Understanding Complex Gene Editing Systems and RNA Biology in Oxytricha

了解棘豆属复杂的基因编辑系统和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新遗传系统，带来了强大的分子和 理解基因组进化和多样性的机械论方法。令人惊讶的老练 微生物真核生物DNA和RNA加工的变异表现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，打乱的基因和RNA编辑) 甚至是孟德尔式的遗传，提醒我们基因组序列可能远远不同于 它的产品。基因组重排发生在不同的生物体中，并导致许多人类疾病， 尤其是癌症--一种基因组疾病，但极高水平的程序化DNA重排和 纤毛虫对染色体重排的正确发育使其成为一种 研究基因组重塑和RNA在这一过程的表观遗传控制中的作用的理想模型系统。 拟议的研究将侧重于了解这一现象的分子机制和进化起源。 值得注意的现象。未来五年的目标包括更详细地了解 小的和长的非编码RNA之间的相互作用，既相互作用，也与 重新排列基因组。来自分子遗传学、RNA生物化学和染色质生物学的工具提供了 功能研究的平台，而近亲和远亲物种的比较基因组学将 提供对杂乱基因组和复杂遗传结构的进化起源的洞察 Oxytricha谱系，解决了它们在发育过程中如何重新排列以及它们如何 是在进化过程中产生的。

Understanding Complex Gene Editing Systems and RNA Biology in Oxytricha Project Summary/Abstract: The PI's lab studies novel genetic 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 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 and dependence on chromosomal rearrangements for correct development in the ciliate Oxytricha make it an ideal model system to study genome remodeling and the roles of RNA in epigenetic control of this process. The proposed research will focus on understanding the molecular mechanism and evolutionary origin of this remarkable phenomenon. Goals for the next five years include obtaining a more detailed understanding of the interactions between small and long noncoding RNAs, both with each other and together with the rearranging genome. Tools from molecular genetics, RNA biochemistry, and chromatin biology provide the platform for functional studies, while comparative genomics of closely and more distantly related species will provide insight into the evolutionary origins of scrambled genomes and complex genetic architectures in the Oxytricha lineage, addressing the basic questions of how they rearrange during development and how they arose during evolution.