The Glotzer lab focuses on questions related to cell organization. How do cells coordinate the position of the contractile ring with the position of the spindle? By what mechanisms are cortical domains that mediate cell polarization assembled and maintained? How do cells regulate cortical contractility during developmental morphogenesis?
To answer these questions, we use the nematode C. elegans, cultured human cells, budding yeast, and Drosophila as model systems and we combine forward and reverse genetics, biochemistry, and live cell imaging. Through these approaches we have discovered and extensively characterized the centralspindlin complex, a multifunctional protein complex that regulates essentially every step of cytokinesis.
Not only are centralspindlin and Ect2 implicated in cell division, they are also implicated in the evolution of animals. Phylogenomic and structural analysis indicates that the last common ancestor of animals had the centralspindlin complex and Ect2 and the motifs that mediate inter-subunit interactions - they appear evolutionarily fixed. Some species of Choanoflagellate - the closest taxonomic neighbors of animals - have proteins related to centralspindlin and Ect2 but the interfaces that mediate their interactions are not well conserved. Metazoan germlines are organized in cysts, that form via incomplete cytokinesis. We propose that the evolutionary refinement of centralspindlin enabled the formation of such cysts and the ability of spindle positioning to direct cell division.
We have pioneered the use of optogenetics to dissect spatiotemporally regulated processes. Using these approaches, we have demonstrated that RhoA activation is sufficient to induce cleavage furrows irrespective of the position of the spindle or the stage of the cell cycle. Likewise, we obtained direct evidence that positive feedback is active during yeast cell polarization. By combining optogenetics with "conventional" genetics and live cell imaging we can directly test models for how cells endow well defined cortical regions with distinct properties that are required for complex cellular events, like cell division, cell polarization, and tissue scale morphogenetic events, such as gastrulation.
European Molecular Biology Labs
Heidelberg, Germany
Postdoc
1997
University of California, San Francisco
San Francisco, CA
Ph.D - Cell Biology
1993
University of California, Berkeley
Berkeley, CA
A.B. - Mathematics
1985
A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa.
A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa. Curr Biol. 2025 Jul 07; 35(13):3251-3262.e1.
PMID: 40532703
A minimal mathematical model for polarity establishment and centralspindlin-independent cytokinesis.
A minimal mathematical model for polarity establishment and centralspindlin-independent cytokinesis. J Cell Sci. 2025 Jun 01; 138(11).
PMID: 40341916
Projective light-sheet microscopy with flexible parameter selection.
Projective light-sheet microscopy with flexible parameter selection. Nat Commun. 2024 Mar 29; 15(1):2755.
PMID: 38553438
Apical polarity and actomyosin dynamics control Kibra subcellular localization and function in Drosophila Hippo signaling.
Apical polarity and actomyosin dynamics control Kibra subcellular localization and function in Drosophila Hippo signaling. Dev Cell. 2023 10 09; 58(19):1864-1879.e4.
PMID: 37729921
Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation.
Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation. Elife. 2022 12 19; 11.
PMID: 36533896
Small GTPases modulate intrinsic and extrinsic forces that control epithelial folding in Drosophila embryos.
Small GTPases modulate intrinsic and extrinsic forces that control epithelial folding in Drosophila embryos. Small GTPases. 2021 Sep-Nov; 12(5-6):416-428.
PMID: 33985411
Cortical recruitment of centralspindlin and RhoA effectors during meiosis I of Caenorhabditiselegans primary spermatocytes.
Cortical recruitment of centralspindlin and RhoA effectors during meiosis I of Caenorhabditiselegans primary spermatocytes. J Cell Sci. 2021 02 08; 134(3).
PMID: 33468621
Rho1 activation recapitulates early gastrulation events in the ventral, but not dorsal, epithelium of Drosophila embryos.
Rho1 activation recapitulates early gastrulation events in the ventral, but not dorsal, epithelium of Drosophila embryos. Elife. 2020 11 17; 9.
PMID: 33200987
Competition between kinesin-1 and myosin-V defines Drosophila posterior determination.
Competition between kinesin-1 and myosin-V defines Drosophila posterior determination. Elife. 2020 02 14; 9.
PMID: 32057294
PLK1 plays dual roles in centralspindlin regulation during cytokinesis.
PLK1 plays dual roles in centralspindlin regulation during cytokinesis. J Cell Biol. 2019 04 01; 218(4):1250-1264.
PMID: 30728176
Keith Porter Fellow
Keith Porter Endowment
2004
EMBO Member
2003