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Core-002

核心002

基本信息

批准号：
10330126
负责人：
CYNTHIA N CORNELISSEN
金额：
$ 8.29万
依托单位：
GEORGIA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-25 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10330126
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

项目摘要

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.

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的见解，设计和工程化来自淋病奈瑟氏菌的所提出的蛋白抗原。第二个目标是高效、优质、大量地生产抗原。我们的目标是提供高分辨率使用X射线晶体学和/或冷冻电子显微镜的结构信息，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微生物治疗剂和抗菌剂。在病原体中，许多外膜蛋白质是营养获取或宿主免疫逃避所必需的，因此对于宿主来说是必需的。殖民化或侵入性疾病期间。在细菌细胞表面，这些外膜蛋白提供表面可及表位可在针对这些抗原的疫苗的实施中用作抗原，因此，了解它们的结构和功能，可以为了解病原体的发展提供有用的见解。革兰氏阴性病原体的新疗法。博士Moraes的计划愿景是提供一种开发和生产新疫苗抗原的途径，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富有成效地为结构生物学做出贡献，膜蛋白，特别是涉及细菌发病机理和疫苗设计。