Bacteria are rewriting their own genetic instruction manuals from scratch, creating new regulatory genes out of DNA that previously had no function. This matters because bacteria adapt to new environments—including antibiotic-laden hospitals or changing ocean temperatures—by rewiring their gene regulatory networks. Scientists understand how bacteria modify existing genes or steal new ones from other microbes, but they know almost nothing about how entirely new regulatory genes emerge from non-coding DNA. This project will track that process in real time, using molecular genetics, biochemistry, and experimental evolution to watch novel regulators appear, test what they do, and see how they evolve within larger networks. If successful, the work will reveal the environmental conditions and molecular constraints that allow bacteria to invent new regulatory interactions. That knowledge could help predict which bacterial strains are likely to become pathogens, guide the development of novel antimicrobials that target regulatory networks rather than killing cells outright, and improve models of how microbes will respond to climate-driven changes in soil and ocean ecosystems. The research is fundamental science—it asks how evolution works at the molecular level—but understanding the rules of regulatory innovation could eventually give researchers a practical tool for anticipating bacterial behaviour before it becomes a problem.
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The need to better understand and predict how bacteria evolve in response to environmental change is becoming more urgent. Antibiotic resistance is emerging at an alarming rate, and how microbes adapt to global changes will have lasting impacts on soil and ocean ecosystems as well as agricultural practices, conservation efforts, and the emergence of novel bacterial pathogens. Numerous studies now show that gene regulatory network evolution is an essential part of bacterial adaptation to novel ecological niches, yet, how the selective environment affects the emergence and evolution of gene regulatory networks remains understudied. Most work investigating the origins of regulatory circuitry has primarily focused on horizontal gene transfer and recombination events, and most evolution studies have examined adaptation via point mutations in pre-existing genes, often within a single environment or defined set of conditions. This proposal seeks to address these limitations by combining in vivo molecular genetics, in vitro biochemistry, multi-omics approaches, and experimental evolution to comprehensively assess and compare how environmental changes impact (i) the de novo emergence of novel regulators from previously non-genic DNA, (ii) the function of novel regulatory interactions, and (iii) the evolutionary trajectory of novel regulatory interactions and the overall networks in which they are contained. These findings will improve our understanding of the environmental and mechanistic constraints governing the de novo formation of novel regulatory interactions and their evolution within larger regulatory networks, with implications for predicting microbial adaptation to new ecological niches, developing novel antimicrobials, and combatting the emergence of new human pathogens.
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