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Bacterial cell biology: growth, division, and shape regulation
The bacterial cell, once viewed as lacking internal organization, is in fact exquisitely structured at the subcellular level, and this spatial organization is critical for cellular survival and reproduction. As in eukaryotes, prokaryotic cell shape and internal structure are defined and dynamically remodeled by cytoskeletal elements. These proteins play critical roles in essential processes like cytokinesis and chromosome segregation, making them attractive targets for the development of novel antibiotics. Nevertheless, our understanding of the physiological functions of bacterial cytoskeletal proteins and the mechanisms by which they carry out their roles is still in its infancy. Our lab focuses on investigating cell biological processes in bacteria, with current effort concentrated on understanding cytokinesis in the model bacterium, Caulobacter crescentus. The mechanisms underlying cell cycle progression and development are well-characterized in Caulobacter, making it an ideal system to address cytoskeletal function and shape regulation in the context of a well-defined cell cycle regulatory paradigm.
To tackle the question of how bacterial cells divide, we focus in large part on the function and regulation of the highly conserved tubulin-like protein, FtsZ. FtsZ is thought to act as a scaffold for assembly of the cytokinetic machinery, to generate constrictive forces that drive division, and, ultimately, to direct remodeling of the cell wall. However, the molecular details of FtsZ function are largely unknown. To gain insight into the mechanisms and regulation of bacterial growth and division, we are asking questions such as: • How do the superstructure and dynamics of FtsZ polymers relate to its function? • How is FtsZ attached to the membrane, and (how) does it generate force? • How does FtsZ direct remodeling of the cell wall? • How is cell division coordinated with other morphogenetic events? • How do bacteria adapt their growth to changing environmental conditions?
We take a multi-faceted approach to address these questions, combining bacterial genetics, microscopy, biochemistry, and in vitro reconstitution to obtain a comprehensive view of the mechanisms of cell division and shape regulation.
These studies will inform models for how proteins at the division site direct cell growth and division and how these processes are integrated with other cell cycle events in time and space. In light of the high degree of conservation of cell division proteins among bacteria, our results will be relevant to the vast majority of bacterial species, including important human and animal pathogens.
Meier EL, Qing Y, Daitch AK, Jensen GJ, Goley ED (2017) FtsEX-mediated regulation of inner membrane fusion and cell separation reveals morphogenetic plasticity in Caulobacter crescentus. bioRxiv. doi: http://dx.doi.org/10.1101/124214. [pre-print]
Woldemeskel SA and Goley ED (2017) Shapeshifting to survive: shape determination and regulation in Caulobacter crescentus. Trends Microbiol. In press. [Review]
Xiao J and Goley ED. (2016) Redefining the roles of the FtsZ-ring in bacterial cytokinesis. Curr Opin Microbiol. 34:90-96 [Review]
Meier EL, Razavi S, Inoue T, Goley ED. (2016) A novel membrane anchor for FtsZ in linked to cell wall hydrolysis in Caulobacter crescentus. Mol Microbiol. 101: 265-280.
Sundararajan K, Miguel A, Desmarais SM, Meier EL, Huang KC, and Goley ED. (2015) The bacterial tubulin FtsZ requires its intrinsically disordered linker to direct robust cell wall construction. Nat Commun. 6:7281.
Meier EL and Goley ED. (2014) Form and function of the bacterial cytokinetic ring. Curr Opin Cell Biol. 26:19-27
Goley ED (2013) Tiny cells meet big questions: a closer look at bacterial cell biology. Mol Biol Cell. 24:1099-102.
Biteen JS, Goley ED, Shapiro L, Moerner WE. (2012) Three-Dimensional Super-Resolution Imaging of the Midplane Protein FtsZ in Live Caulobacter crescents cells Using Astigmatism. Chemphyschem. 13:1007-12.bsp;
Goley ED*, Yeh YC*, Hong SH, Fero MJ, Abeliuk E, McAdams HH, Shapiro L. (2011) Assembly of the Caulobacter cell division machine. Mol. Micro. 80:1680-1698.
Hsiao-lu DL, Lord SJ, Iwanaga S, Zhan K, Xie H, Williams JC, Wang H, Bowman GR, Goley ED, Shapiro L, Tweig RJ, Rao J, Moerner WE. (2010) Superresolution Imaging of Targeted Proteins in Living Cells Using Photoactivatable Organic Fluorophores. J Am Chem Soc. 132:15099-15101.
Goley ED, Dye NA, Werner JN, Gitai Z, Shapiro L. (2010) Imaging-based identification of a critical regulator of FtsZ protofilament curvature in Caulobacter. Mol. Cell. 39:975-987.
Goley ED, Comolli LR, Fero KE, Downing KH, Shapiro L. (2010) DipM links peptidoglycan remodeling to outer membrane organization in Caulobacter. Mol. Micro. 77:56-73.
Goley ED, Toro E, McAdams HH, Shapiro L. (2009) Dynamic Chromosome Organization and Protein Localization Coordinate the Regulatory Circuitry that Drives the Bacterial Cell Cycle. Col Spring Harb. Symp. Quant. Biol. 74:55-64. [Review]
Goley ED, Iniesta AA, Shapiro L. (2007) Cell cycle regulation in Caulobacter: location, location, location. J. Cell Sci. 120: 3501-7. [Review]