Recent years have seen an immense success in genomic and proteomic analyses of parasites. Despite this great advance in technology, understanding the biological function of a given protein still requires individual cell biological studies to fully value the importance of this protein. We recently have identified two membrane proteins from Plasmodium falciparum which both carry a histidine tail and are exported from the parasite through the parasitophorous vacuole into the host cell cytoplasm where they localize to peculiar structures called Maurer’s clefts. We are currently elucidating their transport, their function, and their cooperation or interaction with other proteins. Already, we were able to show by knock out experiments that the elimination of one of these proteins resulted in the complete loss of the major virulence determinant PfEMP1 on the surface of the infected erythrocytes. PfEMP1 is essential for parasite survival in the host, but is also responsible for most of the pathology observed with malaria. Hence, blocking its transfer from the parasite to the erythrocyte surface would eliminate to a large degree the associated pathology and would probably reduce parasite survival in the host significantly. Hence, our studies on associated proteins facilitating the transport of this variable surface antigen might pave the way for new and innovative interventions by blocking the transfer of such essential molecules and possibly rendering the parasite to an avirulent pathogen.

 

We are currently analysing the second histidine rich protein for its localization, but placing most emphasis on its interaction with other proteins to understand its function as probable transport molecule (chaperon) for cargo into the Maurer’s clefts.

 

Hans-Peter Beck