Understanding Complex Genome Editing and RNA Biology in Oxytricha

了解尖毛虫中复杂的基因组编辑和 RNA 生物学

• 批准号: 10415638
• 负责人: LAURA F LANDWEBER
• 金额: $ 77.17万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10415638
• 关键词: Address; Adenine; Architecture; Biochemistry; Biological Models; Biology; Chromatin; Chromosomal Rearrangement; Complex; DNA; Development; Disease; Eukaryota; Event; Evolution; Frequencies; Functional disorder; Gene Rearrangement; Genes; Genetic; Genome; Genome Stability; Genomic Instability; Goals; Human; Inherited; Knowledge; Maintenance; Malignant Neoplasms; Methylation; Molecular; Molecular Genetics; Organism; Oxytricha; Pathway interactions; Process; Public Health; RNA; RNA Editing; RNA Processing; RNA-Binding Proteins; Research; Role; System; Tumor Suppressor Genes; Untranslated RNA; Variant; chimeric gene; comparative genomics; genetic architecture; genome editing; genome integrity; human disease; insight; microbial; overexpression; tool; tumor

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.

了解毛霉的复杂基因组编辑和RNA生物学