ALTERATION OF THE ERYTHROCYTE MEMBRANE DURING MALARIA

疟疾寄生虫在其红细胞期改变宿主的 膜的 由于红细胞膜的改变可能是 寄生虫生存所必需的，更好地了解 宿主和寄生虫之间的相互作用将提供对新的 治疗方法。 拟议的长期目标 研究是为了表征和更好地理解 寄生虫和红细胞膜之间的分子或 生化水平。 特别是寄生虫来源的蛋白质， 与宿主红细胞膜相关，将进行研究。 一 该计划的一个具体目标是克隆和测序基因， 三个以前表征的酸性磷蛋白从啮齿动物 疟疾寄生虫与细胞质面相互作用， 红细胞膜 93 kDa疟原虫的λ gt 11克隆 chabuadi酸性磷蛋白已经被分离出来，65和 将通过筛选克隆46 kDa伯氏疟原虫酸性磷蛋白 具有合成寡核苷酸的重组DNA文库（基于 蛋白质的氨基酸序列）。 酸的序列 磷蛋白将提供有关它们的结构和它们的 与其他蛋白质的关系 克隆的基因也将被用作 探针检测酸性磷蛋白在人体内的分布 疟疾物种，从而提供了一个框架， 人类疾病的情况，并提供有关 宿主-寄生虫相互作用 克隆基因的长期计划包括 生产大量重组蛋白用于 功能研究。 此外，可用的单克隆抗体 将被用来定位酸性磷蛋白上的 超微结构水平，并探讨其机制 酸性磷蛋白从寄生虫运输到 通过脉冲追踪实验检查红细胞膜。 在 总而言之，拟议的研究将提供有关 结构、功能和运输机制的酸性 磷蛋白 这些结果将有助于我们了解 宿主-寄生虫相互作用的分子生物学， 导致新的治疗方法的发展。 此外，委员会认为， 此类研究将提供有关结构和功能的信息 膜一般。

The malarial parasite, during its erythrocytic stage, alters the host's membrane. Since the alterations of the erythrocyte membrane are probably necessary for parasite survival, a better understanding of the interactions between host and parasite will provide insight into novel therapeutic approaches. The long-term objectives of the proposed research are to characterize and better understand the interactions between the parasite and the erythrocyte membrane on a molecular or biochemical level. In particular, proteins of parasite origin, but associated with the host erythrocyte membrane, will be investigated. One of the specific aims of the proposal is to clone and sequence the genes of three previously characterized acidic phosphoproteins from rodent malarial parasites that interact with the cytoplasmic face of the erythrocyte membrane. A lambda gt11 clone of the 93 kDa Plasmodium chabuadi acidic phosphoprotein has already been isolated, and the 65 and 46 kDa P. berghei acidic phosphoproteins will be cloned by screening recombinant DNA libraries with synthetic oligonucleotides (based upon the amino acid sequences of the proteins) . The sequences of the acidic phosphoproteins will provide information about their structures and their relatedness to other proteins. The cloned genes will also be used as probes to examine the distribution of the acidic phosphoproteins in human malarial species, thus providing a framework for applications to the human disease situation and providing information about the evolution of host-parasite interactions. Long-term plans for the cloned genes include the production of large quantities of recombinant proteins to be used in functional studies. In addition, the available monoclonal antibodies will be used to localize the acidic phosphoproteins on the ultrastructural level using immuno-electron microscopy, and the mechanism of transport of the acidic phosphoproteins from the parasite to the erythrocyte membrane will be examined by pulse-chase experiments. In summary, the proposed studies will provide information concerning the structures, functions, and mechanism of transport of the acidic phosphoproteins. These results will contribute to our knowledge about the molecular biology of host-parasite interactions and may eventually lead to the development of novel therapeutic approaches. Furthermore, such studies will provide information about the structure and function of membranes in general.