STRUCTURAL STUDIES OF HUMAN HOOKWORM VACCINE CANDIDATES

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 人类钩虫病是一种毁灭性的疾病，也是发展中国家失血和缺铁性贫血的主要原因。 人类钩虫感染影响约10亿人，其中许多是儿童，导致身体发育迟缓、智力发育不良和生活质量下降。这种疾病是由寄生线虫引起的，其具有复杂的生命周期，包括自由生活阶段。钩虫是最致病的土壤传播蠕虫。钩虫也是伪装大师，感染后产生抗原，促进逃避和抑制宿主的免疫系统。 钩虫引起的免疫抑制导致更容易感染其他疾病，包括疟疾、肺结核和艾滋病毒/艾滋病。传统的钩虫控制和根除方法在很大程度上失败了，需要开发新的治疗方法来对抗这种毁灭性的疾病。目前正在努力开发新的工具来控制钩虫感染，包括钩虫疫苗开发计划（人类钩虫疫苗倡议，HHVI）。HHVI鉴定了来自感染性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点的结构研究。 我们的第二个研究是涉及细胞死亡的膜蛋白的三维X射线结构研究。 没有已知的孔蛋白/抗孔蛋白或其他类似膜蛋白的三维结构。 实验正在我们的实验室进行，我们的合作者可能会产生一些这样的结构。 我们的目标是从S解出Cid A，Cid B，Lrg A和Lrg B的结构. aureus和B.炭疽病 我们的第三个研究是BChE的药物解毒机制。

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.