INHIBITION OF PLASMODIUM/HEPATOCYTE INTERACTION

疟疾是世界上最重要的传染病之一。这个 世界卫生组织估计有2.7亿个新病例 每年都有疟疾的风险。尽管控制方面的努力最初遇到了 一些成功，蚊子对杀虫剂和 从寄生虫到化疗药物的转变使得寻找新的 问题的解决方案。 子孢子上的配体，寄生虫的感染阶段，用于 肝细胞是最近被描述的细胞。内科医生的第一阶段 科学家奖将侧重于获得多肽化学和 应用它们精确确定一级结构和二级结构 疟疾子孢子对肝细胞的配基。这次培训将是 辅以蛋白质化学和免疫学的课程作业 以及细胞生物学研讨会，这些研讨会将在该项目的第二阶段有用。 第一阶段将应用第一阶段期间产生的结果，以尝试 抑制子孢子侵入肝细胞，从而预防疟疾 感染。努力将重点放在使用噬菌体组合库来 制备抗子孢子配基的单抗，并在 新型合理多肽疫苗的研制 肝细胞的子孢子感染性。 提出的研究将有助于对生物学的理解 疟疾寄生虫的防治和疾病预防。教育性和 医生科学家奖的研究目标将为医生提供 具有独立从事基础研究的基础的申请者 寄主-寄生虫的相互作用，强调生物化学和 免疫学。

Malaria is one of the most important infectious diseases in the world. The World Health Organization estimates that there are 270 million new cases of malaria every year. Although efforts at control initially met with some success, the increasing resistance of mosquitos to insecticides and of parasites to chemotherapeutic agents makes it imperative to find new solutions to the problem. The ligand on sporozoites, the infective stage of the parasite, for hepatocytes has recently been described. Phase I of the Physician Scientist Award will focus on acquiring skills in peptide chemistry and applying them to precisely determine the primary and secondary-structure of the malaria sporozoite ligand for hepatocytes. This training will be supplemented with course work in protein chemistry as well as immunology and cell biology seminars that will be useful in Phase II of this project. Phase Il will apply the results generated during Phase I in an attempt to inhibit sporozoite invasion of hepatocytes and thereby prevent malaria infection. Efforts will focus on using a phage combinatorial library to make monoclonal antibodies to the sporozoite ligand, and on the development of new and rational peptide vaccines aiming at inhibition of sporozoite infectivity of hepatocytes. The studies proposed will contribute to the understanding of the biology of malaria parasites and to disease prophylaxis. The educational and research goals of the Physician Scientist Award will provide the physician applicant with the foundation to independently continue basic research in host-parasite interactions with an emphasis on biochemistry and immunology.