HPMI: Host Pathogen Mapping Initiative

HPMI：宿主病原体绘图计划

• 批准号: 10453911
• 负责人: Nevan J Krogan
• 金额: $ 100万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453911
• 关键词: Age; Antibiotics; Arts; Attention; Bacteria; Bacterial Infections; Binding; Biological; Biological Process; Biology; California; Cell Line; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chlamydia trachomatis; Clinical; Communicable Diseases; Complex; Computer Analysis; Computer software; Computing Methodologies; Databases; Face; Future; Gene Proteins; Genes; Goals; Infection; Infectious Diseases Research; Integration Host Factors; Knowledge; Laboratories; Logic; Maps; Mission; Modality; Modeling; Molecular; Mycobacterium tuberculosis; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Phase Transition; Principal Investigator; Proteins; Research; Research Personnel; Resources; Sampling; San Francisco; Science; Scientist; Staphylococcus aureus; System; Systems Biology; Technology; Therapeutic; Therapeutic Intervention; Training; Universities; Work; bacterial resistance; drug resistant pathogen; fighting; microbial; molecular modeling; next generation; novel; novel strategies; novel therapeutics; pathogen; protein complex

THE HOST PATHOGEN MAP INITIATIVE: A NATIONAL RESEARCH CENTER FOR SYSTEMS BIOLOGY OF INFECTIOUS DISEASE OVERALL SUMMARY Antibiotic-resistant pathogens are no longer an “emerging” threat as we face the reality of a return to the pre-antibiotic age where treatments for the simplest microbial infections are ineffective. The Centers for Disease Control and Prevention (CDC) estimates that more than 2 million people acquire a serious resistant bacterial infection each year, and at least 23,000 deaths result. These numbers will increase dramatically as our ability to fight these infections diminishes. Unfortunately, there have been no novel classes of antibiotics discovered since the 1960s, underscoring the fact that novel approaches are required to develop novel therapies to treat infection. As a result of these facts, it is now being realized that efforts to develop host-directed therapies to treat infectious diseases may have unique advantages. Also, recent work has revealed that although similar proteins may not be targeted by different pathogens, the same functional pathways are often hijacked and re-wired during the course of infection. For these reasons, the study of infectious disease is becoming increasingly dependent on knowledge of biological networks of multiple types, including physical interactions among proteins and synthetic-lethal and epistatic interactions among genes, which allow for deconstruction of functional pathways. Here we seek support for a new effort, termed The Host Pathogen Map Initiative (HPMI) (http://www.hpmi.ucsf.edu), aimed at comprehensively detailing the complex interactions among pathogenic genes and proteins with the host factors they hijack and rewire during the course of infection. The HPMI is a multi-campus initiative of the University of California, centered at UC San Francisco and UC-Berkeley, which leverages advanced network mapping, computational analysis and infectious disease research platforms developed by multiple HPMI investigators over the past decade. Thus primed, these platforms will be turned to efficiently generate, assemble, and analyze host-pathogen molecular networks with a view towards using this information in a clinical setting. Over the next five years, the HPMI will seek to catalyze major phase transitions in pathogenesis research by (1) Comprehensively mapping the networks of physical interactions using sets of secreted proteins from three bacteria; Mycobacterium tuberculosis (Mtb), Staphylococcus aureus (SA) and Chlamydia trachomatis (CT) with their host, revealing the protein complexes and higher-order molecular units targeted by these pathogens; (2) Mapping the parallel networks of synthetic-lethal and epistatic interactions among the genes being targeted by the bacteria, revealing the functional logic of pathogenesis; (3) Establishing the robust computational methodology, end-user software, and databases for assembly and use of host-pathogen network maps in both basic and clinical modalities; (4) Building a critical mass of leading infectious disease investigators worldwide to expand HPMI into a global coordinated partnership; and (5) Training the current and next-generation of scientists in Network Biology and its applications to infectious disease research.

宿主病原体图计划： 国家感染系统生物学研究中心 疾病 总结 当我们面对重返现实时，抗生素耐药的病原体不再是“新兴”的威胁 抗生素年龄，最简单的微生物感染治疗无效。中心 疾病控制与预防（CDC）估计，超过200万人获得了严重的抵抗力 每年细菌感染，至少23,000人死亡。这些数字将大大增加 我们对抗这些感染的能力减少了。不幸的是，没有新颖的抗生素类 自1960年代以来发现，强调了开发新颖的方法的事实 治疗感染的疗法。由于这些事实，现在已经意识到了发展的努力 以宿主为导向的治疗传染病的疗法可能具有独特的优势。而且，最近的工作有 表明尽管类似的蛋白质可能不会被不同的病原体靶向，但相同的功能 在感染过程中，通常会被劫持和重新连接。由于这些原因，研究 传染病越来越依赖于多种类型的生物网络知识， 包括蛋白质之间的物理相互作用以及基因之间的合成致死和上皮相互作用， 允许解构功能途径。 在这里，我们寻求支持新的努力，称为《宿主病原体图计划》（HPMI） （http://www.hpmi.ucsf.edu），旨在全面详细介绍致病性之间的复杂相互作用 在感染过程中，基因和蛋白质与宿主因素的重新连接。 HPMI是一个 加利福尼亚大学的多校区倡议，以旧金山加州大学和加州大学伯克利分校为中心 利用高级网络映射，计算分析和传染病研究平台 在过去的十年中，由多个HPMI调查人员开发。这是备用的，这些平台将转向 有效地生成，组装和分析宿主 - 病原体分子网络，以期为此 在临床环境中的信息。 在接下来的五年中，HPMI将寻求通过 （1）全面地使用三个分泌蛋白的物理互动网络映射 细菌;结核分枝杆菌（MTB），金黄色葡萄球菌（SA）和沙眼衣原体（CT）（CT） 他们的宿主揭示了这些病原体靶向的蛋白质复合物和高阶分子单位。 （2） 绘制合成致死和上皮相互作用的平行网络。 细菌揭示了发病机理的功能逻辑； （3）建立强大的计算 方法，最终用户软件和数据库，用于组装和使用宿主 - 病原网络图 基本和临床方式； （4）在全球建立大量领先的传染病研究人员 将HPMI扩展到全球协调的合作伙伴关系； （5）培训当前和下一代 网络生物学的科学家及其在传染病研究中的应用。