Virulence Factor of Porphyromonas gingivalis

牙龈卟啉单胞菌的毒力因子

• 批准号: 6516674
• 负责人: Janina P Lewis
• 金额: $ 13.41万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-15 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6516674
• 关键词: Bacteroides gingivalis; bacterial proteins; binding sites; cysteine endopeptidases; enzyme activity; enzyme mechanism; enzyme structure; gene expression; gene mutation; genetic regulation; heme; hemoglobin; hemoprotein; iron metabolism; laboratory mouse; lysine; mass spectrometry; membrane transport proteins; oral bacteria; porphyrin biosynthesis; protein sequence; recombinant proteins; secretion; virulence

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.

描述：（由申请人提供）建议的K22职业发展计划 将允许Janina P.刘易斯博士完成一年的高级博士后 培训，然后过渡到终身助理教授职位， VCU飞利浦口腔和颅面分子生物学研究所。一个主要 学者发展阶段的一部分将用于参加正式课程， 生物物理技术和获得质谱学的实践经验， X射线晶体学和基于计算机的分子建模。本次培训 将发生在化学的VCU部门和VCU研究所为 结构生物学与药物设计在她进入教职员行列后 在VCU飞利浦研究所，刘易斯博士将有能力追求新的 研究牙周病原体中毒力因子的途径， 牙龈卟啉菌。到目前为止，她的研究集中在 赖氨酸特异性蛋白酶Kgp。她已经确定KGP是必不可少的， 氯化血红素在细菌表面积累的过程。虽然 氯高铁血红素深刻地影响牙龈卟啉单胞菌的毒力， 其摄取及其在遗传调节中的作用知之甚少。 这一目标的实现将促进对体育的认识。 牙龈炎在两个方面。首先，它将加深我们对 Kgp的分泌、物理和结构特性。第二，她将 基于她的观察，即Kgp以外的蛋白质参与了氯化血红素 和铁的吸收，以及全球调控网络控制表达。的 这项工作的结果将有助于确定氯化血红素摄取因子和调控因子。 这些因素可能是未来抗牙周炎策略的目标。的 知识和仪器培训资源， 该机构对刘易斯博士教师发展的承诺提供了一个高度 一个成功的过渡到教师阶段的支持性环境，这 这对她作为一名独立调查员的迅速发展是个好兆头。