Cell growth, gene expression, and their interdependence
DOI: 10.1063/1.3541936
Cell growth, gene expression, and their interdependence. If given ample food, bacteria proliferate exponentially. If given little or low-quality food, bacteria proliferate sluggishly. Behind that adjustable growth lies a complex web of interconnected molecular pathways, the elucidation of which is a major goal in biology. But, as Terence Hwa of the University of California, San Diego, and his collaborators demonstrate, you can accurately model the outcome of those complex reactions without knowing the details. Hwa and his colleagues based their model on experiments that revealed the relationships between proliferation rate, nutrient quality, and the ratio of RNA to protein inside the bacteria. That ratio, which is straightforward to measure, is significant because all proteins are made by RNA-rich ribosomes: The more ribosomes in a cell, the faster the cell can grow and multiply. The mathematical relations that emerged from the UCSD team’s analysis are simple and linear, and they reflect how cells allocate resources. In a nutrient-rich environment, the cell can afford to synthesize ribosomes at the expense of metabolic proteins, but when nutrients are scarce, metabolic proteins are synthesized at the expense of ribosomes. The balance between the two classes of biomolecule determines the growth rate. To test their model over a broad range of parameter space, Hwa and his colleagues observed two kinds of mutant: one whose ribosomes translate more slowly and one that overproduces a useless protein. The model passed. Hwa likens it to Ohm’s law, which enables electrical engineers to design circuits without knowing the band theory of electrical conduction. Given that mutant bacteria are used to make drugs and other useful chemicals, the UCSD model could prove similarly useful. (
