Biology Department Faculty
Marc-Jan Gubbels
Professor
Marc-Jan Gubbels
Ph.D.
Contact
Higgins Hall 428
Telephone: 617-552-8722
Email: marcjan.gubbels@bc.edu
ORCID 0000-0002-2769-8600
Education
- B.S., Wageniningen University, the Netherlands
- M.S., Wageniningen University, the Netherlands
- Ph.D., Utrecht University
Research Interests
Genetic approaches towards the cell biology of Toxoplasma gondii.
Department
Research
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.
Selected Publications
- Lou, J., Y. Rezvani, A. Argenis, D. Degras, C.D. Keroack, M.T. Duraisingh, K. Zarringhalam, M.-J. Gubbels. Single cell expression and chromatin accessibility of the Toxoplasma gondii lytic cycle identifies AP2XII-8 as an essential controller of a ribosome regulon. BioRXivs https://www.biorxiv.org/content/10.1101/2023.10.06.561197v1.
- Elsworth B., C. Keroack, Y. Rezvani, A. Paul, K. Barazorda, J. Tennessen, S. Sack, C. Moreira, M.J. Gubbels, M. Meyers, K. Zarringhalam, M. Duraisingh. 2023. Babesia divergens egress from host cells is orchestrated by essential and druggable kinases and proteases. Res Sq. rs.3.rs-2553721. doi: 10.21203/rs.3.rs-2553721/v1. PMCID: PMC10002801.
- Duraisingh M.T., M.J. Gubbels, K. Zarringhalam. 2023. A rising tide of parasite transcriptomics propels pathogen biology. PLoS Biol. 21(1):e3001997. doi: 10.1371/journal.pbio.3001997 . PMCID: PMC9876607
- Rezvani Y., C.D. Keroack, B. Elsworth, A. Arriojas, M.J. Gubbels, M.T. Duraisingh, K. Zarringhalam. 2022. Comparative single-cell transcriptional atlases of Babesia species reveal conserved and species-specific expression profiles. PLoS Biol. 20(9):e3001816. doi: 10.1371/journal.pbio.3001816 . PMCID: PMC9531838
- Nasuhidehnavi A., Y. Zhao, A. Punetha, A. Hemphill, H. Li, T.J. Bechtel, T. Rager, B. Xiong, V.I. Petrou, M.J. Gubbels, E. Weerapana, G.S. Yap. 2022. A Role for basigin in Toxoplasma gondii infection. Infect Immun. 90(8):e0020522. doi: 10.1128/iai.00205-22 . PMCID: PMC9387297
- Gubbels M.J., D.J.P. Ferguson, S. Saha, J.D. Romano, S. Chavan, V.A. Primo, C. Michaud, I. Coppens, K. Engelberg. 2022. Toxoplasma gondii's basal complex: the other apicomplexan business end Is multifunctional. Front Cell Infect Microbiol. 12:882166. doi: 10.3389/fcimb.2022.882166 . PMCID: PMC9103881
- Gubbels, M.-J., D.J.P. Ferguson, S. Saha, J. D. Romano, S. Chavan, V.A. Primo, C. Michaud, I. Coppens, K. Engelberg. 2022. Toxoplasma gondii’s basal complex: the other apicomplexan business end is multifunctional. Front Cell Infect Microbiol. 12:882166. doi: 10.3389/fcimb.2022.882166. PMCID: PMC9103881
- Engelberg, K., T.J. Bechtel, C. Michaud, E. Weerapana, and M.-J. Gubbels. 2022. Proteomic characterization of the Toxoplasma gondii cytokinesis machinery portrays an expanded hierarchy of its assembly and function. Nat Commun 13:4644. doi: 10.1038/s41467-022-32151-0 . PMCID: PMC9360017
- Primo Jr, V.A., Y. Rezvani, A. Farrell, C.Q. Murphy, J. Lou, A. Vajdi, G.T. Marth, K. Zarringhalam, and M.-J. Gubbels. 2021. The extracellular milieu of Toxoplasma’s lytic cycle drives lab-adaptation, primarily by transcriptional reprogramming. mSystems. Dec 21;6(6):e0119621. doi: 10.1128/mSystems.01196-21 . PMCID: PMC8651083
- Gubbels, M.-J., I. Coppens, K. Zarringhalam, M.T. Duraisingh, and K. Engelberg. The modular circuitry of apicomplexan cell division plasticity. Front Cell Infect Microbiol. (contribution to special issue “Celebrating Diversity: The Many Cell Cycles of Eukaryotic Microbes”) 11:670049. PMCID: PMC8072463
- Tagoe, D.N.A., A.A. Drozda, J. A. Falco, T. J. Bechtel, E. Weerapana, and M.-J. Gubbels. 2021. Ferlins and DOC2 in Toxoplasma microneme, rhoptry, and dense granule secretion. Life 11, 217. (contribution to special issue "Intracellular Trafficking and Organelle Biogenesis in Apicomplexan Parasites“) doi.org/10.3390/life11030217. PMCID: PMC7999867
- Tagoe, D.N.A., A. A. Drozda, I. Coppens, B.I. Coleman, and M-J. Gubbels. Toxoplasma ferlin1 is a versatile and dynamic mediator of microneme trafficking and secretion. bioRxiv.
