small rigid molecules and showed it is possible to measure interatomic distances up to 14 Å with an unprecedented precision. Successive determinations of intramolecular inter-tritium distances on crystalline Phe-Phe, the structure of which has been resolved by X-ray diffraction, is now under progress and will be then applied to the mysterious Phe-Phe nanotubes. This new strategy of 'crystallography by NMR' will be also used to solve the atomic structure of other biologically relevant nano-objects such as antimicrobian peptides, anti-amyloid compounds etc.
Nanodiamonds are nanosized carbon frameworks which display particular structures and properties. Recent studies suggest that after hydrogenation, nanodiamonds can be used as molecular scaffolds for the design of nanocatalysts capable of performing particular chemical reaction. They can also be used as nanodelivery systems carrying drugs and other bioactive molecules. Moreover, the fluorescent properties of certain nanodiamonds suggest that they could be used as molecular probes for diagnostic imaging. In cooperation with Drs. T. Charpentier and J-C. Arnault (CEA), we are presently investigating the surface chemistry of nanodiamonds reduced by a tritium plasma in order to determine, by tritium solid-state NMR, the position and number of hydrogenated motifs usable for engineering the nanodiamond surface.
Initiation of plasma experiments (tentatively in 2025) in the international experimental thermonuclear fusion reactor ITER settled in Cadarache should allow to make the transition of experimental plasma physics to full-scale electricity-producing fusion power plants. However plasma ignition inside the tokomak necessitates supplementary investigations about the potential production of tritiated tungsten particles by plasma abrasion of the beryllium-tungsten blankets. In particular, few is known about the capacity of these particles to absorb and further release tritium. Moreover, their possible (radio)toxicity, in particular for lung, has to be assessed. We have been investigating both the absorption and release of tritium gas by various tungsten powders (from 30 nm to 30 mm diameter) in collaboration with several CEA teams supporting the ITER project, in particular Drs. V. Malard (DSV) and C. Grisolia (DSM) but also Dr. F. Gensdarmes (IRSN) and academic partners Drs. D. Vrel (LSPM- Univ. Paris 13) and G. Dinescu (NILPR-Bucarest). The toxicity of the tritiated particles will be evaluated on cultured pulmonary cells in close cooperation with the University of Aix-Marseille and CEA/Cadarache.
In vivo Magnetic Resonance Imaging (MRI) is a routine diagnostic technique which allows the real-time whole-body volumetric imaging of patients. Despite its remarkable spatial resolution classical MRI, based on proton NMR principles using gadolinium complexes as contrast agents, has a low sensitivity which strongly limits MRI molecular imaging. Hyperpolarized xenon-129 MRI is an interesting alternative to proton/gadolinium MRI owing to the fact that :
However, xenon must be encapsulated inside cage-molecules, in particular cryptophanes, the synthesis of which has been investigated by our group in collaboration with Dr. T. Brottin (ENS-Lyon). In particular, we have developed in cooperation with Dr. P. Berthault (CEA) a series of cryptophane-based molecular probes usable for the detection and dosing of metal cations in biological fluids, the monitoring of oxidative stress and the detection of particular proteins. Presently, the translational application of this technology for imaging non-small-cell lung cancer is in progress in collaboration with Drs. P. Berthault, S. Simon/E. Ezan (CEA), and Prof. E. Deutsch (IGR).
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.