Biology Department Faculty

Marc-Jan Gubbels

Professor

Department

Biology

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鈥檚 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鈥檚 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

  • Engelberg, K. C. Bauwens, D.J.P. Ferguson and听M.-J. Gubbels.听2024. Co-dependent formation of the听Toxoplasma gondii听subpellicular microtubules and inner membrane skeleton. bioRxiv 2024.05.25.595886; doi:听
  • Tagoe*, D.N.A., A. Ribeiro E Silva*, A.A. Drozda, I. Coppens, B.I. Coleman and听M-J. Gubbels.听2024.Toxoplasma听ferlin1 is a versatile and dynamic mediator of microneme trafficking and secretion. BioRXivs:听.听Scientific Reports听鈥 in press. *equal author contribution
  • Lou*, J. Y. Rezvani*, A. Argenis, D. Degras, Y. Wu, N. Shankar, C.D. Keroack,M.T. Duraisingh, K. Zarringhalam,听M.-J. Gubbels.听Single cell expression and chromatin accessibility of the听Toxoplasma gondii听lytic cycle identifies AP2XII-8 as an essential controller of a ribosome regulon.听Nature Communications, 24:7419.听. PMCID:听听*equal author contribution
  • Elsworth B., C. Keroack, Y. Rezvani, A. Paul, K. Barazorda, J. Tennessen, S. Sack, C. Moreira,听M.J. Gubbels, M. Meyers, K. Zarringhalam, M. Duraisingh. 2023.听Babesia divergens听egress from host cells is orchestrated by essential and druggable kinases and proteases.听Res Sq.听rs.3.rs-2553721. doi:听听PMCID:听.
  • Duraisingh M.T.,听M.J.Gubbels, K. Zarringhalam. 2023. A rising tide of parasite transcriptomics propels pathogen biology.听PLoS Biol.听21(1):e3001997. doi:听.听PMCID:听
  • 听Rezvani Y., C.D. Keroack, B. Elsworth, A. Arriojas,听M.J.Gubbels, M.T. Duraisingh, K. Zarringhalam. 2022. Comparative single-cell transcriptional atlases of听Babesia听species reveal conserved and species-specific expression profiles.听PLoS Biol.听20(9):e3001816. doi:听.听PMCID:听
  • Nasuhidehnavi A., Y. Zhao, A. Punetha, A. Hemphill, H. Li, T.J. Bechtel, T. Rager, B. Xiong, V.I. Petrou,听M.J.Gubbels, E. Weerapana, G.S. Yap. 2022. A Role for basigin in听Toxoplasma gondii听infection.听Infect Immun.听90(8):e0020522. doi:听.听PMCID:听
  • Gubbels M.J., D.J.P. Ferguson, S. Saha, J.D. Romano, S. Chavan, V.A. Primo, C. Michaud, I. Coppens, K. Engelberg. 2022.听Toxoplasma gondii's basal complex: the other apicomplexan business end Is multifunctional.听Front Cell Infect Microbiol.听12:882166. doi:听.听PMCID:听
  • Gubbels, M.-J.,听D.J.P. Ferguson, S. Saha, J. D. Romano, S. Chavan, V.A. Primo, C. Michaud, I. Coppens, K. Engelberg. 2022.Toxoplasma gondii鈥檚 basal complex: the other apicomplexan business end is multifunctional.听Front Cell Infect Microbiol. 12:882166. doi: 10.3389/fcimb.2022.882166.听PMCID:听
  • Engelberg, K.,听T.J. Bechtel,听C. Michaud,听E. Weerapana,听and听M.-J. Gubbels.听2022.听Proteomic characterization of the听Toxoplasma gondii听cytokinesis machinery portrays an expanded hierarchy of its assembly and function.听Nat Commun听13:4644.听doi:听.听听PMCID:听
  • Primo Jr, V.A.,听Y. Rezvani, A. Farrell,听C.Q. Murphy, J. Lou,听A. Vajdi, G.T. Marth, K. Zarringhalam, and听M.-J. Gubbels.听2021. The extracellular milieu of听Toxoplasma鈥檚 lytic cycle drives lab-adaptation, primarily by transcriptional reprogramming. mSystems. Dec 21;6(6):e0119621. doi:听.听PMCID:听
  • Gubbels,M.-J.,听I. Coppens, K. Zarringhalam, M.T. Duraisingh, and听K.听Engelberg.听The modular circuitry of apicomplexan cell division plasticity.听Front Cell Infect Microbiol. (contribution to special issue听鈥淐elebrating Diversity: The Many Cell Cycles of Eukaryotic Microbes鈥)听11:670049.听PMCID:听
  • Tagoe, D.N.A., A.A.Drozda,听J. A. Falco, T. J. Bechtel, E. Weerapana, and听M.-J. Gubbels. 2021.听Ferlins and DOC2 in听Toxoplasma听microneme, rhoptry, and dense granule secretion.听Life听11, 217. (contribution to special issue听"Intracellular Trafficking and Organelle Biogenesis in Apicomplexan Parasites鈥)听. PMCID:听
  • Tagoe, D.N.A., A. A. Drozda,听I. Coppens, B.I. Coleman, and M-J. Gubbels. bioRxiv.
  • M.-J. Gubbels,听C.D. Keroack, S.听Dangoudoubiyam,听H.L. Worliczek, A.S. Paul, C. Bauwens, B. Elsworth, K. Engelberg, D.K. Howe, I. Coppens, M.T. Duraisingh. 2020. 听Front Cell Infect Microbiol. 10: 269.听PMCID:听PMC7289922听
  • Engelberg, K., C.-T. Chen, T.J. Bechtel, V. S谩nchez Guzm谩n, A. Drozda, S. Chavan, E. Weerapana, and M.-J. Gubbels. 2020. . Cell. Micro.听22:e13112 PMCID: PMC6925623
  • Chen, C.-T. and M.-J. Gubbels. 2019. . MBoC 30:1160-1169. PMID: 30865554
