Structural and Biochemical Analysis of Telomerase Function

描述(由申请人提供)：端粒酶的不适当激活与高达90%的人类癌症中出现的细胞不受控制的增殖有关。自20世纪90年代中期首次在人类肿瘤中发现端粒酶以来，科学家一直将该酶视为开发广泛有效的抗癌药物的理想靶点。端粒酶在癌症中的重要作用使其成为重要的药物靶点。我提出了一种结构生物学的方法来研究端粒酶的功能及其在人类疾病中的作用。结构数据在解释和设计生化和生物物理实验方面可以证明是无价的。它也可以成为药物发现的一个非常强大的工具。我研究计划的长期目标是使用结构生物学，结合生物化学来了解端粒酶是如何复制端粒末端的，并将这些信息应用于抗癌治疗的追求。 与公共健康相关：端粒酶与癌症、心血管疾病和衰老有关。因此，我们的目标是阐明这种酶的生物学功能，并利用这些信息来对抗癌症和与年龄相关的疾病。

DESCRIPTION (provided by applicant): Inappropriate activation of a single enzyme, telomerase, is associated with the uncontrolled proliferation of cells seen in as many as 90 percent of all human cancers. Since the mid-1990s, when telomerase was first identified in human tumors, scientists have eyed the enzyme as an ideal target for developing broadly effective anti-cancer drugs. The important role of telomerase in cancer makes this enzyme an important drug target. I propose a structural biology approach to examine the function of telomerase and its role in human disease. Structural data can prove invaluable in explaining, as well as designing, biochemical and biophysical experiments. It can also be a very powerful tool for drug discovery. The long-term goal of my research plan is to use structural biology, in conjunction with biochemistry to understand how telomerase replicates telomere ends, and to apply this information to the pursuit of anti-cancer therapies. PUBLIC HEALTH RELEVANCE: Telomerase has been implicated in cancer, cardiovascular disease and aging. For this reason, our goal is to elucidate the biological function of this enzyme and use this information to combat cancer and age-related diseases.