DFG project: The assembly of multimeric protein complexes in the sexual stages of the human malaria parasite

 

Duration: 3 years

Application period: 2012-2016

Doctorate: Dr. Andreas Edler von Bohl

Summary:

Sexual reproduction of the malaria parasite is initiated following its transmission from the human host to the mosquito vector during a blood meal. The sexual stages are the only life-cycle stages of the parasite that are able to establish an infection in the mosquito and thus play an important role for spread of the tropical disease. Parasite transmission is mediated by sexual precursor cells, the gametocytes, that in the midgut of the mosquito transform into fertile gametes. During gametocyte differentiation, a high number of surface-associated adhesion proteins are expressed, which assemble to multimeric protein complexes (MPCs) and which are subsequently exposed on the gamete surface. Antibodies directed against MPC proteins result in complement-mediated lysis of sexual stage parasites in the mosquito midgut, thereby blocking further development of the parasite in the vector. MPC proteins therefore represent promising candidates for transmission blocking vaccines. MPCs are multifunctional units mediating contact of sexual stage parasites and possibly play a role in gametogenesis as well as in finding and fusion of mating partners. The assembly of MPCs and their fate during parasite development in the mosquito midgut, however, are up to date not well understood.The project thus aimed at investigating the molecular composition of sexual stage MPCs, identifying a possible connection of MPCs with the submembranous elements of the gametocyte cytoskeleton and studying processing, relocation and degradation of MPC proteins.