Understanding how cells grow and divide has profound impacts on basic science, biotechnology, and medicine. Despite recent advances in molecular biology and biochemistry, a central challenge remains: bridging the nanometer-scale activities of proteins and the construction of entire cells. Although the mechanisms of bacterial proliferation have been a major focus of research for over a century, it has remained difficult to determine how cellular structure and organization are dynamically controlled due to the central—yet neglected—importance of physical factors.
To address these knowledge gaps, our lab pursues research directions that span from the atomic to the multicellular scales. We investigate the physical nature of intracellular spatial organization, mechanics, and kinetics by leveraging top-down approaches based on cellular-scale observations, bottom-up approaches based on biophysical molecular observations, and computational modeling that connects the two paradigms. Understanding cellular growth and form remains a fascinating, multifaceted challenge with obvious implications for health and disease. In addition to the importance of bacteria as a model system for basic science, uncovering the general physical rules that underlie how bacteria grow and divide will have important applications for controlling bacterial communities and developing novel strategies in synthetic biology.
|Mapping the spatial pattern of bacterial growth|
During growth, the molecular machinery must interact with the cell’s geometry; for example, the bacterial actin homolog MreB coordinates localization of the cell-wall synthesis machinery. We recently demonstrated that MreB preferentially localizes to regions of negative curvature, directing growth away from the poles and actively straightening locally curved regions of the cell (Ursell et al., 2014) in order to maintain robust, uniform growth at the cellular scale. Through transient inhibition of cell-wall synthesis, we found that spherical E. coli cells robustly revert to a rod shape within several generations after inhibition cessation through targeted cell-wall synthesis regulated by MreB (Billings et al., 2014). Our results thus indicate that MreB provides the geometric measure that allows E. coli to both establish and regulate its morphology.
Principles of bacterial cell-size determination revealed by cell-wall synthesis perturbations.
Tropini C, Lee TK, Hsin J, Desmarais SM, Ursell T, Monds RD†, Huang KC†.
Cell Rep. 2014 Nov 20;9(4):1520-7. doi: 10.1016/j.celrep.2014.10.027. Epub 2014 Nov 6.
De novo morphogenesis in L-forms via geometric control of cell growth.
Billings G, Ouzounov N, Ursell T, Desmarais SM, Shaevitz J, Gitai Z†, Huang KC†.
Mol Microbiol. 2014 Sep;93(5):883-96. doi: 10.1111/mmi.12703. Epub 2014 Jul 23.
How and why cells grow as rods.
Chang F†, Huang KC†.
BMC Biol. 2014 Aug 2;12:54. doi: 10.1186/s12915-014-0054-8. Review.
Rod-like bacterial shape is maintained by feedback between cell curvature and cytoskeletal localization.
Ursell TS, Nguyen J, Monds RD, Colavin A, Billings G, Ouzounov N, Gitai Z, Shaevitz JW, Huang KC.
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):E1025-34. doi: 10.1073/pnas.1317174111. Epub 2014 Feb 18.
Analysis of surface protein expression reveals the growth pattern of the gram-negative outer membrane.
Ursell TS*, Trepagnier EH*, Huang KC†, Theriot JA†.
PLoS Comput Biol. 2012;8(9):e1002680. doi: 10.1371/journal.pcbi.1002680. Epub 2012 Sep 27.
*Co-first authors †Co-corresponding authors