Ph.D., Utrecht University, the Netherlands
Tel: (617) 552-8722
E-mail: marcjan.gubbels.1@bc.edu
Dr. Gubbels's Website
Field of Interest
Genetic approaches towards the cell biology of Toxoplasma gondii
Academic Profile
The protozoan parasite Toxoplasma gondii is a member of the phylum Apicomplexa and can cause severe disease in humans. This parasite is easily grown and manipulated in vitro and has in recent years developed as a safe and versatile model for other apicomplexan parasites (e.g. malaria). We are using and developing forward, reverse and functional genetic tools using enzymatic as well as fluorescent protein reporter assays in combination with cell sorting and fluorescence microscopy to learn more about the parasite’s cell biology.
Parasite replication is conserved, yet are variations on a theme in different apicomplexan parasites. Toxoplasma divides by an internal budding process called endodyogeny where two daughters are being assembled inside the mother, which is significantly different from mammalian cell division. The parasite’s cytoskeleton, consisting of microtubules as well as a membrane skeleton in combination with intermediate protein filaments (the inner membrane complex or IMC) serves as a scaffold for daughter assembly. Recently we identified several components that act in the cytoskeleton assembly as well as daughter formation which are currently being characterized in detail.
Host cell invasion is an essential step in the life cycle of Apicomplexa and identifying essential steps and/or molecules in the process would provide attractive potential therapeutic targets. To identify key molecules in invasion, a set of conditional parasite invasion mutants has been generated through chemical as well as insertional (conditional) mutagenesis. Mutants are being analyzed through a set of cell biological assays while at the same time the mutated genes are being identified using cosmid library complementations as well as plasmid rescues.
In addition, we are interested in the DNA damage repair pathways in Toxoplasma. In particular, the high rate of non-homologous end joining over homologous recombination in case of double strand breaks. By better understanding this balance we hope to enhance the efficiency of homologous recombination facilitating more efficient gene knock-outs and allelic replacements and as such enhancing the genetic accessibility of the parasite even further.
Representative publications
Frickel, E.M., Sahoo, N., Hopp, J., Gubbels, M.-J., Craver, M.P., Knoll, L.J., Ploegh, H., and Grotebreg, G. 2008. Parasite stage-specific recognition of endogenous Toxoplasma gondii epitopes by CD8+T cells. The Journal of Infectious Diseases. (In Press).
Gubbels, M.-J., White, M., and Szatanek, T. 2008. The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched? International Journal for Parasitology 38: 1343–1358. (Invited Review). (link to PubMed abstract)
Muskavitch, M., Barteneva, N., and Gubbels, M.-J. 2008. Chemogenomics and parasitology: small molecules and cell-based assays to study infectious processes. Combinatorial Chemistry & High Throughput Screening 11: 629–649. (Invited Review). (link to PubMed abstract)
Ferguson, D.J.P., Sahoo, N., Pinches, R.A., Bumstead, J.M., Tomley, F.M., and Gubbels, M.-J. 2008. MORN1 has a conserved role in asexual and sexual development across the Apicomplexa. Eukaryotic Cell 7: 698-711. (Featured in ASM Microbe, June 2008). (link to PubMed abstract)
Gubbels, M.-J., Brooks, C.F., Muthalagi, M., Szatanek, T., Flynn, J., Parrot, B., Striepen, B., and White, M.W. 2008. Forward genetic analysis of the apicomplexan cell and division cycle in Toxoplasma gondii. PLoS Pathogens 4(2): e36 (0001–0015). (Editor’s Pick).
