CAREER: Investigating Epithelial Tube-Size Control Mechanisms Using the Drosophila Tracheal System

职业：利用果蝇气管系统研究上皮管尺寸控制机制

• 批准号: 0133411
• 负责人: Greg Beitel
• 金额: $ 63.26万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-15 至 2006-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0133411&HistoricalAwards=false
• 关键词: CAREER; Investigating; Epithelial; Tube; Size

The proposal outlines an integrated plan of teaching and research that will provide a solid foundation for the awardee's future contributions to education and science. The first undergraduate educational aims are to develop the awardee's teaching skills and to improve the current undergraduate cell biology course using the resources of Northwestern University's Searle Center for Teaching Excellence. The second undergraduate educational aim is to provide undergraduate research opportunities by having some of the proposed research aims performed by summer undergraduate researchers. The graduate education aims include organizing a new developmental genetics course and a new presentation series. The proposed research focuses on understanding the mechanisms underlying morphogenesis of epithelial and endothelial tubes. Despite the importance of correct tube diameter and length to the function of organs such as the vascular system, lung and kidney, there is little understanding of the complex cytoskeletal and extracellular matrix changes, dynamic rearrangement of cell-cell junctions, or coordinated cell shape changes that create tubes of particular sizes. To identify and study the functions of genes required for tube-size control, the proposed research will use molecular/genetic approaches to investigate morphogenesis of the Drosophila tracheal system, a ramifying network of epithelial tubes that functions as a combined pulmonary/vascular system. Previously, mutations in a group of eight genes that specifically control tracheal tube size have been identified. It has now been determined that one of these genes encodes a b-subunit of a Na+ K+ ATPase transporter and that mutations in the Na+ K+ ATPase a-subunit a-ATPase(93A) cause similar tracheal tube-size defects. Preliminary data suggests that the Na+ K+ ATPase is required to organize tracheal cell junctions, a novel role for a Na+ K+ ATPase. To better understand the mechanisms of epithelial tube-size control and the roles of the Na+ K+ ATPase, the genetic and cell biological functions of a-ATPase(93A) during tracheal tube morphogenesis will be investigated. In addition, the tracheal tube-size control gene varicose that genetic epistasis experiments suggest acts in parallel to the Na+ K+ ATPase will be cloned and characterized. Together, the analyses of a-ATPase(93A)and varicose will improve the understanding of the basic cell biological and molecular mechanisms of epithelial and endothelial tube-size control.

该提案概述了教学和研究的综合计划，将为获奖者未来对教育和科学的贡献提供坚实的基础。第一个本科教育目标是发展获奖者的教学技能，并利用西北大学Searle卓越教学中心的资源改进现有的本科细胞生物学课程。第二个本科教育目标是通过让暑期本科生研究人员执行一些拟议的研究目标来提供本科生研究机会。研究生教育的目标包括组织一门新的发育遗传学课程和一系列新的演讲。拟议的研究集中在了解上皮和内皮管形态发生的潜在机制。尽管正确的管径和长度对血管系统、肺和肾脏等器官的功能很重要，但人们对复杂的细胞骨架和细胞外基质的变化、细胞-细胞连接的动态重排或产生特定大小的管的协调细胞形状变化知之甚少。为了识别和研究控制管子大小所需的基因的功能，拟议的研究将使用分子/遗传学方法来研究果蝇气管系统的形态发生，果蝇气管系统是一种由上皮管组成的分支网络，起着联合肺/血管系统的作用。此前，已发现一组8个基因的突变，这些基因专门控制气管导管的大小。现在已经确定，其中一个基因编码Na+K+ATPase转运体的b亚基，Na+K+ATPase a亚基(93A)的突变会导致类似的气管大小缺陷。初步数据表明，Na+K+ATPase是组织气管细胞连接所必需的，这是Na+K+ATPase的一个新的作用。为了更好地了解上皮管大小控制的机制和Na+K+ATPase的作用，我们将对α-ATPase(93A)在气管形态发生中的遗传和细胞生物学功能进行研究。此外，遗传上位性实验表明与Na+K+ATPase平行作用的气管管径控制基因静脉曲张将被克隆和鉴定。总之，对α-ATPase(93A)和静脉曲张的分析将提高对上皮和内皮细胞管径控制的基本细胞生物学和分子机制的理解。