We are interested in the cell and molecular biology of protozoan parasites. Most of our work is focused on members of the phylum Apicomplexa. Organisms in this group cause a number of important diseases including malaria, severe opportunistic infections associated with AIDS, and fetal and early childhood diseases. We use a broad array of modern genomic, genetic, cell biological and biochemical approaches to understand fundamental parasite biology and use this knowledge to identify and develop targets for intervention. Currently we are focusing on the following specific areas:
The function and cell biology of the parasite chloroplast.
Apicomplexan parasites harbor a remnant chloroplast (the apicoplast) that they obtained through secondary endosymbiosis. This organelle is essential for parasite growth and as human cells lack chloroplasts offers a unique opportunity for anti-parasitic drug development. Using Toxoplasma gondii as a robust genetic model we are characterizing the specific metabolic functions of the organelle to pinpoint which pathway(s) would be most suitable as a drug target. The apicoplast also provides a tractable model to study the cell biology of endosymbiosis. What is the cellular machinery that builds, maintains and replicates an organelle that formed through the merger of three previously independent organisms (one prokaryotes and two eukaryotes)? Our current work uses a mix of genomics and genetics to mechanistically dissect apicoplast biogenesis, protein import and division.
The biology of cryptosporidiosis
Cryptosporidium is one of the most important causes of diarrheal disease in infant and toddlers and a leading contributor to early childhood mortality. Neither vaccines nor fully effective drugs are available for this disease. Research on this pathogen has long been stalled by its poor experimental tractability. Recently we developed transfection and a powerful genetic modification system for Cryptosporidium. We are using these new tools to disect the intereaction between the parasite and its host. Cryptosporidium has a unique single host life cycle that combine asexual and sexual processes. These processess unfold and can be studied in a simple mouse model over the course of a week. Sexual recombination also offers exciting opportunities for forward genetic analysis using genetic crosses. We also develop and use genetic approaches to support the discovery of new treatments for cryptosporidiosis and to understand their mechanims of action.
Find a complete listing of publications at pubmed
Sheiner, L., Fellows, J.D., Brooks, C.F., Agrawal, S., Holmes, Z.C., Bietz, I., Flinner, N., Heiny, S., Mirus, O., Przyborski, J.M. and Striepen, B. (2015) Toxoplasma gondii Toc75 functions in import of luminal but not peripheral apicoplast proteins. Traffic. In press.
Vinayak, S.*, Pawlowic, M.C.*, Sateriale, A*, Brooks, C.F., Studstill, J.C., Bar-Peled, Y., Cirpriano, M.J. and Striepen, B. (2015) Genetic modification of the diarrheal pathogen Cryptosporidium parvum. Nature 523: 477–480 (*equal contribution).
Suvorova, E.S., Francia, M.E., Striepen, B., and White, M.W. (2015) A novel bipartite centrosome coordinates the apicomplexan cell cycle. PLoS Biology 13:e1002093.
Vinayak, S., Brooks, C., Naumov, A. Suvorova, E.S., White, M.W., and Striepen, B. (2014) A fosmid-based recombinieering platform for genetic engineering in Toxoplasma gondii. mBio: 02021-14.
Francia, M.E., and Striepen B. (2013) Cell division of apicomplexan parasites, Nature Reviews Microbiology 12:125-136.
Striepen B. (2013) Time to tackle cryptosporidiosis. Nature 503: 189-191.
van Dooren, G.G. and Striepen B. (2013) The algal past and parasite present of the apicoplast. Annu Rev. Microbiol, 67: 271–289.
Agrawal S, Chung DW, Ponts N, van Dooren GG, Prudhomme J, Brooks CF, Rodrigues EM, Tan JC, Ferdig MT, Striepen B, Le Roch KG (2013) An Apicoplast Localized Ubiquitylation System Is Required for the Import of Nuclear-encoded Plastid Proteins. PLoS Pathog. 9(6):e1003426.
Francia, M.E., Jordan, C.N., Patel, J., Sheiner, L., Demerely, J.L., Fellows, J.D., deLeon, J., Morrissette, N.S., Dubremetz, J.F., and Striepen, B. (2012) Cell division in apicomplexan parasites is organized by a homolog of the striated rootlet fiber of algal flagella. PLoS Biol., 10(12):e1001444.
MacRae, J.I, Sheiner, L, Naid, A., Tonkin, C., Striepen, B., and McConville, M.J. (2011) A GABA shunt and TCA cycle have important roles in the energy metabolism of intra- and extracellular Toxoplasma gondii stages. Cell Host & Microbe 12(5):682-92. (joint first and senior authors)
Reiff, S.B., Vaishnava, S., and Striepen, B. (2012) The Hu protein of Toxoplasma gondii is important for apicoplast genome stability and inheritance. Eukayot. Cell. 11: 905-915
Ramarkrishnan, S., Docampo, M.D., Macrae, J.I., Pujol, F., Brooks, C.F., van Dooren, G.G., Hiltunen, J.K., Kastaniatos, A, McConville, M.J., and Striepen, B. (2012) The apicoplast and endoplasmic reticulum cooperate in fatty acid biosynthesis in the apicomplexan parasite Toxoplasma gondii, J. Biol. Chem. 287:4957-4971
Sheiner, L., Demerely, J., Poulson, S., Michael Benke, White, Michael and Striepen, B. (2011) A systematic screen to discovery and analyze apicoplast proteins identifies a conserved and essential protein import factor. PLoS Pathogens 7: e1002392.
Striepen, B. (2011) The apicoplast: a red alga in human parasites. Essays in Biochem. 24:111-25
Nair, S.C. and Striepen, B. (2011) What do human parasites do with a chloroplast anyway? PLoS Biology 9:e1001137.
Nair, S.C., Brooks, C.F., Goodman, C.D, Sturm, A., McFadden,G.I., Sndriyal, S., Anglin, J.L, Song, Y., Moreno, N.J., and Striepen, B. (2011) Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma. J. Exp. Med. 208: 1547-1559.
Brooks, C.F., Francia, M.E., Gissot, M., Kroken, M.M., Kim, K., and Striepen B. (2011) Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle. Proc. Natl. Acad. Sci. U.S.A. 108: 3767-3772.
Sharling, L, Liu, X., Gollapalli D.R., Maurya S. K. Hedstrom, L., Striepen, B. (2010) A screening pipeline for antiparasitic agents targeting Cryptosporidium inosine monophosphate dehydrogenase. PLoS Negl. Trop. Dis. 10: e794.
Sun, X., Sharling, L., Mudeppa, D.G., Pankiewicz, K., Rathod, P.K., Mead, J., Striepen, B., and Hedstrom, L. (2010) Prodrug activation by Cryptosporidium Thymidine Kinase. J. Biol. Chem, 285:15916-15922.
Brooks, C.F., Johnsen, H., van Dooren, G.G., Muthalagi, M., Liu, S.S., Bohne, W., Fischer, K., Striepen B. (2010) The Toxoplasma Apicoplast Phosphate Translocator Links Cytosolic and Apicoplast Metabolism and Is Essential for Parasite Survival. Cell Host & Microbe: 7(1):62-73.