Mechanism and regulation of perforin function

穿孔蛋白是在细胞毒性淋巴细胞中发现的溶细胞蛋白。它在破坏病毒和病原体感染的细胞以及肿瘤细胞中起着重要作用。人和实验动物中的穿孔蛋白缺乏导致对许多病毒感染的抵抗力丧失，并显著增加自发肿瘤形成的机会。虽然穿孔素在二十年前首次被表征，但其作用机制仍然未知。目前的拨款提案将利用我们实验室最近的一些关键技术进步，使我们能够研究穿孔素功能的机制和调节。我们最近在该领域取得的进展使我们在进行这些研究方面处于领先的国际地位。从更广泛的意义上讲，拟议的研究将对我们理解细胞毒性淋巴细胞调节免疫应答的机制和免疫稳态产生直接影响。它还将提高我们对各种病原体防御机制的理解，并将为免疫系统在保护生物体免受癌症侵害中的作用提供更多见解。

Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise on some recent key technological advances in our laboratory that are enabling us to investigate the mechanisms and the regulation of perforin function. Our recent advances in the field put us in a pre-eminent international position to conduct these studies. In broader terms, the proposed studies will have an immediate impact on our understanding of the mechanisms of cytotoxic lymphocyte regulated immune response and on immune homoeostasis in general. It will also improve our understanding of defence mechanisms against various pathogens and will provide more insight into the role of immune system in protection of the organism against cancer.