Frickel, E.-M., Quesada, V., Muething, L., Gubbels, M.-J., Spooner, E., Ploegh, H., and Artavanis-Tsakonas, K. 2007. UCHL3 retains dual specificity for ubiquitin and Nedd8 throughout evolution. Cellular Microbiology 6: 1601-1610. (link to PubMed abstract)
Andrade, R.M., Wessendarp, M., Gubbels, M.-J., Striepen, B., and Subauste, C.S. 2006. CD40 induces macrophage anti-microbial activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes. The Journal of Clinical Investigation 116: 2366–77. (link to PubMed abstract)
Dalton, J.A., Cruickshank, S.M., Egan, C.E., Mears, R., Newton, D.J., Andrew, E.M., Lawrence, B., Howell, G., Else, K.J., Gubbels, M.-J., Striepen, B., Smith, J., White, S.J, and Carding, S.R. 2006. Intraepithelial gamma-delta positive lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 131: 818–29. (link to PubMed abstract)
Gubbels, M.J., Mazumdar, J., van Dooren, G., and Striepen, B. 2006. Manipulating the Toxoplasma genome. In "The biology of Toxoplasma gondii." D. Soldati and J. Ajioka (eds.). Horizon Scientific Pres, Norwich, UK. (Link to Publisher)
Gubbels, M.-J., Vaishnava, S., Boot, N., Dubremetz, J.-F., and Striepen, B. 2006. A MORN-repeat protein is a dynamic component of the cell division apparatus of the parasite Toxoplasma gondii. Journal of Cell Science 119: 2236–2245. (link to PubMed abstract)
Egan, C.E., Dalton, J.E., Andrew, E.M., Smith, J.E., Gubbels, M.-J., Striepen, B., and Carding, S.R. 2005. A requirement for the Vgamma1+ subset of peripheral gamma-delta T cells in the control of the systemic growth of Toxoplasma gondii and infection-induced pathology. The Journal of Immunology 175: 8191–8199. (link to PubMed abstract)
Gubbels, M.-J., Striepen, B., Shastri, N., Turkoz, M., and Robey, E. 2005. Class I MHC presentation of antigens that escape from the parasitophorous vacuole of Toxoplasma gondii. Infection and Immunity 73: 703–711. (link to PubMed abstract)
Howe, D.K., Gaji, R.Y., Mroz-Barrett, M., Gubbels, M.-J., Striepen, B., and Stamper, S. 2005. Sarcocystis neurona merozoites express a family of immunogenic surface antigens that are orthologues of the SAG/SRS surface antigens in Toxoplasma gondii. Infection and Immunity 73: 1023–1033. (link to PubMed abstract)
Gubbels, M.-J., and Striepen, B. 2004. Fluorescent proteins as tools to study the cell biology of protozoan parasites. (Review). Microscopy and Microanalysis 10: 1–12. (link to PubMed abstract)
Gubbels, M.-J., Wieffer, M., and Striepen, B. 2004. Fluorescent protein tagging in Toxoplasma gondii: identification of novel inner membrane complex component conserved in Apicomplexa. Molecular and Biochemical Parasitolology 137: 99–110. (link to PubMed abstract)
Radke, J., Gubbels, M.-J., Striepen, B., and White, M. 2004. Identification of a sporozoite-specific member of the Toxoplasma SAG superfamily via genetic complementation. Molecular Microbiology 52: 93–105. (link to PubMed abstract)
Striepen, B., Pruijssers, A.J.P., Huang, J., Li, C., Gubbels, M.-J., Umejiego, N.N., Hedstrom, L., and Kissinger, J.C. 2004. Gene transfer in the evolution of parasite nucleotide biosynthesis. Proceedings of the National Academy of Sciences USA 101: 3154–3159. (link to PubMed abstract)
Gubbels, M.-J., Li, C., and Striepen, B. 2003. High throughput growth assay for Toxoplasma gondii using yellow fluorescent protein. Antimicrobial Agents and Chemotherapy 47: 309–316. (link to PubMed abstract)
Gubbels, M.-J., Katzer, F., Shiels, B.R., and Jongejan, F. 2001. Study of Theileria annulata population structure during bovine infection and following transmission to ticks. Parasitology 123: 553–561. (link to PubMed abstract)
Gubbels, M.-J., Katzer, F., Hide, G., Jongejan, F., and Shiels, B.R. 2000. Generation of a mosaic pattern of diversity in the major merozoite-piroplasm surface antigen of Theileria annulata. Molecular and Biochemical Parasitology. 110: 23–32. (link to PubMed abstract)
Gubbels, M.-J., Yin, H., van der Weide, M., Bai, Q., Nijman, I.J., Liu, G., and Jongejan, F. 2000. Molecular and biological characterization of the Theileria buffeli/orientalis group. International Journal for Parasitology 30: 943–952. (link to PubMed abstract)
Gubbels, J.M., de Vos, A.P., van der Weide, M., Viseras, J., de Vries, E., Schouls, L.M., and Jongejan, F. 1999. Simultaneous detection of bovine Theileria and Babesia species using reverse line blot hybridization. Journal of Clinical Microbiology 37: 1782–1789. (link to PubMed abstract)
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