ALTERATION OF THE ERYTHROCYTE MEMBRANE DURING MALARIA

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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.