Malaria parasites contain an essential organelle called the apicoplast, which is thought to have stemmed from endosymbiosis of an algal cell, which previously incorporated a cyanobacterium. Due to its prokaryotic origin, the apicoplast contains a range of metabolic pathways that greatly differ from those of the human host. Dr. Prigge’s lab is 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. Their focus is on these cofactors, how they are acquired, how they are used and whether they are essential for the growth of blood stage malaria parasites. Dr. Prigge and his team approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.
Lab Website: Sean Prigge Laboratory
Afanador GA, Matthews KA, Bartee D, Gisselberg JE, Walters MS, Freel Meyers CL, Prigge ST. “Redox dependent lipoylation of mitochondrial proteins in Plasmodium falciparum.” Mol Micro. 2014;94: 156-171.
Gisselberg JE, Dellibovi-Ragheb TA, Matthews KA, Bosch G, Prigge ST. “The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites.” PLoS Pathog. 2013;9: e1003655.
Afanador GA, Muench SP, McPhillie M, Fomovska A, Schon A, Zhou Y, Cheng G, Stec J, Freundlich JS, Shieh HM, Anderson JW, Jacobus DP, Fidock DA, Kozikowski AP, Fishwick CW, Rice DW, Freire E, McLeod R, Prigge ST. “Discrimination of potent inhibitors of toxoplasma gondii enoyl-acyl carrier protein reductase by a thermal shift assay.” Biochemistry. 2013;52:9155-66.
Gallagher JR, Matthews KA, Prigge ST. “Plasmodium falciparum apicoplast transit peptides are unstructured in vitro and during apicoplast import.” Traffic. 2011;12:1124-1138.
GallagherJR, Prigge ST. “Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked and reduced states and their prevalence during blood stage growth.” Proteins. 2010;78:575-588.