The genetics of the Drosophila IIS pathway response to changing nutrition

果蝇 IIS 途径对营养变化反应的遗传学

基本信息

批准号：
8460695
负责人：
Elizabeth Griep King
金额：
$ 4.11万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-02 至 2014-01-01
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Modern human populations have experienced changes in diet and activity levels, leading to an increase in metabolic disorders. The IIS pathway is known to influence many aspects of growth, metabolism, and longevity but little is known about the genetic basis of standing variation in the pathway. The goal of this project is to examine the genetic basis of natural genetic variation in the insulin/insulin-like signaling (IIS) pathway. The project will utilize a newly developed resource for the genetic analysis of complex traits, the Drosophila Synthetic Population Resource (DSPR). Gene expression levels for every gene in the IIS pathway will be measured in three different nutritional conditions and QTL influencing these gene expression levels will be mapped. The project will identify the source of natural genetic variation in IIS and determine if genetic variants co-localize with the genes encoding major proteins in the pathway. Genes influencing gene expression will be identified in multiple nutritional environments, making it possible to determine if the same or different variants control the IIS pathway in different environments. In addition, the project will address whether the same "master genes" control several components of the IIS pathway. The project will also answer broad questions about the nature of the interactions between components of the IIS pathway using systems biology approaches. By using the DSPR, this project will be able to map QTL influencing the IIS pathway to 1-2 centiMorgans, estimate both the effect and frequency of those QTL and identify potentially causative sites. The IIS pathway is highly conserved between Drosophila melanogaster and humans and therefore, identifying the genes controlling IIS signaling in Drosophila may directly identify targets for pharmacological intervention, particularly if "master genes" are identified. Ultimately, this project will characteize the genetic basis of a central endocrine pathway that has direct implications for our understanding of metabolism and the internal allocation of resources.

描述（由申请人提供）：现代人类经历了饮食和活动水平的变化，导致代谢紊乱的增加。众所周知，IIS 途径会影响生长、代谢和寿命的许多方面，但对该途径中持续变异的遗传基础知之甚少。该项目的目标是检查胰岛素/胰岛素样信号传导 (IIS) 途径中自然遗传变异的遗传基础。该项目将利用新开发的资源进行复杂性状的遗传分析，即果蝇综合种群资源（DSPR）。将在三种不同的营养条件下测量 IIS 途径中每个基因的基因表达水平，并绘制影响这些基因表达水平的 QTL。该项目将确定 IIS 中自然遗传变异的来源，并确定遗传变异是否与编码该通路中主要蛋白质的基因共定位。将在多种营养环境中鉴定影响基因表达的基因，从而可以确定相同或不同的变体在不同环境中控制 IIS 途径。此外，该项目还将解决是否相同的“主基因”控制 IIS 通路的多个组件。该项目还将利用系统生物学方法回答有关 IIS 通路各组成部分之间相互作用的性质的广泛问题。通过使用 DSPR，该项目将能够将影响 IIS 途径的 QTL 定位到 1-2 centiMorgans，估计这些 QTL 的效果和频率，并识别潜在的致病位点。 IIS 通路在果蝇和人类之间高度保守，因此，鉴定果蝇中控制 IIS 信号传导的基因可以直接确定药理干预的靶标，特别是在鉴定出“主基因”的情况下。最终，该项目将描述中央内分泌途径的遗传基础，这对我们对新陈代谢和资源内部分配的理解具有直接影响。