- M.-J. Gubbels, C.D. Keroack, S. Dangoudoubiyam, H.L. Worliczek, A.S. Paul, C. Bauwens, B. Elsworth, K. Engelberg, D.K. Howe, I. Coppens, M.T. Duraisingh. 2020. Fussing about fission: defining variety among mainstream and exotic apicomplexan cell division modes. Front Cell Infect Microbiol. 10: 269. PMCID: PMC7289922
- Engelberg, K., C.-T. Chen, T.J. Bechtel, V. Sánchez Guzmán, A. Drozda, S. Chavan, E. Weerapana, and M.-J. Gubbels. 2020. The apical annuli of Toxoplasma gondii are composed of coiled-coil and signaling proteins embedded in the inner membrane complex sutures. Cell. Micro. 22:e13112 PMCID: PMC6925623
- Chen, C.-T. and M.-J. Gubbels. 2019. TgCep250 is dynamically processed through the division cycle and essential for structural integrity of the Toxoplasma centrosome. MBoC 30:1160-1169. PMID: 30865554
- Coleman, B.I. S. Saha, S. Sato, K. Engelberg, D.J.P. Ferguson, I. Coppens, M.B. Lodoen, and M.-J. Gubbels. 2018 A Member of the Ferlin Calcium Sensor Family Is Essential for Toxoplasma gondii Rhoptry Secretion, mBio 9: e01510-18. PMCID: PMC6168857
- Berry, L., C.-T. Chen, M.E. Francia, A. Guerin, A. Graindorge, J.-M. Saliou, M. Grandmougin, S. Wein, C. Bechara, J. Morlon-Guyot, Y. Bordat, M.-J. Gubbels, M. Lebrun, J.-F. Dubremetz and W. Daher. 2018 Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle, a prerequisite for productive endodyogeny. Cell Molec Life Sci. 75:4417-4443 PMCID: PMC6260807
- Saha, S., B.I. Coleman, R. Dubey, I.J. Blader, and M.-J. Gubbels corresponding author. 2017. Two phosphoglucomutase paralogs facilitate ionophore-triggered secretion of the Toxoplasma micronemes. mSphere. 2: e00521-17. PMCID: PMC5705807
- Dubey, R., B. Harrison, S. Dangoudoubiyam, G. Bandini, K. Cheng, A. Kosber, C. Agop-Nersesian, D.K. Howe, J. Samuelson, D.J.P. Ferguson, and M.-J. Gubbels. 2017. Differential roles for IMC proteins across Toxoplasma gondiiand Sarcocystis neurona development. mShere,.2: e00409-17 PMCID: PMC5296235
- Dubey, R., B.L. Staker, I.T. Foe, M. Bogyo, P.J. Myler, H.M. Ngô, and M.-J. Gubbels. 2017. Membrane skeletal association and post-translational allosteric regulation of Toxoplasma gondii GAPDH1. Mol. Microbiol. 103:618-634 PMCID: PMC5296235
- Weidner, J.M., S. Kanatani, H. Uchtenhangen, M. Varas-Godoy, T. Schulte, K. Engelberg, M.-J. Gubbels, H. Song Sun, R. Harrison, A. Achour, and A. Barragan. 2016. Toxoplasma gondii 14-3-3 protein is linked to a hypermigratory phenotype in parasitized immune cells. Cell Micro. 18:1537-1550 PMCID: PMC5040621
- Berry, L., C.-T. Chen, L. Reininger, T.G. Carvalho, H. El Hajj, J. Morlon-Guyot, Y. Bordat, M. Lebrun, M.-J. Gubbels, C. Doerig, and W. Daher. 2016. The conserved apicomplexan Aurora kinase 3 is involved in endodyogeny, duplication rate and parasite virulence. Cell Micro. 18:1106-1120. PMCID: PMC4961599
- Engelberg, K., F.D. Ivey, A. Lin, M. Kono, A. Lorestani, D. Faugno-Fusci, T.W. Gilberger, M. White, and M.-J. Gubbels. 2016. A MORN1-assocatiated HAD phosphatase in the basal complex is essential for Toxoplasma gondii daughter budding. Cell Micro. 18:1153-1171. PMCID: PMC4961593
