NSERC grants at Laurentian University Subventions du CRSNG `a l ...

48Éric GauthierMolecular control of apoptosis in mammalian cellsA grant of $29,300 per year.Une subvention de 29 300 $ par année.Discovery Grant – Subvention à la découverteThe use of mammalian cell lines for the industrialproduction of biomedical or pharmaceuticalproducts is hampered by the high cellularsensitivity to culture-related stresses. Ourresearch program is centered on the molecularand cellular mechanisms of cell suicide (apoptosis)and on the use of cell death inhibitors incellular engineering. This grant application will describe two main projects:1. A detailed analysis of the effect of the anti-apoptotic protein Bcl-xLon cell culture behaviour and productivity. Bcl-xL is a protein whoserole in the cell is to prevent the untimely triggering of cell suicide. Severalstudies have shown that Bcl-xL could be used to protect cells againstapoptosis, leading to increased productivity. In this proposal, we arguethat one major limitation to the use of Bcl-xL in mammalian cells ofbiotechnological interest is the lack of understanding of the regulationof Bcl-xL in these cells, as well as the paucity of information currentlyavailable on the effect of the over expression of Bcl-xL on cell behaviourand the cellular response to nutrients. The work proposed here will leadto a thorough characterization of the function and regulation of Bcl-xLin mammalian hybridoma cells.2. The generation of a Hybridoma Gene Expression Profile Database.A major factor limiting the applicability of cellular engineering to improvemammalian cell culture bioprocesses is the current lack of informationon the changes in gene expression occurring in cultured cell lines.We propose to establish a Hybridoma Gene Expression Profile Databaseusing the latest DNA-Chip technologies. This information will allow researchersto tailor their cellular engineering strategies to their favorite cellline, leading to optimal improvements in cell viability and productivity.