RUI: Arginine methylation of a lipin homologue and its function in phospholipid biosynthesis in Trypanosoma brucei

RUI：脂质同源物的精氨酸甲基化及其在布氏锥虫磷脂生物合成中的功能

• 批准号: 1614521
• 负责人: Michel Pelletier
• 金额: $ 36.64万
• 依托单位: SUNY College at Brockport
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1614521&HistoricalAwards=false
• 关键词: RUI; Arginine; methylation; lipin; homologue

RUI: Arginine methylation of a lipin homologue and its function in phospholipid biosynthesis in Trypanosoma bruceiThe research question focuses on investigating modifications of a novel protein involved in essential phospholipid biosynthesis in the parasitic protozoan Trypanosoma brucei. T. brucei spends part of its life cycle in the human bloodstream and part in the African tsetse fly, thus presenting an interesting model system for studies of parasitic adaptation to multiple eukaryotic hosts. This project will strengthen the research environment in the Department of Biology at The College at Brockport, SUNY, by providing opportunities for undergraduate and Master's level graduate students to participate directly in hypothesis driven basic research using an important protozoan model system. In addition, the independent undergraduate research projects will expose participants to science in an interactive, collaborative, constructive framework. Involvement in high impact research activities will enhance the overall educational experience and increase student ability to secure graduate positions, admission to professional school, and employment in various biological disciplines.The major objective of this project is to identify the function(s) of TbLpn, a recently identified protein, and its importance in trypanosome metabolism using a dual genetic/biochemical approach. The functions of TbLpn and the effect of arginine methylation will be assessed in vivo by disrupting its expression by RNA interference and determining the effect of the disruption on cellular growth, cell morphology, cellular phospholipid content, phosphatidic acid phosphatase activity, and expression of lipid biosynthetic genes. This research will address important aspects of trypanosome biology and will constitute an area for growth in the fields of both parasitology and protein modification. By using an innovative approach, potential roles of a novel protein in phospholipid biosynthesis and virulence will be unveiled. In addition, it will potentially increase our understanding of protein arginine methylation in an evolutionarily ancient parasite, and provide insight into the mechanisms and evolution of this common posttranslational modification in higher organisms.

- 我知道精氨酸甲基化的脂蛋白同系物和其功能的磷脂生物合成中的布氏锥虫的研究问题的重点是调查一种新的蛋白质的修饰参与必需的磷脂生物合成中的寄生原生动物布氏锥虫。T.布氏杆菌的部分生命周期在人类血液中度过，部分在非洲采采蝇中度过，从而为研究寄生虫对多种真核宿主的适应性提供了一个有趣的模型系统。该项目将加强在纽约州立大学Brockport学院生物系的研究环境，为本科生和硕士研究生提供机会，直接参与假设驱动的基础研究，使用一个重要的原生动物模型系统。此外，独立的本科生研究项目将使参与者在互动，协作，建设性的框架中接触科学。参与高影响力的研究活动将提高整体的教育经验，提高学生的能力，以确保研究生职位，进入专业学校，并在各种生物学科就业。本项目的主要目标是确定的功能（S）的TbLpn，最近发现的蛋白质，其在锥虫代谢中的重要性，使用双重遗传/生化方法。TbLpn的功能和精氨酸甲基化的影响将在体内通过RNA干扰破坏其表达并确定破坏对细胞生长、细胞形态、细胞磷脂含量、磷脂酸磷酸酶活性和脂质生物合成基因表达的影响来评估。这项研究将解决锥虫生物学的重要方面，并将构成寄生虫学和蛋白质修饰领域的增长领域。通过使用创新的方法，一种新的蛋白质在磷脂生物合成和毒力中的潜在作用将被揭示。此外，它将潜在地增加我们对进化上古老的寄生虫中的蛋白质精氨酸甲基化的理解，并提供对高等生物中这种常见的翻译后修饰的机制和进化的见解。