Physiological constraints on DNA replication and fidelity

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The blueprint of life is encoded in the DNA of an organism; this genetic program dictates what molecules will be produced in order to sustain growth and reproduction of the organism. The replication, repair, and (in some cases) damage of the bacterial genome is dependent upon the activity of specific proteins in the cell. What is remarkable is that the abundance of these proteins changes depending upon how rapidly the organism grows. Consequently, we expect a heretofore unexplored intrinsic and complex coupling between genome stability and cell growth. Our objective is to determine how the success of the growth program affects the fidelity of transmitting that program to subsequent generations. Over the past several decades, investigators have elucidated the molecular mechanisms underlying genetic maintenance and repair, although these mechanisms have been studied largely isolated from the physiological context of a growing organism. Our lab has recently formulated fundamental ‘growth laws’ that characterize constraints on resource allocation in growing bacteria. The resulting framework provides a means to interface molecular mechanisms with the growth-demands of the organism. Unraveling the interplay between growth physiology and genetic stability has important consequences for how we understand speciation and diversification, as well as informing clinical practice in the eradication of pathogenic infections.