  • Coleman,听B.I. S. Saha,听S. Sato,听K. Engelberg,听D.J.P. Ferguson,听I. Coppens,听M.B. Lodoen,听and M.-J. Gubbels. 2018 听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 . 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.
  • 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.
  • Dubey, R.,听B.L. Staker, I.T. Foe, M. Bogyo, P.J. Myler, H.M. Ng么, andM.-J. Gubbels. 2017. .听Mol. Microbiol.听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.听.听Cell Micro.听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.听.听Cell Micro.听18:1106-1120.听PMCID: PMC4961599
  • Engelberg, K., F.D. Ivey, A. Lin,听M. Kono, A. Lorestani, D. Faugno-Fusci, T.W. Gilberger, M. White, and M.-J. Gubbels. 2016. .听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.听.听Int. J. Parasitol.听46:323-332. PMCID: PMC4844859
  • Chen, C.-T., M. Farrell,听J. de Leon, B. Nwagbara, P. Ebbert, D.J.P. Ferguson, L.A. Lowery, N. Morrissette, and M.-J.听Gubbels. 2015.听.听MBoC.听26:4562-4576. PMCID: PMC4678015
  • Blader, I.J.,听B.I. Coleman, C.-T. Chen, and M.-J.听Gubbels. 2015. .听Ann Rev Microbiol听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. .听Cell Host Microbe.听18:听49-60. *co-corresponding author.听PMCID:听PMC4506782
  • Chen, C.-T., and M.-J. Gubbels. 2015. . Trends Parasitol.听31:229-230
  • Brown, K.M. E. Suvorova, A. Farrell, A. McLain, A. Dittmar, G.B. Wiley, G.T. Marth, P.M. Gaffney,听M.-J. Gubbels,听M. White, and I. Blader. 2014.听. PLoS Path.听10(6):e1004180.
  • Farrell, A., B.I. Coleman, B. Benenati, K.M. Brown, I. Blader, G.T. Marth, and M.-J. Gubbels. 2014. . BMC Genomics. 15: 354.
  • Gubbels, M.-J., and Morrissette, N. 2013. The Cytoskeleton: structures and motility (chapter 13). , 2nd edition. Eds.: L.M. Weiss and K. Kim. Elsevier Academic Press. ISBN: 9780123964816.
  • Farrell, M., and M.-J. Gubbels. 2014. . Cell. Microbiol. 16: 78-94.
  • Morlon-Guyot, J., L. Berry, C.-T. Chen, M.-J. Gubbels, M. Lebrun, and W. Daher. 2014. . Cell. Microbiol.听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. . BMC Genomics. 14:467.
  • Chen, C.-T. and M.-J. Gubbels. 2013. . 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. . Cytoskeleton. 69:1069-1085.
  • Gubbels, M.-J. and M.T. Durasingh. 2012. . 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. . 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. . Int. Rev. Cell Mol. Biol. 298:1-31.听
  • Fung, C., J.R.听 Beck, S.D. Robertson, M.-J. Gubbels, and P.J. Bradley. . Mol. Biochem Parasitol.听184:99-108.
  • Szatanek, T., B.R. Anderson-White, M. White, J. Saeij, and M.-J. Gubbels. 2012. . Mol. Micro. 84:566-577.
  • Coleman, B.I., and M.-J. Gubbels. 2012. . 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. . 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. . Mol. Biochem. Parasitol.听175:133-143. (*equal contribution).
  • Anderson-White, B.R., Ivey, F.D., Cheng, K. K., Szatanek, T., Lorestani, A.,听听 Beckers, C.J., Ferguson, D.J.P., Sahoo, N., and Gubbels, M.-J. 2010. . Cellular Microbiology听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. . PLoS ONE. 5:e12302.
  • Eidell, K., Burke, T., and Gubbels, M.-J. 2010. . Molecular and Biochemical Parasitology 171(2): 97鈥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. . PLoS Pathogens 6(3): e1000815.
  • Bushkin, G.G., Ratner, D.M.,听Cui, J., Banerjee, S., Duraisingh, M.T., Jennings, C.V., Dvorin, J.D., Gubbels, M.-J., Robertson, S.D., Steffen, M., O鈥橩eefe, B.R., Robbins, P.W., and Samuelson, J. 2010. . Eukaryotic Cell 9: 228鈥241.
  • Frickel, E.M., Sahoo, N., Hopp, J., Gubbels, M.-J., Craver, M.P., Knoll, L.J., Ploegh, H., and Grotebreg, G. 2008. . The Journal of Infectious Diseases 198: 1625鈥1633.
  • Gubbels, M.-J., White, M., and Szatanek, T. 2008. ? International Journal for Parasitology 38: 1343鈥1358 (Invited Review).
  • Muskavitch, M., Barteneva, N., and Gubbels, M.-J. 2008. . Combinatorial Chemistry & High Throughput Screening 11: 629鈥649 (Invited Review).
  • Ferguson, D.J.P., Sahoo, N., Pinches, R.A., Bumstead, J.M., Tomley, F.M., and Gubbels, M.-J. 2008. . Eukaryotic Cell 7: 698鈥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. . PLoS Pathogens 4(2): e36 (0001鈥0015) (Editor鈥檚 Pick).
  • Frickel, E.-M., Quesada, V., Muething, L., Gubbels, M.-J., Spooner, E., Ploegh, H., and Artavanis-Tsakonas, K. 2007. . Cellular Microbiology 6: 1601鈥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. . Journal of Cell Science 119: 2236鈥2245.