Functional Characterization of Plasmodium Liver Stage Proteins at the Parasite/Host Interface

• Applicant: Professor Dr. Kai Matuschewski
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2004 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5434993

During malaria transmission Plasmodium sporozoites actively enter the liver and transform into clinically silent liver stages (LS). Each individual LS undergoes multiple rounds of nuclear divisions and eventually produces thousands of first-generation merozoites that initiate the erythrocytic cycle causing malaria pathology. Liver stages are ideal targets for causal prophylactic drugs and vaccine strategies. However, only very limited information is available on the molecular make-up of these stages, and LS can be considered the terra incognita of the malarial life cycle. LS reside within an organelle of its own making, the parasitophorous vacuole. We recently identified a family of small secretory proteins that localize to this border between the parasite and the hepatocyte cytosol. Targeted gene disruption of one family member resulted in arrest of late LS development. We suggest to systematically employ reverse genetics as well as cell biological techniques to study the role of these Plasmodium proteins during LS development. Generation of attenuated Plasmodium liver stage parasites will be fundamental in understanding the biology of the parasite`s life within the hepatocyte.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1131: Life Inside Cells