TRANSCRIPTIONAL REGULATION OF TCPPH IN V.CHOLERAE

本申请详细介绍了细菌发病机理的两部分，为期五年的研究生涯发展计划。该项目将在Stephen B. Calderwood博士的指导下进行，他是马萨诸塞州波士顿市麻省总医院传染病科的医生。该候选人接受过传染病方面的培训，长期的职业目标是获得细菌发病机制方面的专业知识，特别强调基因调控。该计划将包括在哈佛医学院的实验室技术和微生物学和分子遗传学课程的教学。该计划的研究部分将集中在霍乱弧菌对环境信号的反应中毒力基因的转录调节。霍乱弧菌是一种被充分研究的细菌发病机制和基因调控模型。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，本项目的重点是进一步表征这种调控。研究的三个具体目标是：(1)进一步研究环境条件对霍乱弧菌经典型和El - Tor型两种生物型tcpPH启动子的转录调控；(2)在体外鉴定环境信号调控tcpPH转录所需的新蛋白；(3)寻找在体内感染过程中响应宿主环境激活tcpPH转录的新蛋白。导师和顾问委员会将监督申请人的进展和研究。该计划将使候选人获得技能，知识和经验，成为细菌发病机理的独立生物医学研究人员。

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.