RUI: Genetic Analysis of Gurken translational Control in Drosophila

RUI：果蝇 Gurken 翻译控制的遗传分析

• 批准号: 1243951
• 负责人: Scott Ferguson
• 金额: $ 25.07万
• 依托单位: SUNY College at Fredonia
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1243951&HistoricalAwards=false
• 关键词: RUI; Genetic; Analysis; Gurken; translational

Intellectual merit: All animals must reproducibly establish their body plan in the face of a constantly changing environment. Gurken is an evolutionarily conserved growth factor that is carefully regulated to establish the anterior / posterior and dorsal / ventral axis during oogenesis in the fruit fly Drosophila melanogaster. This project aims to identify the mechanisms by which the translation of Gurken is regulated by addressing the response of gurken mRNA to two stimuli: Nutrient limitation and DNA-damage. The first goal of the research is to understand how Drosophila maintain robust developmental patterning when confronted with an environment where the availability of nutrients is highly variable. The production of proteins is highly regulated in response to nutrient availability and ensures the efficient utilization of resources. Translation in the cell is globally repressed when nutrients are scarce; however, a small subset of essential proteins escape this repression by employing an alternative mechanism known as IRES-mediated translation. Preliminary work from the PI's lab suggests that the gurken mRNA utilizes this alternative mechanism to maintain the axis patterning when nutrients are limiting. The research will utilize a number of genetic and biochemical approaches to study the activity of the gurken mRNA both in vitro and in vivo. Specifically, the activity of regulatory regions of the gurken mRNA will be probed by joining them to light emitting luciferase reporter genes. This will facilitate the discovery of IRES elements that allow the oocyte to maintain its robust patterning. The second goal of the research is to understand how damage to the genome that occurs during meiosis affects the translation of gurken. Previous research has shown that mutations that interfere with DNA repair inhibit the translation of gurken by an unknown mechanism. Several novel mutations that affect this signaling pathway have been isolated. This project will take a genomic sequencing approach to identify these mutations and shed light on the mechanism(s) that communicates the integrity of the genome to developmental patterning molecules.Broader Impact: The research conducted in this project will engage students in the study of translation regulation at the State University of New York College at Fredonia, a predominantly undergraduate institution. The research will address several pressing questions in the field, as indicated above, while allowing students to be the driving force behind the activities. The students will be intimately involved in the design and execution of the experiments and have the opportunity to present the results of the project at regional and national meetings. The research will directly impact not only the students working in the PI's laboratory, but also students that are enrolled in the core genetics lab and upper level molecular genetics lab courses (approximately 70 students per year). The project will facilitate full-time research experiences for three summer students that will be recruited from Fredonia and/or regional community colleges.

知识分子的优点：面对不断变化的环境，所有动物都必须可重复地制定身体计划。古肯（Gurken）是一种进化保守的生长因子，在果蝇果蝇果蝇中，仔细调节了在卵子发生过程中建立前 /后 /腹侧 /腹侧轴。该项目旨在通过解决Gurken mRNA对两个刺激的反应来调节古尔肯的翻译的机制：营养限制和DNA损伤。该研究的第一个目标是了解果蝇面对营养物质可用性高度可变的环境时如何保持强大的发育模式。蛋白质的生产受到养分可用性的高度调节，并确保资源有效利用。当营养稀缺时，细胞中的翻译被全局抑制。但是，一小部分必需蛋白质通过采用一种称为IRES介导的翻译的替代机制来避免这种抑制。 PI实验室的初步工作表明，Gurken mRNA利用这种替代机制在限制营养时保持轴形成图案。该研究将利用许多遗传和生化方法在体外和体内研究Gurken mRNA的活性。具体而言，将探测Gurken mRNA的调节区域的活性，通过将它们加入发射荧光素酶报告基因的光。这将有助于发现IRES元素，这些元素使卵母细胞能够保持其强大的图案。该研究的第二个目标是了解减数分裂过程中发生的基因组的损害如何影响古尔肯的翻译。先前的研究表明，干扰DNA修复的突变通过未知机制抑制了古尔肯的翻译。几种影响这种信号通路的新型突变已被隔离。该项目将采用一种基因组测序方法来识别这些突变，并阐明了传达基因组对发展模式分子完整性的机制。BRODER的影响：该项目进行的研究将吸引学生研究纽约大学弗雷多尼亚州立大学弗雷多尼亚大学弗雷多尼亚大学的翻译调节研究，主要是不足的培训。如上所述，该研究将解决该领域的几个紧迫问题，同时允许学生成为活动背后的动力。学生将密切参与实验的设计和执行，并有机会在区域和国家会议上介绍该项目的结果。这项研究不仅会直接影响在PI实验室工作的学生，而且还会影响参加核心遗传学实验室和上层分子遗传学实验室课程的学生（每年约70名学生）。该项目将促进三名夏季学生的全日制研究经验，这些研究将从弗雷多尼亚和/或地区社区学院招募。