RUI: Role of Germ Cell Nanoparticles during Germline Specification in Drosophila

RUI：生殖细胞纳米颗粒在果蝇种系规范中的作用

• 批准号: 1715541
• 负责人: Alexey Arkov
• 金额: $ 69.53万
• 依托单位: Murray State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1715541&HistoricalAwards=false
• 关键词: RUI; Role; Germ; Cell; Nanoparticles

This project focuses on the biological functions and assembly of germ cell nanoparticles. These are small molecular structures that may hold a key to unexplained fundamental aspect of germline, namely its unique ability to give rise to the next-generation individuals and therefore, ensure the continuity of life. Germ cells belong to a special class of cells that produce egg and sperm which unite to generate a completely new organism. Germ cell nanoparticles have been remarkably conserved across animal phyla indicating their crucial biological importance. In addition, this research may promote design of artificial nanoparticles with desired molecular characteristics thereby leading to technological breakthroughs. This project will involve undergraduate, graduate students and a postdoctoral scholar and will provide opportunities for training of future active participants in science and education fields. In addition, the research topics will be incorporated into genetics courses and a new cell biology laboratory module will be designed. This research will be described on the University National Public Radio providing a great platform to reach out to the general public.This project aims to understand the principles of the functional assembly of germ cell molecular complexes composed of RNA and proteins required for germline development in diverse organisms. Components of these complexes include Tudor domain-containing proteins, Piwi proteins, small Piwi-interacting RNAs (piRNAs) and enzymes of the glycolytic cluster. These complexes play a major role in the silencing of transposable elements, which otherwise might lead to harmful mutations. However, the mechanisms controlling their assembly remains a mystery. To address this gap, a combination of approaches--including genetics, biochemistry, as well as in vitro and in vivo experiments--will be used to test the roles of the component proteins in assembly of these germ cell particles in Drosophila. Because these structures have been evolutionarily conserved, this research can serve as a paradigm for studying other large and dynamic ribonucleoprotein granules. Moreover, the results have the potential to reveal new insights into how such nanoparticles function to preserve the integrity of the next generation genetic material.

本项目主要研究生殖细胞纳米粒子的生物学功能和组装。这些小分子结构可能是生殖系无法解释的基本方面的关键，即其产生下一代个体的独特能力，从而确保生命的连续性。生殖细胞属于一类特殊的细胞，它们产生卵子和精子，卵子和精子结合在一起产生一个全新的生物体。生殖细胞纳米颗粒在动物门中非常保守，这表明它们具有重要的生物学意义。此外，这项研究可能促进具有所需分子特征的人工纳米颗粒的设计，从而导致技术突破。该项目将涉及本科生、研究生和一名博士后学者，并将为培训未来科学和教育领域的积极参与者提供机会。此外，研究课题将纳入遗传学课程，并将设计一个新的细胞生物学实验室模块。该研究将在大学国家公共广播电台上进行介绍，为广大公众提供一个很好的平台。本项目旨在了解由RNA和蛋白质组成的生殖细胞分子复合物的功能组装原理，这些复合物是各种生物体中生殖细胞发育所需的。这些复合物的组分包括含Tudor结构域的蛋白质、Piwi蛋白、小Piwi相互作用RNA（piRNA）和糖酵解簇的酶。这些复合物在转座因子的沉默中起主要作用，否则可能导致有害的突变。然而，控制它们组装的机制仍然是一个谜。为了解决这一差距，将使用多种方法-包括遗传学，生物化学以及体外和体内实验-来测试组成蛋白在果蝇中组装这些生殖细胞颗粒中的作用。 由于这些结构在进化上是保守的，因此这项研究可以作为研究其他大型动态核糖核蛋白颗粒的范例。 此外，这些结果有可能揭示这种纳米颗粒如何发挥作用以保持下一代遗传物质的完整性的新见解。

项目成果

Protein components of ribonucleoprotein granules from Drosophila germ cells oligomerize and show distinct spatial organization during germline development

• DOI: 10.1038/s41598-019-55747-x
• 发表时间: 2019-12
• 期刊: Scientific Reports
• 影响因子: 4.6
• 作者: Hieu D. L. Vo;Wahiduzzaman;Samuel J. Tindell;Jimiao Zheng;Ming Gao;A. Arkov