TRANSCRIPTIONAL REGULATION OF TCPPH IN V.CHOLERAE

这项申请详细说明了细菌发病机制的两部分，五年的研究生涯发展计划。该计划将在马萨诸塞州波士顿马萨诸塞州总医院传染病科斯蒂芬·B·卡尔德伍德博士的指导下进行。应聘者受过传染病方面的培训，并有长期的职业目标，即获得细菌发病机制方面的专业知识，特别强调基因调控。该计划将包括哈佛医学院的实验室技术教学以及微生物学和分子遗传学课程。该计划的研究部分将侧重于霍乱弧菌毒力基因对环境信号的转录调控。霍乱弧菌是研究细菌致病机制和基因调控的重要模型。霍乱弧菌调控基因的一个操纵子tcpPH在转录水平上受温度和pH的调控，该项目专注于进一步表征这一调控。本研究的三个具体目标是：(1)进一步研究环境条件对两种霍乱弧菌(经典霍乱弧菌和El Tor霍乱弧菌)中tcpPH启动子转录的调控；(2)在体外寻找环境信号调控tcpPH转录所必需的新蛋白；(3)寻找体内感染时激活tcpPH转录的新蛋白。导师和咨询委员会将监督申请者的进展和研究。该计划将允许候选人获得技能，知识和经验，成为一名独立的生物医学研究人员在细菌发病机制。

This application details a two-part, five year research career development program in bacterial pathogenesis. The program will be conducted under the guidance of Dr. Stephen B. Calderwood, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA. The candidate is trained in Infectious Diseases and has the long-term career goals of gaining expertise in bacterial pathogenesis, with special emphasis on gene regulation. The program will include sessions of instruction in laboratory techniques and courses in microbiology and molecular genetics at Harvard Medical School. The research component of the program will focus on transcriptional regulation of virulence genes in Vibrio cholerae in response to environmental signals. V. cholerae is a well-studied model for bacterial pathogenesis and gene regulation. One operon of regulatory genes in V. cholerae, tcpPH, is regulated at the transcriptional level by temperature and pH, and the project focuses on further characterization of this regulation. Three specific aims will be addressed: (1) to further investigate transcriptional regulation at the tcpPH promoter by environmental conditions in the two biotypes of V. cholerae, classical and El Tor; (2) to identify novel proteins necessary for regulation of tcpPH transcription by environmental signals in vitro; and (3) to find novel proteins which activate tcpPH transcription in response to the host environment during in vivo infection. The mentor and an advisory committee will oversee the applicant's progress and research. The program will allow the candidate to obtain the skills, knowledge, and experience to become an independent biomedical researcher in bacterial pathogenesis.