Retrotransposon virus-like particle assembly

逆转录转座子病毒样颗粒组装

• 批准号: 10241947
• 负责人: Sean Beckwith
• 金额: $ 6.86万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241947
• 关键词: Amino Acids; Antiviral Agents; Behavior; Biochemical; Biological; Biological Assay; Biology; Biophysical Process; Biophysics; Capsid; Capsid Proteins; Cells; Cellular biology; Chimera organism; Chimeric Proteins; Code; Communicable Diseases; Complementary DNA; Data; Dependence; Detergents; Disease; Drug Targeting; Electron Microscopy; Elements; Event; Evolution; Family; Fluorescence Microscopy; Fossils; Genes; Genetic; Genetic Transcription; Genome; Health; Human Genome; Immunoblotting; Influentials; Interruption; Investigation; Knowledge; Length; Life Cycle Stages; Liquid substance; Malignant Neoplasms; Measures; Mechanics; Medical; Microscopy; Mission; Modeling; Molecular; Mutate; National Institute of General Medical Sciences; Natural Immunity; Nerve Degeneration; Nuclear Import; Nucleic Acids; Phase; Phenotype; Play; Prion Diseases; Prions; Process; Property; Protein Sequence Analysis; Proteins; RNA; Research; Resistance; Retroelements; Retrotransposition; Retrotransposon; Retroviridae; Retrovirology; Reverse Transcription; Role; Saccharomyces cerevisiae; Shapes; Signal Transduction; Synapses; System; Testing; Therapeutic; Time; Virus; Virus-like particle; Work; Yeasts; expectation; fitness; gag Gene Products; information model; innovation; insight; mammalian genome; mutant; novel; prion hypothesis; prion-like; sup35; synaptic function; transposon/insertion element; yeast prion

PROJECT SUMMARY/ABSTRACT Retrotransposons and retroviruses shape genome evolution and impact host fitness. Over 40% of the human genome is comprised of mobile DNA elements. These elements, once considered dormant, molecular fossils, are in fact remarkably influential across a diverse array of medically-relevant processes. Retroelements and domesticated components of mobile elements play important roles in neurodegeneration, cancer, pluripotent cells, innate immunity, and synaptic signaling. The retrovirus-like transposon Ty1 is an informative model for understanding mechanisms employed by retrotransposons and retroviruses across their replication cycles. This proposal leverages the genetic, biochemical, and cell biological toolkit developed for studying Ty1 and combines innovative conceptual frameworks from retrovirology, biophysics, protein biology, and cell biology. The proposed project will identify parameters governing Ty1 Gag’s role in virus-like particle assembly. This will advance our understanding of retroelement replication cycles and establish mechanisms that may be utilized by other disease-relevant retrotransposons, retroviruses, and domesticated capsid genes. In addition, identification of novel mechanisms used by retroelements has the potential to define a new class of antiviral drug targets.

项目概要/摘要 逆转录转座子和逆转录病毒塑造基因组进化并影响宿主适应性。超过40%的人类 基因组由可移动的 DNA 元件组成。这些元素曾经被认为是休眠的分子化石， 事实上，在各种医学相关过程中都具有显着的影响力。复古元素和 移动元件的驯化成分在神经退行性变、癌症、多能性中发挥重要作用 细胞、先天免疫和突触信号传导。类逆转录病毒转座子 Ty1 是一个信息丰富的模型 了解逆转录转座子和逆转录病毒在其复制周期中采用的机制。这 该提案利用了为研究 Ty1 而开发的遗传、生化和细胞生物学工具包，并结合了 来自逆转录病毒学、生物物理学、蛋白质生物学和细胞生物学的创新概念框架。拟议的 该项目将确定控制 Ty1 Gag 在病毒样颗粒组装中的作用的参数。这将推进我们的 了解逆转录元件复制周期并建立可供其他人使用的机制 与疾病相关的逆转录转座子、逆转录病毒和驯化衣壳基因。此外，识别 逆转录元件使用的新机制有可能定义一类新的抗病毒药物靶点。