Understanding the chromatin remodeling factor kismet in glutamatergic neuron development and function

适当的基因表达调控对于神经系统的正常发育和功能至关重要。染色质重塑，或DNA结构的改变，是基因调控的关键步骤，是神经系统发育和功能的重要过程。在哺乳动物中，氨基酸谷氨酸介导了神经系统中的大部分信号，并调节了学习、记忆和神经退化的基础过程。控制谷氨酸能神经元(使用谷氨酸的神经元)的发育和功能的因素是相当广泛的兴趣。然而，这些因素在很大程度上是未知的。本项目的目的是为了更好地了解染色质重塑蛋白Kismet在谷氨酸能神经元发育和功能中的功能。这项提议将利用遗传学和分子生物学来实现这一目标。该项目将确定哪些信号激活Kismet，随后Kismet激活谷氨酸能神经元中的哪些基因来调节其功能。这个项目的影响是多方面的。首先，虽然这些研究是针对谷氨酸能神经元中Kismet功能的，但这项研究的结果将有助于我们了解染色质重塑因子如何调节其他细胞的功能。其次，该项目将为本科生提供在马伦达实验室进行定向研究的机会。第三，该奖项将支持本科生的混合班，这将解决多所大学的一个重要问题：容纳大量希望参与本科生研究但由于师生比例有限而无法参与的本科生。重要的是，这个混合班级的结果是通过课前和课后调查来评估的。因此，这个项目不仅解决了神经发展中的重要问题，也解决了科学教育和培训中的重要问题。

The proper regulation of gene expression is critical for the normal development and function of the nervous system. "Chromatin remodeling", or the alteration of DNA structure, is a key step in gene regulation and is an important process in nervous system development and function. In mammals, the amino acid glutamate mediates the majority of signaling in the nervous system, and regulates processes that underlie learning, memory, and neurodegeneration. Factors that control the development and function of glutamatergic neurons (neurons that use glutamate) are of considerable and broad interest. Yet, these factors are largely unknown. The objective of this project is to better understand the function of the chromatin remodeling protein Kismet in the development and function of glutamatergic neurons. This proposal will utilize both genetics and molecular biology to accomplish this goal. This project will determine which signals activate Kismet, and subsequently, which genes Kismet activates in glutamatergic neurons to regulate their function. The broader impacts of this project are manifold. First, though these studies are particular to Kismet function in glutamatergic neurons, the results from this research will help us understand how chromatin remodeling factors regulate the function of other cells as well. Second, this project will provide research opportunities for undergraduate students to perform directed research in the Marenda laboratory. Third, this award will support a hybrid class for undergraduate students that will addresses a significant problem in multiple universities: accommodating the large number of undergraduate students who want to participate in undergraduate research, but can not due to limited faculty to student ratios. Importantly, the outcome of this hybrid class is assessed through pre- and post-class surveys. Therefore, this project not only addresses important questions in neural development, but also addresses important concerns in science education and training.