MOLECULAR AND CELL BIOLOGY OF CHLAMYDIA TRACHOMATIS

沙眼衣原体的分子和细胞生物学

• 批准号: 2429342
• 负责人: Joanne N. Engel
• 金额: $ 6.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2429342
• 关键词: Chlamydia trachomatis; DNA footprinting; Escherichia coli; Saccharomyces cerevisiae; bactericidal immunity; biological signal transduction; cell cell interaction; cellular pathology; confocal scanning microscopy; endocytosis; genetic promoter element; genetic regulation; genetic transcription; host organism interaction; intracellular parasitism; liposomes; microorganism genetics; microorganism immunology; molecular pathology; phagocytes; phosphorylation; protein purification; transcription factor; vesicle /vacuole

Joanne Engel, M.D., Ph.D. is an assistant professor in the Department of Medicine at UCSF. Her long-term interests center upon bacterial pathogenesis as it relates to Infectious Diseases; her short term goals are to study the pathogenesis of chlamydial infections. Her graduate and postdoctoral training in Molecular and Cell Biology combined with her clinical training in Internal Medicine and infectious Diseases affords her a thorough background and a unique perspective to pursue these studies. She has a fully equipped lab in the Division of Infectious Diseases and the full support of the Department of medicine for her research. She has co- appointments in the two major graduate programs, giving her the opportunity to train exceptional graduate students. She has extensive interactions and collaborations with faculty and labs in the Biochemistry, Genetics, and Cell Biology Divisions. The next 5 years are critical to her maturation as a basic scientist and her ability to maintain a first-class research effort. An RCDA award would facilitate this by significantly decreasing her clinical load and teaching obligations, so that she may devote 85% of her time to research. The remaining 15% time will be devoted to research- related activities including clinical duties (that would allow her to maintain the clinical skills and expertise necessary for her research) and teaching. Chlamydia trachomatis is the leading cause of sexually transmitted diseases in the country and a major cause of blindness in third world countries. There are several unique aspect of the life cycle of this obligate intracellular parasite of humans that are key to its pathogenesis. These include (i) its unusual intracellular developmental life cycle and (ii) its ability to enter a non-phagocytic epithelial cell and survive within the hostile intracellular environment of the eukaryotic cytoplasm sequestered within a membrane bound compartment which evades fusion with lysosomes. The intimate interactions between chlamydia and its eukaryotic host are likely to involve natural biological pathways of the eukaryotic cell that the parasite usurps for its own survival. Remarkably little is known about chlamydial gene regulation or chlamydia-eukaryotic cell interactions, in part due to the difficulty in growing large quantities of the organism in tissue culture, the lack of chlamydial mutants, and the failure to develop a viable gene transfer system despite intense efforts, culminating in the inability to genetically manipulate these organisms. Study of these processes will yield insights into chlamydial disease pathogenesis as well as insights into eukaryotic cell biology. The proposal seeks to (i) develop an in vitro system to dissect the control of transcription initiation in Chlamydia (ii) explore the mechanisms by which chlamydia avoids lysosomal destruction and (iii) understand the interaction between chlamydia and the host cell signal transduction pathways. From these studies may emerge new therapeutic approaches to treating or preventing chlamydial infections.

乔安妮·恩格尔（Joanne Engel），医学博士是该系的助理教授 UCSF的医学。 她的长期兴趣集中在细菌上 与传染病有关的发病机理；她的短期目标是 研究衣原体感染的发病机理。 她的毕业生和 分子和细胞生物学的博士后训练与她结合 内科和传染病的临床培训为她提供 彻底的背景和独特的观点，可以追求这些研究。 她在传染病和 医学系全力支持她的研究。 她有共同 在两个主要的研究生课程中的约会，给了她机会 培训杰出的研究生。 她有广泛的互动， 在生物化学，遗传学和 细胞生物学划分。 接下来的5年对于她的成熟至关重要 基本科学家及其维持一流研究的能力 努力。 RCDA奖将通过大幅减少来促进这一点 她的临床负担和教学义务，以便她可以投入85％ 她的研究时间。 其余15％的时间将用于研究 - 相关活动，包括临床职责（这将使她能够 保持她的研究所必需的临床技能和专业知识）和 教学。 沙眼衣原体是性传播疾病的主要原因 在该国，是第三世界国家失明的主要原因。 这种义务的生命周期有几个独特的方面 人类的细胞内寄生虫是其发病机理的关键。 这些 包括（i）其非同寻常的细胞内发育生命周期和（ii） 能够进入非噬细胞上皮细胞并在 真核细胞质的敌对细胞内环境隔离 在一个与溶酶体融合的膜结合区内。 衣原体与其真核宿主之间的亲密互动是 可能涉及真核细胞的自然生物学途径 寄生虫篡夺了自己的生存。 关于 衣原体基因调节或衣原体 - 核细胞相互作用，在 部分是由于难以在大量生物中生长 组织培养，缺乏衣原体突变体以及未能发展的 尽管付出了巨大的努力，但可行的基因转移系统仍在 无法遗传操纵这些生物。 这些研究 过程还将对衣原体疾病发病机理产生见解 作为对真核细胞生物学的见解。 该提议寻求（i） 开发一个体外系统来剖析转录的控制 衣原体的启动（II）探索了衣原体的机制 避免溶酶体破坏和（iii）了解 衣原体和宿主细胞信号转导途径。 从这些 研究可能会出现新的治疗方法来治疗或预防 衣原体感染。