Physiological Function of Rhomboid Protease RHBDL4.

进化保守的蛋白质家族经受住了进化的压力，可能是因为它们在细胞或有机体中承担着必要和基本的功能。一个这样的蛋白质家族是由菱形蛋白酶形成的。它们在整个哺乳动物系统的不同组织中表达，然而，它们的功能在很大程度上仍然未知。发现这些功能有可能确定重要的生物学途径。我研究计划的一部分是揭示菱形蛋白酶的功能。在我们的NSERC发现基金中，我们研究了这种菱形蛋白酶的调控和机制，并取得了很大进展。我们的研究使我们专注于一种名为RHBDL4的特殊菱形蛋白酶。我们的初步证据表明，RHBDL4可能在细胞对低氧水平（称为缺氧）的反应中发挥作用。对缺氧应激的反应是保证细胞存活的基本细胞能力。在正常的身体运作过程中，氧的消耗可能是短暂的，也可能是长期的，因此，缺氧反应机制需要迅速发挥作用，并对所有细胞都有效。因此，我们的研究正处于一个关键时刻，我们即将明确证明RHBDL4的生理功能。然而，为了做到这一点，我们需要专门的设备，使我们能够在体内和体外适当地造成缺氧条件。因此，我们在此要求资金购买这种专门设备，即缺氧工作站系统。我实验室的高素质人员将使用该设备深入了解RHBDL4在常氧和缺氧条件下的生物学特性。

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.