Understanding Complex Genome Editing and RNA Biology in Oxytricha

项目概要 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，带来了强大的分子和 理解基因组进化和多样性的机械方法。令人惊讶的复杂 微生物真核生物中 DNA 和 RNA 加工的变异显示出广泛的基因组结构 和遗传系统。一些途径侵蚀了基因的概念（例如乱序基因和 RNA 编辑） 甚至孟德尔遗传，提醒我们基因组序列草案可能与知识相去甚远 其产品。基因组重排发生在多种生物体中，并导致许多人类疾病， 尤其是癌症——一种基因组疾病，但程序性 DNA 重排的程度极高 纤毛虫尖毛虫发育所需的基因使其成为研究基因组重塑的理想模型系统 以及 RNA 在协调这一过程中的作用。拟议的研究将扩大实验室的重点 这种非凡自然现象的分子机制和进化。未来五年的目标 包括了解 DNA N6-腺嘌呤甲基化 (6mA) 在发育过程中的作用以及 重排，以及小和长非编码 RNA 及其相关 RNA 之间的相互作用 结合蛋白，以及重新排列的基因组。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深入了解 乱序基因组和复杂遗传结构的进化起源，解决了基本问题 开发过程中如何执行程序重排以及这个过程是如何产生的问题 在进化过程中。

Project Summary 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.