DISSERTATION RESEARCH: Determining the functional genetic basis of natural variation in thermosensory behavior

人们知道行为会受到个体间自然遗传变异的影响，但人们对这种变异导致行为改变的确切生理机制知之甚少。这个问题的解决方案既取决于识别负责行为反应自然变异的基因，也取决于理解这些基因如何影响神经功能的生理学。秀丽隐杆线虫是一种自由生活的土壤线虫，是研究自然变异对行为影响的理想生物。 它有一个相对简单的神经系统和一个完整的注释测序基因组，该物种的野生分离株显示出极其不同的温度偏好。这项研究将使用遗传杂交来绘制和克隆负责行为自然变异的基因。然后，微流体设备将用于创建精确的温度选择环境，允许使用单个神经元的钙成像来分析这些差异的生理基础。这项工作通过跨学科的研究生培训，本科生参与研究，以及通过校园教育网络面向社区的科学教育产生了更广泛的影响。这将是第一批确定多个基因中特定变化的研究之一，这些基因共同作用，导致复杂行为的生理机制发生变化。这些联系对于开始理解自然界以及人类群体中行为反应的巨大多样性是必要的。

Behavior is known to be influenced by natural genetic variation among individuals, yet the precise physiological mechanisms that alter behavior as a result of this variation are poorly understood. The solution to this problem depends both on identifying genes responsible for natural variation in behavioral responses and on understanding the physiology of how those genes affect neural function. Caenorhabditis elegans, a free-living soil-dwelling nematode, is an ideal organism to address the effects of natural variation on behavior. It has a relatively simple nervous system and a fully annotated sequenced genome, and wild isolates of this species show extremely different temperature preferences. This study will use genetic crosses to map and clone the genes responsible for natural variation in behavior. Microfluidic devices will then be used to create a precise temperature choice environment, allowing the physiological basis of these differences to be analyzed using calcium imaging of individual neurons. This work has broader impacts via interdisciplinary graduate training, involvement of undergraduates in research, and community-oriented scientific education through a Campus Educational Network. This will be among the first studies to identify specific changes in multiple genes that work together to cause variation in the physiological mechanisms of a complex behavior. These connections are necessary to begin to understand the vast diversity of behavioral responses within the natural world, as well as within human populations.