Functional characterization of the main integral protein components of the parasite-host cell interface of Plasmodium falciparum blood stages

• Applicant: Dr. Tobias Spielmann
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 404870441

The intracellular development of the human malaria parasite Plasmodium falciparum in red blood cells is responsible for the clinical symptoms of malaria. In the red blood cell, the parasite is separated from the host cell cytosol by a membrane called the parasitophorous vacuolar membrane (PVM). This membrane plays a key role in the interaction of the parasite with its host cell but many of its functions are poorly understood or unknown. The PVM contains short, highly charged and highly abundant integral membrane proteins termed EXP1 and ETRAMPs (a family of 14 proteins). These molecules are the only so far known proteins bridging this membrane (they contain a domain reaching into the host cell and one facing the parasite). Several, including EXP1, are indicated to be essential for parasite survival and they likely play critical roles in the interaction of the parasite with the host cell. However, due to technical limitations, they have so far not been functionally analysed in P. falciparum parasites. Using new technology we generated a conditional knock out of EXP1. Here we propose to use this to study EXP1 and use the same technology to functionally analyse ETRAMPs. In addition we developed a new modified proximity biotinylation method to identify interaction partners and compartment proteomes that we propose to use to identify factors interacting with the host cell facing domain of EXP1 and ETRAMPs. This will also generate a proteome of the outer face of the PVM that with other means is difficult to obtain. We expect this work to unravel the function of the major integral components of the parasite host cell interface and to contribute to an understanding how the parasite exploits and interacts with the host red blood cell.

• DFG Programme: Research Grants