Structure, function, and evolution of gene regulatory networks in archaea

The broad goal of the Schmid lab is to understand how stress response mechanisms evolved. Archaea are the evolutionary progenitors of eukaryotes according to mounting phylogenomic evidence. Transcriptional regulation is required across life for surveillance and immediate response to stressful conditions. Transcription proteins, including transcription initiation proteins TATA binding protein (TBP) and Transcription Factor B (TFB), and histones, are strongly conserved across eukaryotes and archaea; however, it remains unclear in both domains of life how these proteins function together with other transcription factors (TFs) in transcription regulatory networks (TRNs) to sense and respond to stress. Moreover, how TRNs evolve under selective pressure from abiotic stress remains a major knowledge gap. Archaea dominate in stressful environments, where conditions vary between extremes of temperature, pH, and salinity. They are single-celled microorganisms that lack nuclei and complex posttranscriptional mechanisms. Together these features present an ideal, simplified model for understanding conserved mechanisms of transcriptional regulation in response to stress, and how those mechanisms evolve. Recent research in the Schmid lab discovered specific examples of TRN conservation and rewiring by comparing the architecture and dynamic function of TRNs across related species of hypersaline adapted archaea, or haloarchaea. Together, this research has led us to hypothesize that extreme and variable abiotic stress conditions select for more highly interconnected or complex TRNs, enabling rapid physiological adjustment in response to variable environments. To test this hypothesis, here we will use an integrated experimental and computational systems biology approach pioneered in the Schmid lab to characterize TRN architecture (how TFs interact with their target genes) and function (dynamical gene expression and phenotypic outcomes) across the entire archaeal tree. We will compare these TRNs with those in eukaryotes to determine how TFB/TBP function is conserved, and to detect patterns of TRN conservation vs rewiring across large evolutionary distances. We expect that the research results will yield fundamental insight into transcription mechanisms across domains of life.