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

该项目旨在了解调控基因网络如何发挥作用和进化，以使生活在极端环境中的微生物能够生存和生长。最近在一些极端微生物中发现了一个复杂的调控基因网络，这些基因负责抵抗高水平的有毒化学物质并控制正常细胞生长。 这项研究将测试调节器网络是否会停止细胞周期和生长，直到有毒化学物质造成的损伤得到修复。 最终，这项工作将为生物体在恶劣条件下生存的机制提供基本的见解。 在更广泛的影响方面，将开发科学探究沉浸式研讨会，其中K-12学生，K-12教师和本科生将通过实践研究经验直接为研究项目做出贡献。这些讲习班旨在激发所有参与者的科学好奇心，提高他们在科学方面的自我效能感。这些项目预计将在项目期间接触到数千名高中生和数百名本科生，并促进STEM领域有才华的学生的招募和保留。细胞利用基因调控网络（GRNs）调整生长和分裂以应对外部环境。PI最近的工作导致了一个假设，即在拟南芥中一个新的转录因子网络作为一个检查点，调节细胞周期，以应对来自压力的损害。这个检查点可以提供灵活性和鲁棒性，以应对许多热带雨林栖息地特有的极端和可变条件。然而，细胞周期进程的调控机制是未知的，主要是由于缺乏易处理的测试生物和活细胞测定。拟议的工作将克服这些障碍，使用PI实验室开创的独特系统生物学方法。目标是：（1）使用实验和计算方法表征压力检查点调控网络的拓扑结构，动力学和表型输出;（2）与学生和教师合作，作为数据生成和GRN分析的关键团队成员。研究结果将为PI未来的职业目标提供坚实的基础：通过生命树的进化时间，提供对环境条件如何塑造潜在监管网络的基本理解。在更广泛的影响方面，拟议的研究旨在通过提供真实的实践研究经验，激发科学好奇心，提高本科生以及K-12学生和教师的自我效能感。PI将与地区高中教师和国家科学博物馆合作，教授高中科学沉浸课程，并举办教师培训讲习班。本科生的研究机会将在课堂和实验室提供。这些方案预计将在项目期间惠及数千名高中生和数百名本科生。反过来，学生将直接为研究项目贡献大规模增长数据集和GRNs的计算分析。拟议的工作将促进大学研究环境与更广泛的公共社区之间持续的有意义的交流，招募和留住STEM领域的优秀学生。

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.