Understanding Complex Genome Editing and RNA Biology in Oxytricha

了解棘毛虫的复杂基因组编辑和RNA生物学 项目摘要/摘要： PI的实验室研究微生物真核生物中的自然基因组编辑系统，带来了强有力的 了解基因组进化和多样性的分子和机制方法。令人惊讶的是 微生物真核生物DNA和RNA加工的复杂变异显示了广泛的基因组 建筑和遗传系统。一些途径侵蚀了基因的概念(例如，打乱的基因和 RNA编辑)，甚至孟德尔式的遗传，提醒我们，一个草稿的基因组序列可能是相去甚远的 来自对其产品的了解。基因组重排发生在不同的生物体中，并对许多 人类疾病，尤其是癌症--一种基因组疾病，但编程DNA的极端水平 纤毛虫Oxytricha发育所需的重排使其成为研究的理想模式系统 基因组重塑和RNA在协调这一过程中的作用。拟议中的研究将扩大 该实验室的重点是这一非凡自然现象的分子机制和进化。目标为 接下来的五年包括了解DNA N6-腺嘌呤甲基化(6 MA)在发育过程中的作用 和重排，以及小的和长的非编码RNA与其相关的RNA之间的相互作用- 结合蛋白，以及重排的基因组。来自分子遗传学、生物化学和 染色质生物学为功能研究提供了平台，而比较基因组学则提供了对 杂乱基因组和复杂遗传结构的进化起源，解决了 在开发过程中如何执行程序化重新安排以及如何执行这些基本问题 这一过程发生在进化过程中。

Understanding Complex Genome Editing and RNA Biology in Oxytricha Project Summary/Abstract: The PI’s lab studies natural genome editing systems in microbial eukaryotes, bringing a strongly molecular and mechanistic approach to understanding genome evolution and diversity. The surprisingly sophisticated variations on DNA and RNA processing in microbial eukaryotes display a wide range of genome architectures and genetic systems. Some pathways erode the notions of a gene (e.g. scrambled genes and RNA editing) and even Mendelian inheritance, reminding us that a draft genome sequence can be a far cry from knowledge of its products. Genome rearrangements occur in diverse organisms, and contribute to many human diseases, especially cancer—a disease of the genome, but the extreme level of programmed DNA rearrangements required for development in the ciliate Oxytricha make it an ideal model system to study genome remodeling and the roles of RNA in orchestrating this process. The proposed research will expand the lab’s focus on the molecular mechanisms and evolution of this remarkable natural phenomenon. Goals for the next five years include understanding the roles of DNA N6-adenine methylation (6mA) during development and rearrangement, and the interactions between small and long noncoding RNAs and their associated RNA- binding proteins, together with the rearranging genome. Tools from molecular genetics, biochemistry, and chromatin biology provide the platform for functional studies, while comparative genomics offers insight into the evolutionary origins of scrambled genomes and complex genetic architectures, addressing the fundamental questions of how programmed rearrangements are executed during development and how this process arose during evolution.