MOLECULAR GENETICS OF LEISHMANIA VIRULENCE

利什曼原虫毒力的分子遗传学

• 批准号: 2059475
• 负责人: YIXIN WANG
• 金额: $ 2.37万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-01-31 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2059475
• 关键词: MOLECULAR; GENETICS; LEISHMANIA; VIRULENCE

Leishmania species have emerged as excellent model systems for the study of molecular genetics of infectious diseases, in addition to their importance as human pathogens. I am going to employ the genetic approach of functional complementation to study the virulence properties of Leishmania. The success of this strategy has been demonstrated by the complementation of several mutant lines of L. donovani lacking lipophosphoglycan (LPG) a cell-surface virulence determinant. I plan to use this method to select for restoration of virulence properties other than LPG expression. I will infect BALB/c mice with a pool of avirulent L. major parasites that have been transfected with a cosmid library from a virulent strain of the parasite. Only those parasites with restored virulence will be allowed to resist the mouse's defense and form a lesion, from which they can be recovered for genetic and molecular analysis. Using this approach, l will pursue gene(s) responsible for enhanced virulence. I will also analyze the function and the expression of the gene(s) in the life cycle of the parasite and at different stages of the infection. My attention will also be focused on learning novel biochemical and molecular pathways and/or regulatory mechanisms that are unique for this parasite and could lead to new strategies for chemotherapeutic attack of this disease.

利什曼原虫物种已成为该研究的优秀模型系统 传染病的分子遗传学，除了它们的 作为人类病原体的重要性。我将采用遗传方法 功能互补来研究毒力特性 利什曼原虫。这一战略的成功已被证明 杜氏乳杆菌的几个突变系的互补缺乏 脂磷酸聚糖（LPG）是细胞表面毒力决定因素。我计划 使用此方法选择用于恢复毒力特性的其他 比LPG表达。我将用一组无毒的病毒感染 BALB/c 小鼠 L. 主要寄生虫，已用粘粒文库转染 寄生虫的剧毒菌株。只有那些恢复了原状的寄生虫 毒力将被允许抵抗小鼠的防御并形成 病变，可以从中恢复遗传和分子 分析。使用这种方法，我将追踪负责的基因 毒力增强。我也会分析一下函数和表达式 寄生虫生命周期中不同阶段的基因 的感染。我的注意力也会集中在学习小说上 生化和分子途径和/或调节机制 这种寄生虫是独一无二的，可能会导致新的策略 这种疾病的化疗发作。