CAREER: Elucidating cell cycle regulatory networks across the tree of life.

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This project seeks to understand how networks of regulatory genes function and evolve to allow microorganisms that live in extreme environments to survive and grow. A complex network of regulatory genes that are responsible for resistance to high levels of toxic chemicals and for control of normal cell growth was recently discovered in a number of these extreme microorganisms. This study will test whether the network of regulators stops the cell cycle and growth until damage from toxic chemicals is repaired. Ultimately, this work will provide fundamental insights into the mechanisms that organisms use to survive under inhospitable conditions. In terms of broader impacts, science inquiry immersion workshops will be developed in which K-12 students, K-12 teachers and undergraduates will contribute directly to the research project through hands-on research experiences. These workshops are intended to spark scientific curiosity and improve perceived self-efficacy in science for all participants. These programs are expected to reach thousands of high school students and hundreds of undergraduates during the project period, and to foster the recruitment and retention of talented students in STEM fields.Cells use gene regulatory networks (GRNs) to tune growth and division in response to the external environment. Recent work of the PI has led to the hypothesis that a novel network of transcription factors in Archaea functions as a checkpoint that regulates the cell cycle in response to damage from stress. This checkpoint may provide flexibility and robustness in response to extreme and variable conditions endemic to the habitats of many Archaea. However, regulatory mechanisms of cell cycle progress are unknown in Archaea, primarily due to the lack of tractable test organisms and live cell assays. The proposed work will overcome these obstacles using a unique systems biology approach pioneered in the PI's lab. The objectives are: (1) Characterize the topology, dynamics, and phenotypic output of the stress checkpoint regulatory network in Archaea using experimental and computational methods; (2) Collaborate with students and teachers as critical team members in data generation and GRN analysis. The research results will provide a firm foundation for the PI's future career goals: to provide a fundamental understanding of how environmental conditions shape the underlying regulatory network through evolutionary time across the tree of life. In terms of Broader Impacts, the proposed research aims to spark scientific curiosity and improve perceived self-efficacy of undergraduates as well as K-12 students and teachers by providing real hands-on research experiences. The PI will collaborate with area high school teachers and the state science museum to teach high school science immersion courses and implement teacher-training workshops. Undergraduate research opportunities will be offered in the classroom and lab. These programs are expected to reach thousands of high school students and hundreds of undergraduates during the project period. In turn, students will contribute large-scale growth datasets and computational analysis of GRNs directly to the research project. Work proposed will foster a continued meaningful exchange between the university research environment and the broader public community, recruiting and retaining talented students in STEM fields.