Quorum-sensing mechanisms of Campylobacter

描述(由申请者提供)：本提案详细说明了一项为期三年的培训资助，重点是在分子食品安全微生物学领域发展一名独立的研究人员。首席调查员已经完成了兽医大动物内科的结构化实习，并获得了美国兽医内科学院在该专业的董事会认证。他现在正在积极进行分子微生物学领域的强化培训，以补充他在大型动物传染病方面的专业知识。 该项目旨在提供广泛的经典和现代分子技术，适用于食品安全微生物学中假说驱动的研究。通过弯曲杆菌分子微生物学领域的领军人物张启静博士的指导，首席研究员将培养他制定深思熟虑的假设的能力，设计稳健的实验来验证这些假设，并与同行交流科学结果。将特别重视负责任的研究行为方面的培训。在完成课程后，预计他将为独立的学术研究生涯做好准备。 作为这项提案的一部分，进行的研究将集中在空肠弯曲菌所使用的群体感应机制上，空肠弯曲菌是美国人类食源性细菌性肠炎的主要原因。自体诱导物-2(AI-2)介导的细菌通讯已在30多个细菌物种中被描述，并负责协调各种适应性反应的表达。基于主要研究者设计和进行的初步研究结果，本研究将1)确定G92D氨基酸替换对空肠弯曲菌LuxS蛋白酶活性的影响，2)鉴定受AI-2调控的双组分传感器系统(与大肠杆菌的磷响应双组分传感器系统同源)，以及3)通过体外和体内实验检测LuxS零突变对弯曲杆菌适应不同环境的影响。这些研究的结果将首次全面描述弯曲杆菌中的这一信号系统，并将为研究者未来的独立研究努力提供坚实的基础。 爱荷华州立大学兽医微生物学和预防医学系在食品安全和公共卫生微生物学领域处于领先地位。该大学和当地美国农业部国家动物疾病中心的资源相结合，提供了一个在兽医领域拥有无与伦比的专业知识和知识的环境。鉴于导师的实验室在研究领域的专业知识、肥沃的科学环境和强有力的机构承诺，这一培训计划肯定会成功。

DESCRIPTION (provided by applicant): This proposal details a three year training grant focused on development of an independent investigator in the field of molecular food safety microbiology. The principal investigator has completed a structured residency in Veterinary Large Animal Internal Medicine and is board certified by the American College of Veterinary Internal Medicine in this specialty. He is now actively pursuing intensive training in the field of molecular microbiology to complement his expertise in large animal infectious disease. This program is designed to provide exposure to a broad range of classical and contemporary molecular techniques applicable to hypothesis driven research in food safety microbiology. Through the mentorship of Dr. Qijing Zhang, a leader in the field of Campylobacter molecular microbiology, the principal investigator will develop his ability to formulate thoughtful hypotheses, design robust experiments to test these hypotheses and communicate scientific results with peers. Special emphasis will be placed on training in responsible conduct of research. At the completion of the program it is expected that he will be prepared for an independent career in academic research. Research conducted as part of this proposal will focus on the quorum sensing mechanism employed by Campylobacter jejuni, a leading cause of human foodborne bacterial enteritis in the United States. Autoinducer-2 (AI-2) mediated bacterial communication has been described in over 30 bacterial species and is responsible for coordinating expression of a variety of adaptive responses. Building on the results of preliminary research designed and conducted by the principal investigator, this study will 1) determine the effect of the G92D amino acid substitution on the enzymatic activity of the C. jejuni LuxS protein, 2) characterize a two-component sensor system (homologous to a phosphorus responsive two-component sensor system of E. coli) regulated by the presence of AI-2, and 3) examine the effects of the luxS null mutation on the adaptation of Campylobacter to various environments using in vitro and in vivo experiments. Results of these studies will provide the first comprehensive description of this signaling system in Campylobacter and will provide a strong foundation for future independent research endeavors by the investigator. The Department of Veterinary Microbiology and Preventative Medicine at Iowa State University is a leader in food safety and public health microbiology. The combined resources of the University and the local USDA National Animal Disease Center provide an environment rich in expertise and learning unmatched in the veterinary field. Given the expertise of the mentor's laboratory in the field of study, the fertile scientific environment, and a strong institutional commitment, this training program is assured success.