Retrotransposon virus-like particle assembly

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 基因组由移动的DNA元件组成。这些曾经被认为是休眠的分子化石， 事实上，它们对各种医学相关过程都有着显著的影响。Retroelements和 移动的元件的驯化组分在神经变性、癌症、多能性神经退行性疾病、神经退行性疾病和神经退行性疾病中起重要作用。 细胞、先天免疫和突触信号传导。逆转录病毒样转座子Ty 1是一个信息模型， 理解逆转录转座子和逆转录病毒在其复制周期中所采用的机制。这 该提案利用了为研究Ty 1而开发的遗传、生物化学和细胞生物学工具包， 从逆转录病毒学，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 该项目将确定控制Ty 1 Gag在病毒样颗粒组装中作用的参数。这将推动我们的 了解retroelement复制周期，并建立可被其他人利用的机制。 疾病相关逆转录转座子、逆转录病毒和驯化衣壳基因。此外，识别 逆转录分子使用的新机制有可能定义一类新的抗病毒药物靶点。

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.