REGULATION OF GROWTH AND PROLIFERATION BY DROSOPHILA TOR

描述(申请者描述)：本项目的目标是 了解控制细胞生长和增殖的机制 发展。为此，我们建议对dtor进行遗传和分子研究。 果蝇酵母TOR和哺乳动物mTOR/FRAP蛋白激酶的同源物 它们在蛋白质合成和细胞周期调控中起着关键作用。这 该项目有四个主要目标。首先，确定Dtor活动的损失如何 结果在细胞周期停滞时，将使用FACS分析来确定细胞 需要数据驱动程序的周期阶段以及活动和级别 候选的细胞周期调节因子将在dtor突变背景下进行测量。 其次，我们将确定dtor向其两个 功能良好的靶标p70S6和4E-BP1。第三，我们将使用 基因和生化测试，以确定dtor活性是如何被调节的。我们 将区分两种可选假设：dtor是 P13K信号通路，并调节dtor活性以响应 营养水平。第四，这些候选分子的测试将是 辅以基因交互屏幕，旨在识别新的 DATOR的调节器和效应器。我们将筛选抑制基因突变 Dtor表型。TOR蛋白及其调节的生长途径是 在苍蝇和人类之间高度保守，因此我们预计这些 为人类发育过程中的生长控制提供洞察力的研究， 组织动态平衡和肿瘤发生。

DESCRIPTION (applicant's description): The goal of this project is to understand the mechanisms that govern cell growth and proliferation during development. To this end, we propose genetic and molecular studies of dTOR, a Drosophila homolog of the yeast TOR and mammalian mTOR/FRAP protein kinases which have crucial roles in protein synthesis and cell cycle regulation. This project has four major aims. First, to determine how loss of dTOR activity results in cell cycle arrest, FACS analysis will be used to determine the cell cycle phases in which dTOR is required, and the activity and levels of candidate cell cycle regulators will be measured in dTOR mutant backgrounds. Second, we will determine the mechanisms by which dTOR signals to two of its well characterized targets, p70 S6 kinase and 4E-BP1. Third, we will use genetic and biochemical tests to determine how dTOR activity is regulated. We will distinguish between two alternative hypothesis: that dTOR is a target of the P13K signaling pathway, and that dTOR activity is regulated in response to nutrient levels. Fourth, these tests of candidate molecules will be complemented by genetic interaction screens aimed at identifying novel regulators and effectors of dTOR. We will screen for mutations that suppress dTOR phenotypes. The TOR protein and the growth pathways it regulates are highly conserved between flies and humans, and therefore we expect these studies to provide insights into growth control during human development, tissue homeostasis, and tumorigenesis.