- Skariah, S., O. Walwyn, K. Engelberg, M.-J. Gubbels, N. Kim, B. Lynch, C. Gaylets, A. Ali Sultan, and D. Mordue. 2016. The FIKK kinase of Toxoplasma gondii is not essential for the parasite’s lytic cycle. Int. J. Parasitol. 46:323-332. PMCID: PMC4844859
- Chen, C.-T., M. Farrell, J. de Leon, B. Nwagbara, P. Ebbert, D.J.P. Ferguson, L.A. Lowery, N. Morrissette, and M.-J. Gubbels. 2015. Compartmentalized Toxoplasma EB1 bundles spindle microtubules to secure accurate chromosome segregation. MBoC. 26:4562-4576. PMCID: PMC4678015
- Blader, I.J., B.I. Coleman, C.-T. Chen, and M.-J. Gubbels. 2015. The Toxoplasma gondii lytic cycle:15 years later. Ann Rev Microbiol 69: 463-485 (invited review). PMCID: PMC4659696
- Paul, A.S., S., Saha, K. Engelberg, R.Y. Jiang, B.I. Coleman, A.L. Kosber, C.-T. Chen, M. Ganter, N. Espy, T.-W. Gilberger, M.-J. Gubbels*, and M.T. Duraisingh*. 2015. Apicomplexan calcineurin regulates specific attachment of free parasites to host cells for infection. Cell Host Microbe. 18: 49-60. *co-corresponding author. PMCID: PMC4506782
- Chen, C.-T., and M.-J. Gubbels. 2015. Apicomplexan cell cycle flexibility: centrosome controls the clutch. Trends Parasitol. 31:229-230
- Brown, K.M. E. Suvorova, A. Farrell, A. McLain, A. Dittmar, G.B. Wiley, G.T. Marth, P.M. Gaffney, M.-J. Gubbels, M. White, and I. Blader. 2014. Forward genetic screening identifies a small molecule that blocks Toxoplasma growth by inhibiting both host- and parasite-encoded kinases. PLoS Path. 10(6):e1004180.
- Farrell, A., B.I. Coleman, B. Benenati, K.M. Brown, I. Blader, G.T. Marth, and M.-J. Gubbels. 2014. Whole genome profiling of spontaneous and chemical mutagenesis induced mutations in Toxoplasma gondii. BMC Genomics. 15: 354.
- Gubbels, M.-J., and Morrissette, N. 2013. The Cytoskeleton: structures and motility (chapter 13). In: Toxoplasma gondii: The Model Apicomplexan, 2nd edition. Eds.: L.M. Weiss and K. Kim. Elsevier Academic Press. ISBN: 9780123964816.
- Farrell, M., and M.-J. Gubbels. 2014. The Toxoplasma gondii kinetochore is required for centrosome association with the centrocone (spindle pole). Cell. Microbiol. 16: 78-94.
- Morlon-Guyot, J., L. Berry, C.-T. Chen, M.-J. Gubbels, M. Lebrun, and W. Daher. 2014. The Toxoplasma gondii Calcium Dependent Protein Kinase 7 is involved in early steps of parasite division and is crucial for parasite survival. Cell. Microbiol. 16: 95-114.
- Yang, N., A. Farrell, W. Niedelman, M. Melo, D. Lu, L. Julien, G.T. Marth, M.-J. Gubbels, J.P.J. Saeij. 2013 Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains. BMC Genomics. 14:467.
- Chen, C.-T. and M.-J. Gubbels. 2013. The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant. Journal of Cell Science. 126:3344-3355.
- Lorestani, A., F.D. Ivey, S. Thirugnanam, M.A. Busby, G.T. Marth, I. Cheeseman, and M.-J. Gubbels. 2012. Targeted proteomic dissection of Toxoplasma cytoskeleton sub-compartments using MORN1. Cytoskeleton. 69:1069-1085.
