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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人类钩虫病是一种破坏性疾病，也是发展中国家失血和缺铁性贫血的主要来源。人体钩虫感染影响了大约10亿人，其中许多是儿童，导致身体发育迟缓、智力发育不足和生活质量下降。这种疾病是由寄生线虫引起的，其生活史复杂，包括自由生活阶段。钩虫是最具致病性的土传蠕虫。钩虫也是伪装大师，感染后会产生抗原，便于逃避和抑制宿主S的免疫系统。钩虫的免疫抑制导致更容易感染其他疾病，包括疟疾、结核病和艾滋病毒/艾滋病。传统的钩虫控制和根除方法在很大程度上已经失败，需要开发新的疗法来抗击这种毁灭性的疾病。目前正在努力开发控制钩虫感染的新工具，包括钩虫疫苗开发计划(人类钩虫疫苗倡议，HHVI)。HHVI确定了来自感染性L3和成体阶段的候选疫苗抗原。我们正在结晶和解决其中一些候选疫苗的结构。光束线接入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参与细胞死亡的膜蛋白的三维X射线结构研究。目前还没有已知的Holins/anti-holins或其他类似膜蛋白的三维结构。我们的实验室和我们的合作者正在进行实验，可能会产生其中的一些结构。我们的目标是从金黄色葡萄球菌和炭疽杆菌中分离出Cid A、Cid B、LRG A和LRG B的结构。 我们的第三个研究是BCHE的戒毒机制。