Faculty & Research
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Molecular Biology Faculty

Zemer Gitai

associate Professor of Molecular Biology
director of graduate studies

 

Zemer Gitai

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Phone (609) 258-9420
locationLewis Thomas Lab, 353
Phone Lab (609) 258-9420
Faculty Assistant
Ellen Brindle-Clark
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Phone (609) 258-5419

 

Research Focus

Bacterial Cell Biology: Fundamentals of Cytoskeletal Dynamics, Polarity, and Mitosis

Life as we know it requires cellular asymmetry. Without asymmetry, our neurons would not process information, our intestines would not absorb nutrients, and pathogens would not be infectious. No cell is a homogeneous bag of enzymes; instead, cells have complex subcellular architectures with components that are localized to specific places at specific times. The specific architecture of each and every cell allows it to properly grow, divide, differentiate, and communicate. The mechanisms by which cells achieve their subcellular organization are thus fundamental to understanding how life works.

To study such a complicated process, we are initially focusing on a simple cell, the bacterium Caulobacter crescentus. Caulobacter has a unique life cycle during which it divides asymmetrically to produce daughters with different morphologies and fates. A rich variety of cell biological, genetic, biochemical, and genomic techniques make Caulobacter an ideal experimental system for our purposes.

The cytoskeleton plays an essential role in virtually every eukaryotic cellular process examined. Our exploration of Caulobacter cell biology has thus begun with the bacterial cytoskeleton. The absence of a cytoskeletal network was once believed to be a defining distinction between prokaryotes and eukaryotes. However, work in the past few years has shown that bacteria actually possess a full complement of cytoskeletal proteins including actin, tubulin, and intermediate filament protein homologs. The challenge remains to determine what these proteins do in the cell and how they do it.

We have initially focused on the actin homolog, MreB. During the Caulobacter cell cycle, MreB undergoes dynamic rearrangement involving a spiral that collapses into a ring, much like a slinky. Disrupting this dynamic structure dramatically perturbs cell morphogenesis, polarity, and chromosome segregation. Genetic analysis demonstrated that MreB instructs global cell polarity, while temporal studies with an MreB-inhibiting drug and MreB-ChIPs unearthed chromosomal loci that act as a centromere, directing segregation by associating with MreB. Together these results suggest that MreB plays a key role in integrating global positional information.

These findings have opened the door to several exciting avenues that we are currently pursuing. (1) Mechanistically, how does MreB direct polarity and mitosis? We are using genetic screens and biochemical assays to identify and functionally characterize MreB-interacting factors. (2) How is MreB dynamically rearranged? We are implementing new ultra-high-resolution protein labeling and imaging techniques to explore MreB’s dynamic structure. (3) Are there other key cellular regulators? We are performing a functional genomic screen to find all of the Caulobacter proteins with interesting subcellular localizations.

Our group will thus integrate cell biological, genetic, biochemical, biophysical, and genomic approaches to tackle fundamental questions in a simple model system. Eventually, I hope to investigate the similarities between prokaryotic and eukaryotic biology to provide insights into core conserved principles, and to exploit the differences for a new generation of antimicrobial targets.


Selected Publications

Persat A, Gitai Z. (2014) Bacterial evolution: rewiring modules to get in shape. Curr Biol. 24: R522-24. Pubmed

Persat A, Stone HA, Gitai Z. (2014) The curved shape of Caulobacter crescentus enhances surface colonization in flow. Nat Commun. 5:3824. Pubmed

Cowles KN, Moser TS, Siryaporn A, Nyakudarika N, Dixon W, Turner JJ, Gitai Z. (2013) The putative Poc complex controls two distinct Pseudomonas aeruginosa polar motility mechanisms. Mol Microbiol. 90: 923-38. Pubmed

Yakhnina AA, Gitai Z. (2013) Diverse functions for six glycosyltransferases in Caulobacter crescentus cell wall assembly. J Bacteriol. 195: 4527-35. Pubmed

Klein EA, Schlimpert S, Hughes V, Brun YV, Thanbichler M, Gitai Z. (2013) Physiological role of stalk lengthening in Caulobacter crescentus. Commun Integr Biol. 6: e24561. Pubmed

Wilson MZ, Gitai Z. (2013) Beyond the cytoskeleton: mesoscale assemblies and their function in spatial organization. Curr Opin Microbiol. 16: 177-83. Pubmed

Klein EA, Gitai Z. (2013) Draft genome sequence of uropathogenic Escherichia coli strain J96. Genome Announc. 1. pii: e00245-12. Pubmed

