Spatiotemporal cell-shape regulation by the bacterial cytoskeleton
Abstract/Contents
- Abstract
- The study of microbe morphology uniquely offers a collision of the simple and hyper complex, both in the model organisms like E. coli, and the tools used to dissect them. At first glance, a microbe needs to do nothing more than incorporate nutrients and replicate itself. Yet observations dating back nearly six decades demonstrate that bacteria exhibit precise regulation of growth and form robust across multi-fold changes in mass. From these simple observations, the model that a bacterium is nothing more than a bag of enzymes becomes insufficient to explain the rich and robust landscape of morphology they can achieve. In this work, we seek to expand and expound the molecular mechanisms by which bacteria regulate their shape, using a set of diverse experimental and computational techniques. In the first chapter, we offer a colloquial introduction to bacterial morphology and the major molecular components known to be involved. The following three chapters include their own, more technical introductions. In the second chapter, we present a molecular model of MreB, the bacterial cytoskeletal protein thought to be responsible for spatially organizing the growth of the cell shape-determining cell wall. This model, based on analysis of molecular dynamic simulations, was published in 2014 and subsequently confirmed by an independent lab via crystallography. Our molecular models provide a reference point from which to interpret a growing diversity of disparate experimental results. In the third chapter, we explore how direct molecular interaction between MreB and other cell wall synthesis proteins -- namely RodZ -- can drive changes in the biophysical properties of the bacterial cytoskeleton. This chapter relies on simple but crucial set of observational experiments to reveal that the properties of the bacterial cytoskeleton vary widely in the course of normal bacterial growth. We identify potential protein interactions that appear to directly bind to and alter the biophysical properties of the MreB cytoskeleton. This work is currently in review at Nature Microbiology. In the final chapter, we expand the scope of focus to broadly identify possible interactions between all essential genes in the model bacteria Bacillus subtilis using a variety of experimental, genetic and bioinformatics techniques. In particular, we offer a novel insight into how the depletion of nearly 300 unique proteins drives a diverse set of changes in microbial morphology, highlighting a large number of molecular players previously not associated with changes in growth. Taken together, these chapters represent three unique scopes -- molecular, subcellular and cellular, that work in concert to answer questions about bacterial morphology and its regulation. The results presented herein, and the novel experimental assays developed in the process, present tangible advances in our understanding of bacterial morphology, and expands the list of known unknowns left to pursue.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Colavin, Alexandre Galinato |
|---|---|
| Associated with | Stanford University, Biophysics Program. |
| Primary advisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Jarosz, Daniel |
| Thesis advisor | Pande, Vijay |
| Advisor | Jarosz, Daniel |
| Advisor | Pande, Vijay |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Alexandre Galinato Colavin. |
|---|---|
| Note | Submitted to the Program in Biophysics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Alexandre Colavin
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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