The objective of this proposal is the development and utilization of electrophysiological methodologies to assess changes in hepatocyte membrane permeability during infection with Plasmodium parasites. The establishment of this methodology could help determine if new permeability pathways (NPP) are required for the development of liver stage parasites. The interaction of the different developmental stages of Plasmodium with the host, in which they reside, has been an active area of research for a number of reasons. The biology of the interaction is fascinating and understanding the relationship of the parasite with its host can lead to the rational development of successful intervention strategies. The approaches that investigators have taken to study the host-parasite relationship are as varied as the different stages. Genomic, proteomic and functional based approaches have been utilized. Each has its advantages and it is most likely the sequencing of several Plasmodium genomes that has allowed investigators to attempt rational functional analysis of parasite gene expression. Recent functional studies have sought to identify NPPs, in Plasmodium infected erythrocytes that may be responsible for the increased permeability of the infected red blood cell membrane. Several examples of NPPs have been identified by multiple methods, however there is virtually no research to suggest that the parasite can modify the hepatocyte membrane. The studies outlined in this proposal are novel and will attempt to identify NPPs in Plasmodium infected hepatocytes and provide a functional significance for these modifications in the context of the parasites intracellular growth and development. The demonstration of parasite induced hepatocyte membrane modifications would not only add to our understanding of Plasmodium metabolic processes, but could serve to validate potential targets for chemotherapeutic agents.
The demonstration of Plasmodium induced hepatocyte membrane modifications would not only add to our understanding of the metabolic processes that occur during development of the parasite in the hepatocyte, but could serve to validate potential targets for chemotherapeutic agents. This could provide a novel approach for the prophylaxis and treatment of malaria.
