Understanding Gene Regulatory Network Function During Stress Response Adaptation of an Archael Extremophile

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Understanding gene regulatory network function during stress response adaptation of an archaeal extremophileIntellectual merit: Although life science research has entered the post-genomic era, we still understand little about the diversity of microbial life on earth. Information is particularly lacking on microbial extremophiles, which thrive at the limits of life, in deep-sea hydrothermal vents under high pressure and temperature, saturated salt lakes, and polar icecaps. Many of these organisms are members of the third domain of life, the archaea. Although archaea contribute substantially to global carbon and energy cycles, they remain understudied because they are difficult to culture and genetically manipulate. How do these microorganisms cope with an extreme and changing environment? How do they alter their genetic programs and metabolic pathways to adapt and survive changes in their unique habitats on earth? These questions are particularly relevant today, as climate change rapidly alters the conditions that support life across the globe. The impact of such changes on the microbial communities responsible for global carbon and energy cycling is unclear, but is expected to have enormous implications for human society. To address these issues, the long-term goal of the proposed research is to understand how organisms maintain homeostasis in the face of fluctuating environmental conditions. Central to this process are gene regulatory networks (GRNs) composed of groups of regulatory proteins that switch genes on and off in response to environmental stimuli. Upon sensing a change in the environment, GRNs promote the production proteins that repair damage, restore the cell to a healthy state and prepare it for future stress conditions. The Halobacterium salinarum studied in this research thrives in high salt environments. This organism is a stress response specialist, capable of surviving in the Great Salt Lake during strong daily fluctuations of light, heat, oxygen, and nutrients at extreme salt concentrations. In response, the organism shifts its metabolism between four light- and oxygen-dependent energy-generating modes. The aim of the proposed work is to determine how the organism uses GRNs,or gene circuitries, to adapt to the dynamic alterations in light, oxygen, and nutrients to ensure survival. This research will employ an innovative systems biology approach, which combines cutting-edge high throughput experimental techniques with computational and statistical modeling. Halobacterium is a good model system for studying archaeal extremophiles because it is easy to culture and genetically manipulate. What we learn about the genetic circuitry of Halobacterium will be readily applicable toward mapping the genetic circuits of other archaea. Moreover, it will provide a deeper understanding of the dynamics of microbial GRNs and expression patterns in response to changing environmental conditions. More generally, the outcome of this research will lay the foundation for understanding microbial energy production and global carbon cycling in response to climate change. Broader impacts:The research will contribute to education, training, and outreach at the high school, undergraduate, and graduate levels. Specifically, students at all levels will have training opportunities at the interface of mathematics and biology. First, the PI and lab members will teach a week-long mini course for students from North Carolina School of Science and Math, a public high school in Durham, NC that draws the top students each year from each of the congressional districts in North Carolina. Second, outreach research opportunities associated with the project will be provided for undergraduates from North Carolina universities that serve underrepresented groups through established summer programs at Duke (e.g. North Carolina Central University, Fayetteville State University). Third, a graduate student funded on the project will receive next generation interdisciplinary training at the interface of mathematics and biology.