Drosophila Telomere Function

果蝇端粒功能

• 批准号: 7146621
• 负责人: KENT G GOLIC
• 金额: $ 31.02万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7146621
• 关键词: Drosophilidae; aging; cell cycle; cell growth regulation; cell senescence; chemical structure function; confocal scanning microscopy; green fluorescent proteins; nucleic acid structure; telomere; transfection /expression vector

DESCRIPTION (provided by applicant): The loss of telomeric DNA in human somatic cells, arising from of the lack of telomerase expression, causes cellular senescesce and is associated with aging. Escaping the normal consequences of telomere loss is a critical step in the progression of cancer. Thus, understanding the normal mechanisms of cellular response to telomere loss and mechanisms that bypass the normal response are important for understanding, and possibly treating, cancer and ailments associated with aging. This work will use the model organism Drosophila melanogaster to investigate these issues. Preliminary experiments show that the response of Drosophila cells to telomere loss is very similar of the response of human cells to telomere loss, and is likely to be highly informative. There are 4 primary goals of this work. The first goal is to quantitatively characterize the response of Drosophila somatic cells to loss of a single telomere. A method for tracking the fate of cells that have lost a telomere will be implemented for this purpose. Second, the genetic control of these responses will be investigated. The third goal is to determine the mechanism of response of male germline cells, in which the non-telomeric chromosome ends are efficiently healed. The final goal is to investigate the nature of the healed chromosomes, to determine whether the telomeres they posses provide a normal protective function to the end of the chromosomes, or whether they are only partially functional. These investigations will provide an understanding of the machinery used to recognize telomere loss and to direct the response of cells to such loss. The differences between somatic and germline cells may provide insight into similar differences found in human cells.

描述（由申请人提供）：由于端粒酶表达缺乏而导致人类体细胞中端粒DNA的丢失，导致细胞衰老并与衰老相关。逃避端粒丢失的正常后果是癌症进展的关键一步。因此，了解细胞对端粒丢失反应的正常机制以及绕过正常反应的机制对于理解并可能治疗与衰老相关的癌症和疾病非常重要。这项工作将使用模式生物果蝇来研究这些问题。初步实验表明，果蝇细胞对端粒丢失的反应与人类细胞对端粒丢失的反应非常相似，并且可能包含大量信息。这项工作有 4 个主要目标。第一个目标是定量表征果蝇体细胞对单个端粒丢失的反应。为此目的，将实施一种追踪丢失端粒细胞命运的方法。其次，将研究这些反应的遗传控制。第三个目标是确定雄性生殖细胞的反应机制，其中非端粒染色体末端得到有效愈合。最终目标是研究愈合染色体的性质，以确定它们所具有的端粒是否为染色体末端提供正常的保护功能，或者它们是否仅具有部分功能。这些研究将有助于了解用于识别端粒丢失并指导细胞对端粒丢失的反应的机制。体细胞和生殖细胞之间的差异可以让我们深入了解人类细胞中发现的类似差异。