Physiological Function of Rhomboid Protease RHBDL4.

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Evolutionary-conserved protein families withstood evolutionary pressure likely because they carry essential and fundamental functions within the cell or an organism. One such protein family are formed by rhomboid proteases. They are expressed throughout the mammalian system in different tissues, however, their functions remain largely unknown. Discovering such functions has the potential to identify important biological pathways. Part of my research program is to uncover the function of rhomboid proteases. In our NSERC Discovery grant, we investigate the regulation and mechanism of such rhomboid proteases and we have made great progress. Our research has led us to focus on one particular rhomboid protease named RHBDL4. Our preliminary evidence shows that RHBDL4 may play a role in the cellular response to low oxygen levels, termed hypoxia. Responding to hypoxic stress is an essential cellular ability to guarantee survival of the cell. Oxygen depletion can occur transiently or chronically during normal body operation and therefore, hypoxia-response mechanisms need to act quickly and be available to all cells. Our research is therefore at a critical point where we are just about to definitely proof the physiological function of RHBDL4. However, to be able to do this, we required specialized equipment that will allow us to properly cause hypoxic conditions in vivo and in vitro. We therefore request herein the funds to purchase such specialized equipment, i.e. a hypoxia-work station system. Highly qualified personnel in my laboratory will be using this equipment to gain insight into RHBDL4 biology under normoxia and hypoxia.