Sean Prigge
Metabolic pathways in malaria parasites
Professor
Department of Molecular Microbiology and Immunology
Bloomberg School of Public Health
Research Overview
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 or liver stage malaria parasites. We approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.
Selected Publications
- Swift RP, Elahi R, Rajaram K, Liu HB, Prigge ST. The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification. eLife, 2023.
- Nair SC, Munro JT, Mann A, Llinás M, Prigge ST. The mitochondrion of Plasmodium falciparum is required for cellular acetyl-CoA metabolism and protein acetylation. PNAS, 2023.
- Rajaram K, Tewari SG, Wallqvist A, Prigge ST, Metabolic changes accompanying the loss of fumarate hydratase and malate-quinone oxidoreductase in the asexual blood stage of Plasmodium falciparum. J Biol Chem, 2022.
- Swift RP, Rajaram K, Liu HB, Prigge ST. Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption. EMBO Journal, 2021.
- Swift RP, Rajaram K, Keutcha C, Liu HB, Kwan B, Dziedzic A, Jedlicka AE, Prigge ST. The NTP generating activity of pyruvate kinase II is critical for apicoplast maintenance in plasmodium falciparum. eLife, 2020.