NSF Award
2427099
Microbes called archaea live in the most extreme places on Earth, such as boiling hot springs, saturated salt lakes, and deep-sea vents, and are models for how organisms survive in harsh environments on this planet and perhaps others. This research project will reveal the genetic blueprint for survival under certain extreme conditions. This project will also provide students with a research experience that emphasizes mathematical modeling and experimental approaches; these skills are important for future participation in the STEM workforce. <br/><br/>The overarching goal of this project is to understand how extreme environments select for regulatory network architecture and function. Transcription regulatory networks (TRNs) vary gene expression dynamically in response to stress. Such expression adapts physiology to improve fitness, leading to phenotypic diversity over evolutionary time scales. TRNs can “rewire” by mutations in cis-regulatory elements or trans factors such as transcription factors (TF). However, it remains unclear how genetic mechanisms underlie rewiring, how extreme forces select for new TRN arrangements, and whether rewiring is adaptive. These questions remain unresolved across life, but are especially understudied in the domain of life Archaea. Haloarchaea provide a unique model for investigating the evolution of TRNs under extreme forces given their experimental tractability in the lab and flexible adaptation to their hostile, unpredictable salt lake habitat (saturated salinity, temperature, solar irradiation, desiccation, starvation). Using a systems biology approach across three related species of haloarchaea, the PI discovered extensive rewiring of TRNs that make cellular decisions such as nutrient choice and stress response. This research has led to the hypothesis that extreme conditions select for more highly interconnected or complex TRNs, enabling rapid physiological adjustment in response to variable environments. The idiosyncrasies of haloarchaeal genomes, including differential TF protein family expansion and genomic plasticity may drive novel mechanisms of network rewiring, enabling niche expansion in surprisingly few generations. To test the generality of this hypothesis, the following research plan will greatly expand upon the previous research to learn the rules of life for TRN rewiring under extreme duress. The objectives are: (a) use genetics, genomics, quantitative phenotyping, and statistical modeling to compare TRN architecture and dynamical function across five species of halophiles (subnetworks and genome-scale, Objective 1); (b) force TRN rewiring with in-lab evolution experiments to observe molecular evolution in real time (Objective 2). This approach combines, yielding rapid and unprecedented insight into the dynamic function of archaeal regulatory networks and their impact on cell physiology.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
