Sean Prigge, PhD, is a structural biologist and parasitologist who studies essential nutrients and metabolic pathways in malaria parasites.
malaria; apicoplast; enzymology; mitochondrion; vitamins; metabolism; transcriptomics; metabolomics; enzyme cofactors; genome editing
Experiences & Accomplishments
Johns Hopkins School of Medicine
Malaria, a disease caused by protozoan parasites, is one of the most dangerous infectious diseases, claiming millions of lives and infecting hundreds of millions of people annually. Malaria parasites contain an essential organelle called the apicoplast that is thought to have arisen through endosymbiosis of an algal cell which had previously incorporated a cyanobacterium. Due to its prokaryotic origin, the apicoplast contains a range of metabolic pathways that differ significantly from those of the human host. We are investigating biochemical pathways found in the apicoplast, particularly those required for the biosynthesis and modification of fatty acids. This metabolism should require several enzyme cofactors such as pantothenate, lipoic acid, biotin and iron-sulfur clusters. We are interested in these cofactors, how they are acquired, how they are used, and whether they are essential for the growth of blood stage malaria parasites. We approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.
- Russell P Swift, Krithika Rajaram, Hans B Liu, and Sean T Prigge, Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption. EMBO J, 40, e107247 (2021).
- Russell P Swift, Krithika Rajaram, Cyrianne Keutcha, Hans B Liu, Bobby Kwan, Amanda Dziedzic, Anne E Jedlicka, and Sean T Prigge. The NTP generating activity of pyruvate kinase II is critical for apicoplast maintenance in Plasmodium falciparum. Elife, 9, e50807 (2020).
- Russell P Swift, Krithika Rajaram, Hans B Liu, Amanda Dziedzic, Anne E Jedlicka, Aleah D Roberts, Krista A Matthews, Hugo Jhun, Namandje N Bumpus, Shivendra G Tewari, Anders Wallqvist, and Sean T Prigge. A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites. PLoS Pathog, 16, e1008316 (2020).
- Aleah D Roberts, Sethu C Nair, Alfredo J Guerra, and Sean T Prigge. Development of a conditional localization approach to control secretory protein trafficking in malaria parasites. Traffic, 20, 571-582 (2019).
- Teegan A Dellibovi-Ragheb, Hugo Jhun, Christopher D Goodman, Maroya S Walters, Daniel R T Ragheb, Krista A Matthews, Krithika Rajaram, Satish Mishra, Geoffrey I McFadden, Photini Sinnis, and Sean T Prigge. Host biotin is required for liver stage development in malaria parasites. Proc Natl Acad Sci U S A, 115, E2604-E2613 (2018).
Roles of Lipoate Pathways in Plasmodium Survival
Determinants of apicoplast maintenance in malaria parasites
Characterization of stress responses in malaria parasites to inform a computational model of parasite metabolism.