Bos J, Yakhnina AA, Gitai Z. (2012) BapE DNA endonuclease induces an apoptotic-like response to DNA damage in Caulobacter. Proc Natl Acad Sci. 109: 18096-101. Pubmed

Yakhnina AA, Gitai Z. (2012) The small protein MbiA interacts with MreB and modulates cell shape in Caulobacter crescentus. Mol Microbiol. 85: 1090-104. Pubmed

van Teeffelen S, Shaevitz JW, Gitai Z. (2012) Image analysis in fluorescence microscopy: bacterial dynamics as a case study. Bioessays. 34: 427-36. PubMed

Ingerson-Mahar M, Gitai Z. (2012) A growing family: the expanding universe of the bacterial cytoskeleton. FEMS Microbiol Rev. 36: 256-66. PubMed

Barry RM, Gitai Z. (2011) Self-assembling enzymes and the origins of the cytoskeleton. Curr Opin Microbiol. 14: 704-11. PubMed

Werner JN, Gitai Z. (2010) High-throughput screening of bacterial protein localization. Methods Enzymol. 471: 185-204. PubMed

Shebelut CW, Guberman JM, van Teeffelen S, Yakhnina AA, Gitai Z. (2010) Caulobacter chromosome segregation is an ordered multistep process. Proc Natl Acad Sci. 107: 14194-98. PubMed

Michaelis AM, Gitai Z. (2010) Dynamic polar sequestration of excess MurG may regulate enzymatic function. J Bacteriol. 192: 4597-605. PubMEd

Shaevitz JW, Gitai Z. (2010) The structure and function of bacterial actin homologs. Cold Spring Harb Perspect Biol. 2: a000364. PubMed

Ingerson-Mahar M, Briegel A, Werner JN, Jensen GJ, Gitai Z. (2010) The metabolic enzyme CTP synthase forms cytoskeletal filaments. Nat Cell Biol. 12: 739-46. PubMed

Cowles KN, Gitai Z. (2010) Surface association and the MreB cytoskeleton regulate pilus production, localization and function in Pseudomonas aeruginosa. Mol Microbiol. 76: 1411-26. PubMed

Werner JN, Chen EY, Guberman JM, Zippilli AR, Irgon JJ, Gitai Z. (2009) Quantitative genome-scale analysis of protein localization in an asymmetric bacterium. Proc Natl Acad Sci. 106: 7858-63. PubMed

Gitai Z. (2009) New fluorescence microscopy methods for microbiology: sharper, faster, and quantitative. Curr Opin Microbiol. 12: 341-46. PubMed

Huang KC, Mukhopadhyay R, Wen B, Gitai Z, Wingreen NS. (2008) Cell shape and cell-wall organization in Gram-negative bacteria. Proc Natl Acad Sci. 105: 19282-87. PubMed

Guberman JM, Fay A, Dworkin J, Wingreen NS, Gitai Z. (2008) PSICIC: noise and asymmetry in bacterial division revealed by computational image analysis at sub-pixel resolution. PLoS Comput Biol. 4: e1000233. PubMed

Shebelut CW, Jensen RB, Gitai Z. (2008) Growth conditions regulate the requirements for Caulobacter chromosome segregation. J Bacteriol. 191: 1097-100 PubMed

Silhavy TJ, Gitai Z. (2008) Sex to the rescue. Nat Methods. 5: 759-60. PubMed

Gitai Z. (2007) Diversification and specialization of the bacterial cytoskeleton. Curr Opin Cell Biol. 19: 5-12. PubMed

Gitai Z. (2006) Plasmid segregation: a new class of cytoskeletal proteins emerges. Curr Biol. 16: R133-36. Pubmed

Gitai Z, Thanbichler M, Shapiro L. (2005) The choreographed dynamics of bacterial chromosomes. Trends Microbiol. 13: 221-28. PubMed

Gitai Z, Dye NA, Reisenauer A, Wachi M, Shapiro L. (2005) MreB actin-mediated segregation of a specific region of a bacterial chromosome. Cell. 120: 329-41. PubMed

Gitai Z. (2005) The new bacterial cell biology: moving parts and subcellular architecture. Cell. 120: 577-86. PubMed

Dye NA, Pincus Z, Theriot JA, Shapiro L, Gitai Z. (2005) Two independent spiral structures control cell shape in Caulobacter. Proc Natl Acad Sci. 102: 18608-13. PubMed

Gitai Z, Dye N, Shapiro L. (2004) An actin-like gene can determine cell polarity in bacteria. Proc Natl Acad Sci. 101: 8643-48. PubMed

Gitai Z, Shapiro L. (2003) Bacterial cell division spirals into control. Proc Natl Acad Sci. 100: 7423-24. PubMed

 

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