BORIS STRIEPEN
Associate Professor
Ph.D., 1995
Philipps-Universität, Marburg, Germany
RESEARCH
The lab has a broad interest in the molecular basis of intracellular parasitism—how can one cell live within and on the expense of another cell. The parasite has to master a complex set of tasks to do so: invasion of the host-cell, establishment of an environment suitable for replication, avoidance of counter measures by the host and finally initiation of a new round of infection and replication. We believe that studying these processes will lead to the discovery of exciting parasite specific molecular adaptations and mechanisms. Studying the interface of intracellular pathogen and host cell can also be a valuable source for new insights into the basic cell biology of mammalian cells. Furthermore, studying key events of the parasites replication cycle and pathogenesis might lead to novel targets for anti-parasitic action.
The parasitic organism we use in our research is Toxoplasma gondii, a relative of Plasmodium, the causative agent of Malaria. T. gondii is a widely distributed parasite of humans and animals (15-30% of the US to over 70% of the European adult population is infected). Usually the infection is benign, and the parasite is very safe to handle in the laboratory. But under certain conditions, it can cause congenital infection of the fetus during pregnancy and severe encephalitis in patients suffering from immunodeficiency. Sadly Toxoplasma encephalitis is one of the leading causes of death among AIDS patients.
Toxoplasma is very amendable to genetic experiments. We can
generate transgenic parasites—both transient and stable, target and knock
out genes by homologous recombination, use insertional mutagenesis and tagging,
and exploit a large number of versatile selectable markers and reporter genes.
This molecular toolbox has been the key to developing Toxoplasma into a powerful
genetic model system—especially with an eye on Malaria. We are exploiting
novel fluorescent markers, to localize proteins at the subcellular level,
to analyze dynamic events by time lapse video microscopy and to build genetic
screens.
Host-cell invasion and the modification of the initial parasitophorous vacuole into a compartment suitable for parasite survival and replication is tightly associated with secretion from three sets of parasite specific organelles (rhoptries, micronemes and dense granules). Currently we are focussing our studies on the parasite's secretion and sorting machinery to dissect the relationship between secretion and invasion. We are using reverse genetics and high resolution deconvolution imaging in living cells to map sequences responsible for proper targeting of secretory proteins within the parasite and the host cell. In a second project addressing protein targeting we are using an approach analogous to transposon mutagenesis, randomly introducing GFP into the genome. We are subsequently isolating tagged mutants with interesting localization phenotypes by FACS and high throughput microscopy. Forward genetics is where we would like to go. We are building genetic screens based on FACS and automated visual analysis to isolate conditional mutant parasites failing to secrete or properly target their secretory proteins. Such mutants will be exciting tools to study the biological role of secretion and to identify key genes by genetic complementation.
Dr. Striepen is a member of the Center for Tropical and Emerging Global Diseases .
| CONTACT INFORMATION |
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(706) 583-0588, striepen@cb.uga.edu
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| SEE ALSO |
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Striepen Lab Page
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| Carly Jordan | |
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| Sethu Nair | |
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| Sarah Reiff | |
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REPRESENTATIVE PUBLICATIONS
PubMed listing of all publications by Boris Striepen
Striepen, B., Jordan, C.N., Reiff, S. and van Dooren, G.G. (2007) Building the perfect parasite: apicomplexan cell division. PLoS Pathogens 3: e78
Mazumdar, J., Wilson, E., Masek, K., Hunter, C and Striepen, B (2006) Apicoplast fatty acid synthesis is essential for organelle biogenesis and survival in Toxoplasma gondii. Proc. Natl. Acad. Sci. 103:13192-13197.
Vaishnava, S. and Striepen, B. (2006) The cell biology of endosymbiosis - How parasites build, divide and segregate the apicoplast. Mol. Microbiol. 61: 1380-1387
Gubbels, M.J., Vaishnava, S., Boot, N., Dubremetz, J.F. and Striepen, B., (2006) A MORN-repeat protein is a dynamic component of the Toxoplasma gondii cell division apparatus. J. Cell Sci. 119, 2236-2245.
Vaishnava, S., Morrison, D., Gaji, R.Y., Entzeroth, R.K., Howe, D.L., and Striepen, B. (2005) Development and segregation of the plastid in the apicomplexan parasite Sarcocystis neurona. J. Cell Sci. 118: 3397-3407.
Gubbels, M.J., Striepen, B., Shastri, N., Turkoz, M., and Robey, E.A. (2005) Class I MHC presentation of antigens secreted into the parasitophorous vacuole by Toxoplasma gondii. Infect. Immun. 73: 703-11.
White, M.W., Jerome, M. E., Vaishnava, S., Guerini M., Behnke, M. and Striepen, B. (2005) Studies of a mitotic mutant yield evidence for cell cycle coordination in Toxoplasma gondii. Mol. Microbiol. 55: 1060-71.
Umejiego, N.N., Riera, T., Li, C., Hedstrom, L., and Striepen, B. (2004) Cryptosporidium parvum IMP dehydrogenase: Identification of functional, structural and dynamic properties that can be exploited for drug design. J. Biol. Chem. 279: 40320-40327.
Striepen, B. and Kissinger, J.C. (2004) Genomics meets trangenics in the search for the elusive Cryptosporidium drug target. Trends Parasitol. 20: 355-358
Striepen, B., Pruijssers, J.P., Huang, Li, C., Gubbels, M.J., Umejiego, N.N., Hedstrom, L, and Kissinger, J.C (2004) Genetransfer in the evolution of parasite nucleotide biosynthesis. Proc. Natl. Acad. Sci. USA. 101:3154-3159.
Gubbels, M.J., and Striepen, B. (2004) Studying the cell biology of apicomplexan parasites using fluorescent proteins. Microscop. Microanal. 10: 568-579.Gubbels, M.J., Wieffer, M., and Striepen, B. (2004) Fluorescent protein tagging in Toxoplasma gondii: identification of a novel inner membrane complex component conserved among Apicomplexa. Mol. Biochem. Parasitol. 137: 99-110.
Gubbels, M.J., Li, C., and Striepen, B. (2003) High throughput growth assay for Toxoplasma gondii using yellow fluorescent protein, Antimicrob. Agents Chemother. 47: 309-316.
Striepen, B., White, M.W., Li, C., Guerrini, M., Malik, S.B., Logsdon, J.M., Liu, C., Abrahamsen, M.S. (2002) Genetic complementation in apicomplexan parasites. Proc. Natl. Acad. Sci. USA 99: 6304-6309.
Striepen, B., Crawford, M.J. Shaw, M.K., Tilney, L.D., Seeber, F., and Roos, D.S. (2000) The plastid of Toxoplasma gondii is divided by association with the centrosomes, J. Cell Biol. 151: 1423-1434.