- Gubbels, M.-J. and M.T. Durasingh. 2012. Evolution of apicomplexan secretory organelles. Int. J. Parasitol. 42:1071-1081 (invited review). Highlighted as a Feature Article on the Malaria Nexus website.
- Bushkin, G.G., P. Magnelli, E. Motari, M.-J. Gubbels, J.P. Dubey, K. Miska, E. Bullitt, C.E. Costello, P.W. Robbins, and J. Samuelson. 2012. β-1,3-glucan, a druggable target, is part of a trabecular scaffold in inner layer of the oocyst wall of Toxoplasma and Eimeria. mBio. 3(5). pii: e00258-12.
- Anderson-White, B.R., J.R. Beck, C.-T. Chen, M. Meissner, P.J. Bradley, and M.-J. Gubbels. 2012. Cytoskeleton assembly in Toxoplasma gondii cell division. Int. Rev. Cell Mol. Biol. 298:1-31.
- Fung, C., J.R. Beck, S.D. Robertson, M.-J. Gubbels, and P.J. Bradley. Toxoplasma ISP4 is a central IMC sub-compartment protein whose localization depends on palmitoylation but not myristoylation. Mol. Biochem Parasitol. 184:99-108.
- Szatanek, T., B.R. Anderson-White, M. White, J. Saeij, and M.-J. Gubbels. 2012. Cactin is essential for G1 progression in Toxoplasma gondii. Mol. Micro. 84:566-577.
- Coleman, B.I., and M.-J. Gubbels. 2012. A genetic screen to isolate Toxoplasma gondii host cell egress mutants. J. Vis. Exp. 60:e3807.
- Farrell, A. S. Thirugnanam, A. Lorestani, J.D. Dvorin, K.P. Eidell, B.R. Anderson-White, D.J.P. Ferguson, M.T. Duraisingh, G.T. Marth, and M.-J. Gubbels. 2012. A DOC2 protein identified by mutational profiling is essential for apicomplexan parasite exocytosis. Science. 335:218-221.
- Jammallo*, L., K. Eidell*, P.H. Davis, F.J. Dufort, C. Cronin, S. Thirugnanam, T.C. Chiles, D.S. Roos, and M.-J. Gubbels. 2011. An insertional trap for conditional gene expression in Toxoplasma gondii: identification of TAF250 as an essential gene. Mol. Biochem. Parasitol. 175:133-143. (*equal contribution).
- Anderson-White, B.R., Ivey, F.D., Cheng, K. K., Szatanek, T., Lorestani, A., Beckers, C.J., Ferguson, D.J.P., Sahoo, N., and Gubbels, M.-J. 2010. A family of intermediate filament-like proteins is sequentially assembled into the cytoskeletal scaffold of Toxoplasma gondii. Cellular Microbiology 13:18-31.
- Lorestani, A., L. Sheiner, K. Yang, S.D. Robertson, N. Sahoo, C.F. Brooks, D.P.J. Ferguson, B. Striepen, and M.-J. Gubbels. 2010. A Toxoplasma MORN1 null mutant is defective in basal complex assembly and apicoplast division. PLoS ONE. 5:e12302.
- Eidell, K., Burke, T., and Gubbels, M.-J. 2010. Development of a screen to dissect Toxoplasma gondii egress. Molecular and Biochemical Parasitology 171(2): 97–10.
- Wilson, D.C., Grotenbreg, G.M., Liu, K.N., Zhao, Y., Frickel, E.-M., Gubbels, M.-J., Ploegh, H.L., and Yap, G.S. 2010. Differential regulation of effector- and central-memory responses to Toxoplasma gondii infection by IL-12 revealed by tracking of Tgd057-specific CD8+ T cells. PLoS Pathogens 6(3): e1000815.
- Bushkin, G.G., Ratner, D.M., Cui, J., Banerjee, S., Duraisingh, M.T., Jennings, C.V., Dvorin, J.D., Gubbels, M.-J., Robertson, S.D., Steffen, M., O’Keefe, B.R., Robbins, P.W., and Samuelson, J. 2010. Evidence for Darwinian selection against asparagine-linked glycans of Plasmodium and Toxoplasma. Eukaryotic Cell 9: 228–241.
- 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 198: 1625–1633.
- 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).
- 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).
- 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.
- 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.
- Gubbels, M.J., Mazumdar, J., van Dooren, G., and Striepen, B. 2006. Manipulating the Toxoplasma genome. In "The biology of Toxoplasma gondii." Soldati, D., and Ajioka, J. (Eds.). Horizon Scientific Pres, Norwich, UK.
- 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.