The clinical symptoms of malaria arise from cycles of parasite replication in the blood. This requires egress (exit) of mature parasites from their host erythrocyte, during which the parasites break down their enclosing vacuole and erythrocyte host membranes. The abundant parasite surface protein MSP1 plays a key role in egress. This project focuses on the cascade of events leading to membrane permeabilisation and rupture. The student will generate conditional mutants of MSP1 using genetic manipulation and optical microscopy of malaria parasites, then use cryo electron microscopy and tomography to examine the molecular and cellular mechanisms of membrane disruption.
Thomas, JA, Tan, MSY, Bisson, C, Borg, A, Umrekar, TR, Hackett, F, Hale, VL, Vizcay-Barrena, G, Fleck, RA, Snijders, AP, Saibil, HR and Blackman, MJ. (2018) A protease cascade regulates release of the human malaria parasite Plasmodium falciparum from host red blood cells. Nature Microbiol. 3, 447-455.
Hale, VL, Watermeyer, JM, Hackett, F, Vizcay-Barrena, G, van Ooij, C, Thomas, JA, Spink, MC, Harkiolaki, M, Duke, E, Fleck, RA, Blackman, MJ & Saibil, HR (2017) Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse in Plasmodium falciparum egress. PNAS 114, 3439-3444.
Watermeyer, JM, Hale, VL, Hackett, F, Clare, DK, Cutts, EE, Vakonakis, I, Fleck, RA, Blackman, MJ & Saibil, HR (2016) A spiral scaffold underlies cytoadherent knobs in Plasmodium falciparum-infected erythrocytes. Blood 127, 343-351.
Das S, Hertrich N, Perrin AJ, Withers-Martinez C, Collins CR, Jones ML, Watermeyer JM, Fobes ET, Martin SR, Saibil HR, Wright GJ, Treeck M, Epp C, Blackman, MJ (2015) Processing of plasmodium falciparum merozoite surface protein msp1 activates a spectrin-binding function enabling parasite egress from RBCs. Cell Host Microbe 18, 433-444.