Identification of proteins involved in the formation of Novel Permeation Pathways in the plasma membrane of the Plasmodium falciparum-infected erythrocyte

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The invasion of human erythrocytes by the malaria parasite Plasmodium falciparum induces novel permeation pathways in the plasma membrane of the infected cell which are not found in non-infected cells. These permeation pathways allow access of small solutes from the extraerythrocytic milieu which are essential for parasite growth. Although the physiological properties of novel permeation pathways have been investigated in considerable detail, the proteins involved in these pathways have not been identified. In the following project we plan to develop experimental strategies for the identification of proteins that contribute to the formation of the novel permeation pathways. These strategies are based on a selective labelling of surface proteins in infected and in non-infected erythrocytes. Proteins from infected erythrocytes which, owing to conformational changes, have a different pattern of labelled peptides, and proteins which are undetectable in non-infected erythrocytes will be analysed by MALDI-TOF-MS and their respective genes will be identified in genome data bases. The functional analysis of those candidate proteins will be performed after expression of the respective genes in heterologous systems.