STRUCTURAL STUDIES OF HUMAN HOOKWORM VACCINE CANDIDATES

人类钩虫疫苗候选物的结构研究

• 批准号: 7601600
• 负责人: OLUWATOYIN Ajibola ASOJO
• 金额: $ 0.28万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601600
• 关键词: 3-Dimensional; AIDS/HIV problem; Adult; Affect; Antigens; Bacillus anthracis; Cell Death; Child; Complex; Computer Retrieval of Information on Scientific Projects Database; Disease; Drug Delivery Systems; Drug Metabolic Detoxication; Funding; Grant; Growth; Hemorrhage; Hookworm Infections; Hookworms; Human; Immune; Immune system; Infection; Institution; Iron deficiency anemia; Laboratories; Life; Life Cycle Stages; Malaria; Membrane Proteins; Methods; Parasitic nematode; Process; Psyche structure; Quality of life; Research; Research Personnel; Resources; Roentgen Rays; Soil; Source; Staging; Staphylococcus aureus; Structure; Tuberculosis; United States National Institutes of Health; Vaccine Antigen; Vaccines; beamline; drug mechanism; novel; novel therapeutics; programs; research study; three dimensional structure; tool; vaccine development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human hookworm disease is a devastating disease and a major source of blood-loss and iron-deficiency anemia in the developing world. Human hookworm infection affects about one billion people, many of them children, leading to stunted physical growth, mental underdevelopment and reduced quality of life. This disease is caused by parasitic nematodes with a complex life cycle which includes a free-living stage. Hookworms are the most pathogenic soil-transmitted helminthes. Hookworms are also masters of disguise that upon infection produce antigens that facilitate the evasion and suppression of the host¿s immune system. Immune suppression by hookworms leads to easier infection by other diseases, including malaria, tuberculosis, and HIV/AIDS. Conventional methods of hookworm control and eradication have largely failed and there is a need to develop new therapeutics to combat this devastating disease. There are on-going efforts to develop new tools to control hookworm infection, including a hookworm vaccine development program (The Human Hookworm Vaccine Initiative, HHVI). The HHVI identified candidate vaccine antigens from the infective L3 as well as from the adult stage. We are in the process of crystallizing and solving the structures of some of these vaccine candidates. Beamline access will facilitate our ongoing structural studies of novel hookworm vaccines and drug targets. Our second study is the 3-dimensional X-ray structural studies of membrane proteins involved in cell death. There are no known 3-dimensional structures of holins / anti-holins or other similar membrane proteins. Experiments are underway in our laboratory and that of our collaborators that may generate some of these structures. Our objective is to solve the structures of Cid A, Cid B, Lrg A and Lrg B from S. aureus and B. anthracis. Our third study is the mechanisms of drug detoxification by BChE.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 人钩虫病是一种毁灭性的疾病，是发展中国家血液和铁缺陷性贫血的主要来源。人类钩虫感染影响了大约十亿人，其中许多是孩子，导致身体成长阻碍，精神欠发育和生活质量降低。该疾病是由具有复杂生命周期的寄生线虫引起的，其中包括自由生活阶段。钩虫是最致病的土壤传播的舵手。钩虫也是伪装的大师，即感染产生抗原，促进宿主免疫系统的逃避和抑制。钩虫的免疫抑制会导致其他疾病的感染更容易，包括疟疾，结核病和艾滋病毒/艾滋病。传统的钩虫控制和放疗方法在很大程度上失败了，需要开发新的治疗剂来打击这种毁灭性的疾病。正在进行的努力开发新工具以控制钩虫感染，包括钩虫疫苗开发计划（HHVI人类钩虫疫苗倡议）。 HHVI鉴定了来自感染力L3以及成人阶段的候选疫苗抗原。我们正在结晶和解决其中一些疫苗候选物的结构。光束线的获取将促进我们正在进行的新型钩虫疫苗和药物靶标的结构研究。 我们的第二项研究是与细胞死亡有关的膜蛋白的三维X射线结构研究。霍林斯 /抗霍林斯或其他类似的膜蛋白没有已知的三维结构。我们的实验室和我们的合作者的实验正在进行中，这些实验可能会产生其中一些结构。我们的目的是解决来自金黄色葡萄球菌和炭疽杆菌的CID A，CID B，LRG A和LRG B的结构。 我们的第三项研究是BCHE的药物解毒机制。