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.
All current life forms on our planet are the products of natural evolution. Yet, we do not know how to predict or control natural evolution. This would be important not only to understand the origins of our biosphere, but also to determine how cells evolve. Learning about cellular evolution will teach us why cancer develops and why microbes resist antibiotic treatment. When cell evolve, their genes change. But which genes and how should they change? To study how specific genes change during evolution, in this project we focused on a handful of genes that cordinately control the response of Escherichia coli bacteria to the sugar lactose. We worked towards answering two questions: (1) How does gene regulation adapt to selection in novel environments? (2) What are the ecological and evolutionary consequences of gene evolution? To answer these questions we evolved Escherichia coli bacteria in the laboratory, in well-defined environments that included the sugars lactose, glucose, alternating lactose/glucose, or a mixture of the two. In the meanwhile, we measured the activity of lactose genes in single cells, and analyzed the data. We found multiple changes in lactose gene activity that depended on the conditions where cells evolved. These changes were associated not only with the lactose genes themselves, but also with DNA regions that control lactose genes. These mutations improved the growth of cells in specific environments, indicating that they are responsible for adaptation in each condition. Overall, we now understand better how evolution can change not only genes, but also their control in evolving cells. To further investigate the benefits of control, we altered the balance of activities for lactose gene products. We found that the inbalance of these gene products can cause some cells to stop growing, while some cells grow very fast, optimizing population growth. This suggests that cells may not adapt uniformly to certain conditions. Instead, they could adapt as a population, by sacrificing a small fraction of cells so that the rest of the cells can grow really fast. By involving students and postdoctoral postdoctoral researchers in this work, we trained them to understand computational and laboratory/experimental methods. We have presented our findings at national and international conferences, and we have published research papers that are freely accessible to anyone who would like to learn in more detail about our work.
