This award, seeks fundamental understanding of how microorganisms gather nutrients and remain viable while facing the most extreme conditions on Earth. Many of these organisms reside in salt saturated lakes and ponds that are low in nutrients and limited for oxygen. These "halophiles", members of the domain Archaea, can teach us about the origins of energy metabolism since they exploit a wide array of metabolic strategies to survive on the same pool of scarce resources. These halophiles naturally synthesize unique chemicals, such as those resembling jet fuel and biodegradable plastic. Large gaps in knowledge regarding halophile metabolic functions have prevented the use of halophiles for alternative energy solutions. This project will fill these gaps by generating and comparing computational models of energy production pathways across 80 species of halophiles. Empirical measurements of metabolic products from two test species will be used to refine the model predictions. Each year, the PI's research group will teach two weeklong science immersion workshops, one for high school students and the other for undergraduates at University of Puerto Rico. In both workshops, students will measure and model halophile viability during extreme stress. This research will provide fundamental knowledge regarding the evolution of energy production, enable future alternative energy strategies, and engage a diverse population of students in STEM fields early in their careers.
The long-term goal of this project is to increase fundamental knowledge regarding how metabolic pathways of archaeal microorganisms are regulated in response to varying nutrients in the environment. Hypersaline-adapted Archaea, or halophiles, provide a unique model for investigating the co-evolution of the transcription regulatory and metabolic networks. Member species share a common hypersaline habitat, but exhibit extensive diversity in how they generate energy. Nutrients are intermittently available in hypersaline lakes during seasonal variations. In response, halophiles have acquired a wide array of possible metabolic solutions to survive on the same pool of scarce resources. Recent transcriptomic and metabolomics evidence from the PI's lab suggest that halophiles use transcriptional regulation as a primary mechanism to tune the metabolic network dynamically in response to nutrient fluctuations. Based on this evidence, the working hypothesis is that the regulatory network co-evolves with the metabolic network in diverse ways during nutrient fluctuation. However, to date, archaeal metabolic diversity has been largely unexplored due to the scarcity of tractable model organisms. Recently, 80 genome sequences of halophiles have become available, a scale that is unprecedented among Archaea. Using these genomic sequence data, the following objectives will be carried out to test the central hypothesis: (a) Construct and compare metabolic network models for 80 species of halophiles using automated computational methods; (b) Test model predictions regarding nutrient and genetic perturbations in two closely related, genetically tractable halophile model species; (c) Refine metabolic models using transcriptome and metabolome data as additional constraints.
