Protein Core

蛋白质核心

• 批准号: 9899928
• 负责人: Trevor F Moraes
• 金额: $ 21.94万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9899928
• 关键词: Antigen Targeting; Antigens; Biophysics; Cell surface; Cells; Computer Models; Contracts; Core Protein; Cryoelectron Microscopy; Crystallography; Culture Media; Cytosol; Development; Disease; Engineering; Epitopes; Escherichia coli; Generations; Goals; Gonorrhea; Guidelines; Immune Evasion; Immune response; Immunology; Industrialization; Infection; Infrastructure; Lead; Lipoproteins; Location; Maps; Membrane; Membrane Proteins; Methodology; Methods; Microbiology; Modeling; Monoclonal Antibodies; Neisseria gonorrhoeae; Nutrient; Pathogenesis; Pathway interactions; Point Mutation; Production; Property; Protein Engineering; Protein Secretion; Proteins; Resolution; SLAM protein; Site; Structural Models; Structure; Surface; System; Testing; Therapeutic; Vaccine Antigen; Vaccine Design; Vaccine Production; Vaccines; Vision; Work; X-Ray Crystallography; antimicrobial; design; host colonization; immunogenic; immunogenicity; innovation; insight; instrumentation; novel therapeutics; novel vaccines; pathogen; pathogenic bacteria; periplasm; prevent; programs; prophylactic; protein expression; protein purification; scale up; structural biology; tool; vaccine development

Project Summary The overall goal of the Protein Core is to first provide atomic resolution structural and functional insight into the design and engineering of the proposed protein antigens from Neisseria gonorrhoeae. The second aim is to produce the antigens with high quality and quantity in an efficient and effective manner. We aim to provide high- resolution structural information using X-ray Crystallography and/or Cryo-Electron Microscopy and we plan to express and purify large quantities of pure protein using our recently discovered SLAM protein secretion system. Proteins residing the outer membrane surface of Gram-negative bacterial pathogens provide a valuable target for the generation of antimicrobial therapeutics and prophylactics. In pathogens, many of the outer membrane proteins are required for either nutrient acquisition or host immune evasion and therefore are essential for host colonization or during invasive disease. At the bacterial cell surface, these outer membrane proteins provide surface accessible epitopes that can serve as antigens in the implementation of vaccines against these pathogens—thus an understanding of their structure and function provides useful insights into the development of new therapeutics against Gram-negative pathogens. Dr. Moraes' program vision is to provide an avenue to develop and produce new vaccine antigens and a novel vaccine production system. The microbiological tools, instrumentation and infrastructure available to Dr. Moraes and his collaborators allow him to be productive and successful at contributing to the structural biology of membrane proteins particularly as is relates to bacterial pathogenesis and vaccine design.

项目概要 蛋白质核心的总体目标是首先提供原子分辨率的结构和功能洞察 所提出的淋病奈瑟氏菌蛋白质抗原的设计和工程。第二个目标是 以高效、有效的方式生产高质量、高产量的抗原。我们的目标是提供高 使用 X 射线晶体学和/或冷冻电子显微镜解析结构信息，我们计划 使用我们最近发现的 SLAM 蛋白分泌系统表达和纯化大量纯蛋白。 革兰氏阴性细菌病原体外膜表面的蛋白质提供了一个有价值的靶标 用于产生抗菌治疗剂和预防剂。在病原体中，许多外膜 蛋白质是获取营养或逃避宿主免疫所必需的，因此对于宿主来说至关重要 定植或侵袭性疾病期间。在细菌细胞表面，这些外膜蛋白提供 表面可及的表位可以作为针对这些疾病的疫苗实施中的抗原 病原体——因此了解它们的结构和功能可以为疾病的发展提供有用的见解 针对革兰氏阴性病原体的新疗法。 Moraes 博士的项目愿景是提供开发和生产新疫苗抗原和新型疫苗的途径 疫苗生产系统。 Moraes 博士可用的微生物工具、仪器和基础设施 和他的合作者使他能够高效并成功地为结构生物学做出贡献 膜蛋白尤其与细菌发病机制和疫苗设计有关。