Sean T. Prigge, PhD
Center & Institute Affiliation(s):
615 N. Wolfe Street, E4628
Baltimore , Maryland 21205
PhD , Johns Hopkins University , 1997
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.
Molecular Microbiology and Immunology, malaria, fatty acid biosynthesis, apicoplast, x-ray crystallography, enzymology
G. A. Afanador, S. P. Muench, M. McPhillie, A. Fomovska, A. Schon, Y. Zhou, G. Cheng, J. Stec, J. S. Freundlich, H. M. Shieh, J. W. Anderson, D. P. Jacobus, D. A. Fidock, A. P. Kozikowski, C. W. Fishwick, D. W. Rice, E. Freire, R. McLeod and S. T. Prigge, Discrimination of Potent Inhibitors of Toxoplasma gondii Enoyl-Acyl Carrier Protein Reductase by a Thermal Shift Assay. Biochemistry 52: 9155-9166 (2013).
J. E. Gisselberg, T. A. Delli-Bovi, G. Bosch, and S. T. Prigge. The Suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. PLoS Pathogens, 9(9):e1003655 (2013).
B. Falkard, L. S. Hecht, K. A. Mathews, P. P. Henrich, S. Gulati, R. E. Lewis, M. J. Manary, E. A. Winzeler, P. Sinnis, S. T. Prigge, V. Heussler, C. Deschermeier, and D. A. Fidock. A Key Role for Lipoic Acid Synthesis During Plasmodium Liver-Stage Development. Cellular Microbiology, 15, 1585-1604 (2013).
J. R. Gallagher, K. A. Matthews, S. T. Prigge, Plasmodium falciparum apicoplast transit peptides are unstructured in vitro and during apicoplast import. Traffic, 12, 1124-1138 (2011).
J. R. Gallagher, S. T. Prigge, Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked and reduced states and their prevalence during blood stage growth. Proteins 78, 575-588 (2010).