Interplay of Transcriptional, Translational Regulatory Mechanisms and Kinetics of an Environmental Response

智力优势：环境因素的变化具有可重现性。虽然氧气的变化可能在几秒钟到几分钟内发生，但温度变化的速度在几小时到几天之间要慢得多。生物体中的调控网络通过进化来调节，以引起与给定环境因素的特征相匹配的反应(例如，对快速变化的因素的快速反应)。该项目的主要假设是，在信息处理的不同阶段(转录、转录后、翻译和翻译后)调节的相对使用由环境反应的必要特征决定。为了在不同的环境条件下验证这一假设，将测量盐生盐杆菌菌株中所有转录本和蛋白质的合成和降解率的变化。在此概念验证的基础上，该研究项目将在特定环境响应的背景下，系统地调查不同级别的监管之间的相互作用。BROADER影响：资源：这项研究将产生跨不同级别的监管的基本原则，还将产生创新的计算和实验方法，这些方法将作为有良好记录的开放源代码数据和软件发布。教育：跨学科科学的快速发展正在扩大生物学教学方式和实践方式的差距。该实验室获奖的高中(HS)教育项目正在通过基层的探究式教学实践来弥合这一鸿沟。这项已有十年历史的计划主要针对弱势背景学生的暑期实习，鼓励他们通过许多伙伴关系申请，包括市中心青年计划和威斯康星州大学的提高妇女科学地位计划。通过该计划开发的教育工具包已经与州标准保持一致，通过课堂试点反复改进，并通过专业教师发展传播到美国14个州。除了在系统生物学方面培训博士后研究员外，该项目还将开发以探究为导向、基于标准的HS教材。这个新的课程模块是与当地科学教育工作者共同开发的，应教师的要求，将帮助学生内化使用系统生物学的概念和方法，以在环境变化的背景下理解细胞动力学。这些课程将与新的下一代科学标准保持一致，并通过严格的评估计划定期评估其对学生学习和职业选择的影响。

INTELLECTUAL MERIT: Environmental factors change with reproducible characteristics. While changes in oxygen can happen within seconds to minutes, temperature changes occur at a much slower pace over hours to days. Regulatory networks in an organism are tuned through evolution to elicit a response that matches the characteristics of a given environmental factor (e.g. a rapid response to fast changing factors). The overarching hypothesis of this project is that the relative use of regulation at different stages of information processing (transcriptional, post-transcriptional, translational and post-translational) is dictated by the necessary characteristics of an environmental response. In order to test this hypothesis under varying environmental conditions, changes in synthesis and degradation rates will be measured for all transcripts and proteins in strains of Halobacterium salinarum. Building in this proof-of-concept, the research project will systematically investigate interplay across different levels of regulation in the context of specific environmental responses.BROADER IMPACTS:Resources: This research will generate fundamental principles of integration across different levels of regulation, and also generate innovative computational and experimental methodology that will be published as well-documented, open-source data and software. Education: Rapid advances in interdisciplinary science are widening the gap in the way biology is taught and how it is practiced. An award winning high school (HS) education program in the lab is bridging this divide through inquiry-based teaching practices at the grassroots. This ten-year-old program is centered on summer internships for students of disadvantaged backgrounds who are encouraged to apply through numerous partnerships including programs for inner city youth and a UW-based program for advancement of women in science. Educational kits developed through this program have been aligned with state standards, iteratively improved through classroom pilots, and disseminated through professional teacher development to 14 states across the US. In addition to training postdoctoral fellows in systems biology, this project will also develop inquiry-driven, standards-based, HS educational materials. Developed together with local science educators, this novel curriculum module has been requested by teachers and will help students internalize the concepts and methods for using systems biology to understand cellular dynamics in the context of environmental change. These curricula will be aligned with the new Next Generation Science Standards and regularly assess its impact on student learning and career choices through a rigorous evaluation program.