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Bacterial Growth Physiology


An important goal of modern biology is to connect molecular control strategies with the physiology of the organism. Recently, the strong indirect control bacterial growth itself imposes on the level of gene expression has become more widely appreciated. This interdependence between cell growth and gene expression has been observed for a long time, but it is only in the last few years that the origins and consequences of these so-called growth laws have been explored in detail.

In 1958, Schaechter, Maaloe and Kjeldgaard observed that certain macroscopic features of bacterial composition, for example the RNA/Protein ratio, are functions of growth rate alone. That is, irrespective of whatever microscopic adaptation and regulation is going on, some global strategy synchronizes the parts to control cell growth and composition. Using experimental and theoretical methods, we are uncovering what underlies this global control, and gives rise to the robust e,mpirical relationships we call the growth laws. Furthermore, by perturbing the growth program through various means, new growth laws emerge that point to a deep coupling between core catabolism and growth rate control.

My present research focus is to examine the consequences of these growth laws, specifically as a mechanism for generating distinct sub-populations in a culture that shares identical DNA (phenotypic bistability). This multidisciplinary research program brings together modern methods in proteomics, single-molecule microscopy, microbiology and biochemistry, integrated together using the tools and techniques of mathematical physics.

This work is being done in collaboration with Terry Hwa at the University of California, San Diego, and was recently published in Science.

Background reading:

The original article by Schaechter, Maaloe and Kjeldgaard, Journal of General Microbiology 19: 592-606 (1958).
A personal history by Cooper, Journal of General Microbiology 139: 1117-1124 (1993).
A general commentary by Neidhardt, Journal of Bacteriology 181: 7405-7408 (1999).

More recent work:

A meticulous study of the growth-rate dependence of a variety of cellular processes, and their consequences, are described in this article by Klumpp, Zhang and Hwa, Cell 139: 1366-1375 (2009).
A general review, focused on applications in synthetic biology and biotechnology by Scott and Hwa, Current Opinion in Biotechnology DOI:10.1016/j.copbio.2011.04.014 (2011).
©2008 Matt Scott. Layout design created by Francis Poulin.