Defining the role of stress granules (SG) in RNA stability and translation.

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Early during evolution, cells have developed very sophisticated mechanisms to detect, respond and adapt to stressful environment. Resistance and adaptation to various stresses, notably through repair mechanisms and reprogramming of gene expression, are fundamental determining factors in the behavior of metazoan cells. The cellular responses to stress involve signal transduction mechanisms that are initiated at the lesion sites (i.e. DNA, protein, cytoskeletal polymeric structures or organelles) and then propagated to the core cellular machineries to generate a highly coordinate cellular response. Therefore, the ability of cells to cope with various stresses relies on complex mechanisms that are finely tuned spatially and temporally, exhibit high intercellular heterogeneity, and often involve the assembly of transient and highly specialized subcellular structures. ******The applicants Mazroui, Huot, Fradet-Turcotte and Lavoie are early, mid-career, and senior female/male principal investigators at Université Laval, who made significant contributions in elucidating various aspects of the cellular responses to stress, including DNA damage response, stress-induced RNA or protein compartmentalization and translation, cell division and death, and cell adhesion and motility. All four applicants have developed NSERC-funded programs that heavily rely on imaging of dynamics subcellular structures in response to stress. The research programs of the applicants would significantly benefit from a more sensitive and rapid confocal system for the acquisition of large imaging datasets at high resolution. This application is to request funding for a first upgrade of our existing Zeiss LSM 700 system to a high performance LSM 900 confocal system. This equipment would tremendously accelerate knowledge on Cell Biology areas with widespread relevance, while maintaining high quality standards in HPQ training using state-of-the art technologies. ******Our main scanning confocal system, the LSM 700, was acquired 10 years ago and is not suitable to detect weak near-to physiological proteins or to quantify subcellular structure dynamics, as it suffers from a lack of sensitivity and scanning speed. We propose to replace the confocal head, the detectors as well as the laser module to benefit from major advantages of the new generation LSM 900. The acquisition of a sensitive confocal system optimally designed for live-cell imaging is urgent, not only for our groups to maintain their competitiveness, but also to sustain the high-quality training standards for HPQ with state-of-the-art technologies.****** **