Molekulare Grundlage der Biogenese der Parasitophoren Vakuole von Plasmodium falciparum

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Apicomplexa are eukaryotic unicellular organisms and obligatory intracellular parasites, the medically most relevant of which is Plasmodium falciparum. Upon invasion into human erythrocytes, Plasmodium initiates the formation of a membrane which creates a unique compartment, the parasitophorous vacuole, in which the parasite resides inside the host cell. Proteins discharged from apical secretory organelles, e.g. the rhoptries, are presumably involved in the biogenesis and maintenance of the parasitophorous vacuole membrane (PVM). Despite the pivotal role of the PVM for the parasite´s intracellular life, most of the protein components of the PVM have not been molecularly and functionally characterized. The major issue of the proposed project is the analysis of the molecular repertoire of isolated PVM by a cell-map proteomic approach using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) combined with mass spectrometry. Data from peptide mass finger prints linked to the genome project of P. falciparum will allow to identify key components of the PVM mediating functions vital for the parasite such as transport of nutrients into the vacuole and export of host cell modulating components. Kinetic studies analyzing the proteins of the PVM between plasmodial invasion into and evasion from the red blood cell, recombinant expression of selected proteins for functional studies and their immunolocalization to the synthesizing organelles will help to elucidate the biological role of the vacuolar membrane.