Identification and study of adaptive mutations and phenotypes using laboratory growth of C. elegans

项目概要/摘要 进化的力量对人类疾病的发展，社会行为， 和代谢沿着癌症的进展和对病原体的易感性。这些力 在很大程度上决定了影响或构成这些特征的遗传变化和基因的类型。的 麦格拉思实验室的目标是了解适应的遗传基础。基因的变化是什么 以及它们如何改变细胞活性和表型变化来实现 这个吗？利用模式生物C. elegans是一个强大的方法来解决 这些问题。C.线虫，一种遗传上易驾驭的短命线虫，可以用来研究 发育、行为和有性生殖的进化。在接下来的五年里，麦格拉思实验室 将继续确定适应的遗传、细胞和表型基础，重点是 三个主要领域。首先，信息素依赖的性状进化的遗传和细胞基础将是 表征了C.秀丽线虫释放和感觉数十种螨糖苷信息素， 行为和发展特征的数量。这项工作将提供一个模型，了解如何 神经回路进化以在新环境中修改信息素信号。第二，功能性 将在一些线虫中表征BMPF染色质重塑复合物的进化 物种染色质状态调节基因表达;它对于决定细胞命运和 表型可塑性染色质重塑的基因突变是许多癌症的重要风险因素。 癌的最后，将确定负责食物消耗差异的基因和神经元。 肥胖是美国人常见的危险因素。在C. elegans可以帮助我们设计 减少人类肥胖的方法。总之，这项工作将提供一个适应的看法， 多细胞生物

Project Summary/Abstract Evolutionary forces have important consequences for human diseases of development, social behavior, and metabolism along with the progression of cancers and susceptibility to pathogens. These forces largely determine the types of genetic changes and genes that influence or underlie these traits. The goal of the McGrath lab is to understand the genetic basis of adaptation. What are the genetic changes that can increase fitness and how do they modify cellular activity and phenotypic change to accomplish this? Experimental evolution using the model organism C. elegans is a powerful approach to address these questions. C. elegans, a genetically-tractable, short-lived nematode, can be used to study the evolution of development, behavior, and sexual reproduction. In the next five years, the McGrath lab will identify continue to identify the genetic, cellular, and phenotypic basis of adaptation, focusing on three main areas. First, the genetic and cellular basis of pheromone-dependent trait evolution will be characterized. C. elegans release and sense dozens of acaroside pheromones that modify a large number of behavioral and developmental traits. This work will provide a model for understanding how neural circuits evolve to modify pheromone signaling in new environments. Second, the functional evolution of the NURF chromatin remodeling complex will be characterized in a number of nematode species. Chromatin state regulates gene expression; it is important for determining cell fate and phenotypic plasticity. Genetic mutations in chromatin remodelers are an important risk factor for many cancers. Finally, genes and neurons responsible for differences in food consumption will be identified. Obesity is a common risk factor in Americans. Fundamental work in C. elegans could help us design approaches to decrease obesity in humans. In total, this work will provide a view of adaptation in a multicellular organism.