We are interested in understanding the biology of the deadly human malaria parasite, Plasmodium falciparum. We deploy a wide variety of tools to study the parasite including cellular biology, chemical biology, molecular biology and biochemistry. We also develop tools to help us probe the function of genes in parasite biology. One such tool that we use extensively are the degradation domains that are used to knockdown protein function.
The malaria parasite lives within human red blood cells. Our current focus is on understanding the roles of a family of proteins called chaperones or heat shock proteins (Hsp) in parasite biology. All living cells have this specialized family of proteins, such as Hsp110, Hsp70 and Hsp40, that use ingenious mechanisms to maintain cellular proteostasis, and usher proteins to their proper cellular destinations across cellular membranes.
For its growth within human erythrocytes, P. falciparum has to modify this terminally differentiated human cell to establish a suitable niche. The parasite does this via a sophisticated protein export pathway that transports proteins encoded by the parasite genome through at least three membranes into the erythrocyte cytoplasm and cell membrane. Exported proteins usually (but not always) contain a targeting motif (PEXEL or VTS) that binds PI3P and is cleaved by an ER-resident aspartic protease, Plasmepsin V. The cleaved proteins are then secreted to a distinct compartment, the parasitophorous vacuole (PV) and a protein translocon residing in the PV membrane exports proteins in the host cell. Several parasite proteins populate the PV but are not exported and the parasite also transports proteins to specialized organelles such as the apicoplast (a chloroplast-like organelle required for isoprenoid synthesis). Given the existence of several protein transport pathways in parallel, all of which require several chaperones, we are interested in answering the question: What is the role of chaperones in the ensuring precise and accurate transport of proteins to the various compartments in the P. falciparum infected red blood cell?