Virulence Factor of Porphyromonas gingivalis

描述：(由申请人提供)拟议的K22职业发展计划将允许Janina P.Lewis博士完成一年的高级博士后学习 培训，然后过渡到终身教席助理教授职位 弗吉尼亚州立大学飞利浦口腔和颅面分子生物学研究所。一位少校 学者发展阶段的部分时间将用于参加正式课程。 生物物理技术和在质谱学方面的实践经验， X射线结晶学和基于计算机的分子建模。这次培训 将在VCU化学系和VCU研究所举行 结构生物学与药物设计。在她进入教职员工队伍后 在VCU飞利浦研究所，刘易斯博士将处于有利地位，寻求新的 牙周病原体致病因子的研究途径， 牙龈卟啉单胞菌。迄今为止，她的研究主要集中在 赖氨酸专一性蛋白酶，KGP。她认为KGP在中国是不可或缺的 在细菌表面积累氯化血红素的过程。虽然 氯化血红素深刻影响牙龈假单胞菌的毒力，其机制涉及 它的摄取及其在基因调控中的作用还知之甚少。 这一建议的目的的实现将促进对体育运动的认识。 牙周炎有两个方面。首先，它将加深我们对 KGP的分泌、物理和结构性质。第二，她应该 根据她的观察，KGP以外的蛋白质参与了氯化血红素 和铁摄取，全球监管网络控制着表达。这个 这项工作的结果将有助于确定氯化血红素摄取因子和调节 未来可能成为抗牙周炎策略靶点的元素。这个 智力和仪器设备培训资源与 学院对刘易斯博士教师发展的承诺提供了高度的 为成功过渡到本课程的教师阶段提供支持性环境 获奖，这对她作为一名独立调查员的快速发展是个好兆头。

DESCRIPTION: (provided by applicant) The proposed K22 career development plan will allow Dr. Janina P. Lewis to complete a year of advanced postdoctoral training, and then transition into a tenure-track assistant professorship in VCU Philips Institute of Oral and Craniofacial Molecular Biology. A major portion of the scholar development phase will be spent taking formal courses in biophysical techniques and gaining hands-on experience in mass spectroscopy, X-ray crystallography, and computer-based molecular modeling. This training will take place in the VCU Department of Chemistry and the VCU Institute for Structural Biology and Drug Design. Upon taking her place in the faculty ranks at the VCU Philips Institute, Dr. Lewis will be well positioned to pursue new avenues for studying virulence factors in the periodontal pathogen, Porphyromonas gingivalis. To date her research has centered on the lysine-specific protease, Kgp. She has determined that Kgp is indispensable in the process of accumulation of hemin on the surface of the bacteria. Although hemin profoundly affects virulence of P. gingivalis, the mechanisms involved in its uptake and its role in genetic regulation are poorly understood. Accomplishment of the aims of this proposal will advance the knowledge of P. gingivalis on two fronts. First, it shall deepen our knowledge about the secretion of, physical and structural properties of Kgp. Second, she shall build on her observations that proteins other than Kgp are involved in hemin and iron uptake, and that global regulatory networks control expression. The results of this work will help define hemin uptake factors and regulatory elements that may be future targets of antiperiodontitis strategies. The intellectual and instrumentation training resources coupled with the institution's commitment to Dr. Lewis' faculty development provides a highly supportive environment for a successful transition to the faculty phase of this award, and bodes well for her rapid development as an independent investigator.