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The team’s major interest is in the cellular responses to stress, which is fundamental to pathology in any cell type. The team's focus is the analysis of the role of cryptochromes - which are flavoprotein signalling molecules found throughout the biological kingdom (prokaryotes and eukaryotes). The cryptochrome proteins themselves are highly conserved between species and appear to have similar functions; their protective role in stress response in animal systems is currently a new and emerging field. In the project, a variety of model systems, in vitro and in vivo, will be examined to identify how cryptochromes protect against stresses, with special emphasis on identifying their molecular targets (interacting partners) and the mechanisms whereby cryptochromes activate these targets. In addition to ongoing studies in plants, novel roles for cryptochrome in animal stress responses will be tested for in the drosophila and mammalian cell culture models. Novel results show that the mechanism of activation and pathways of response to stress mediated by cryptochromes may be highly conserved across species. Experiments conducted with transgenic flies expressing human cryptochrome HsCRY1 show that both human and drosophila cry may regulate some of the same genes and promoters. Hence, fundamental discoveries on cry activation in plants, flies, or in mammalian cell cultures may reveal conserved mechanisms that protect against cellular stress and which will be directly applicable to treatment of age-related pathologies in humans. . The ultimate goal of the research proposal is to target cryptochromes as a potential therapeutic tool. The characteristic of cryptochromes that makes them of particular interest from a potential therapeutic point of view is that they may be activated by light and magnetic fields. These are mild, non-invasive treatments that would reduce the need for expensive drugs, with potential harmful side-effects, or invasive surgical procedures. . Therefore, the cryptochrome proteins themselves will be isolated and studied at the molecular level for function and mechanism of activation by light and other environmental signals such as applied magnetic fields. The future project therefore divides into 4 associated themes: (1) characterization of novel signaling pathways of plant cryptochromes in stress and ageing (2) characterization of novel pathways of animal cryptochromes in stress, (3) regulation of cryptochromes by the magnetic field - the extension of magnetic fields as potential therapeutic tools to synaptic formation and/or protection from cellular stress responses and 4) structure-function analysis of isolated plant and animal cryptochromes with a view to controlling them by light or other signals. These studies thus extend the fundamental molecular bases of the Unit’s research by introducing a novel type of receptor and provide a potential translational project by testing cry as a target for non-invasive therapeutic tools. .

B2A UMR 8256 @Février 2014