Almost all organisms must respond to challenges imposed by a dynamic external environment. Macro-organisms can choose to move to a better location. The small size of bacteria dictates a different strategy: they must stay and fight, responding by regulating physiological changes as best they can. Regulatory networks consisting of interconnected environment sensing and response components underlie this ability.
The goal of the research project is to determine the genetic and physiological basis, and ecological and evolutionary consequences, of changes in a regulatory network controlling utilization of a common sugar, lactose. To do this, the investigators will develop theoretical models that account for the structure of the network, and can predict how changes will affect bacterial growth in different environments. The investigators will test these predictions using populations of the bacterium Escherichia coli that have been experimentally evolved in defined environments with different lactose availability. Preliminary results indicate that these populations have changed the way in which they regulate their lactose utilization network in a way that depends on their selective environment. By combining theoretical and experimental approaches, how and why regulatory changes have evolved will be addressed.
Understanding how bacteria adapt to new environments is essential to many disciplines: medicine, public health, industry, and as a foundation of biology. Changes in gene regulation account for much of the immediate adaptation of organisms to new environmental challenges, yet the ability to manipulate networks and assay for the effects of these manipulations is in its infancy. This project will produce a series of strains unique in the detail in which the mapping between genetic mutations, regulatory effects and ecological consequences is understood. This understanding will contribute to the development of models that can predict how bacteria will evolve in response to particular selective pressures.
Almost all organisms must face and respond to challenges imposed by a dynamic external environment. Macroorganisms can choose to move to a better location. The small size of bacteria dictates a different strategy: they must stay and fight. Regulatory networks that connect an environmental input to an output – a change in gene expression – underlie this ability. We worked to quantitatively understand the connection between environment and a gene expression response by focusing on changes that occurred in the control of a small group of lac genes that enable the bacterium Escherichia coli to use a specific sugar, lactose. We found that evolution of E. coli in environments containing lactose led to specific and reproducible change in the regulation of these genes; they turned on faster and to higher levels than they did in the ancestral bacteria. We were able to find the genetic changes that led to these changes in regulation and show that, by themselves, they conferred fitness benefits. Extending this work to a wider range of E. coli strains, we found that lac gene regulation differed dramatically between strains, perhaps reflecting differences in their selective history. Moreover, these differences were only partly maintained when the genes were transferred into our original lab strain, indicating that their regulation reflects a combination of effects within the lac genes themselves and between the lac genes and the wider genetic background.
