A Queueing Framework for Synthetic Circuits in E. coli

智力优势：生物细胞可以应对处理瓶颈，也可以利用瓶颈的动态来强有力地控制细胞行为。这一认识促使人们重新评估被认为支配生物电路的基本设计原则。这个项目将研究大肠杆菌中的合成和自然电路，这些电路已知经历了由于基本细胞成分(创建、修改或降解)对共享分子机制的竞争而产生的瓶颈。实验数据与理论预测相结合，将允许开发和验证与生物系统相关的排队理论原理。排队论通常被用来解决交通和通信系统中的性能限制。荧光显微镜、微流体学和合成生物学将与定量建模相结合，根据排队理论探索蛋白质在大肠杆菌中的降解机制和应激反应途径。这个项目的成功完成将导致有效的策略来合成和理解生物电路，从而避免或利用处理瓶颈来执行特定的任务。生物排队理论的成功演示可能还会影响更传统的学科，包括电信网络、呼叫中心和交通系统。广泛的影响：该项目的一部分将导致为小学STEM教育构建新的内容，特别强调科学的跨学科方面。这在很大程度上将通过与儿童科技大学(KTU)的密切合作来实现。KTU是弗吉尼亚理工大学的一个成功的小学项目，其唯一目标是“通过激发孩子们对这些领域的兴趣来创造未来的科学、技术、工程和数学(STEM)劳动力”。这种合作将导致产生、展示和分发互动摊位，以说明与该项目相关的跨学科现象。研究生和本科生将接受服务学习方面的指导，以确保有效的外展，并为这些学生提供教学经验。将支持本科生构建虚拟KTU模块，该模块免费向所有年龄段的学生和教育工作者提供基于网络的STEM主题互动演示。

Intellectual Merit: Biological cells can cope with processing bottlenecks and also leverage the dynamics of bottlenecks to robustly control cellular behavior. This realization prompts a re-evaluation of the fundamental design principles believed to govern biological circuits. This project will investigate synthetic and native circuits in E. coli that are known to experience bottlenecks stemming from the competition of basic cellular components (created, modified, or degraded) for the shared molecular machinery. The experimental data combined with the theoretical predictions will allow the development and validation of queueing theoretical principles relevant to biological systems. Queueing theory is commonly applied to resolve performance limitations in traffic and communications systems. Fluorescence microscopy, microfluidics, and synthetic biology will be combined with quantitative modeling to probe protein degradative mechanisms and stress response pathways in terms of queueing theory in E. coli. Successful accomplishment of this project will lead to effective strategies for the synthesis and understanding of biological circuits that either avoid or exploit processing bottlenecks to perform specific tasks. The successful demonstration of the biological queueing theory is likely to impact also the more traditional disciplines, including telecommunication networks, call centers and transportation systems.Broader Impacts: Part of this project will lead to the construction of new content for elementary school STEM education with a specific emphasis on the interdisciplinary aspect of science. This will be done largely through close collaboration with Kids' Tech University (KTU), a successful elementary school program at Virginia Tech with the single goal to create "the future workforce in science, technology, engineering, and mathematics (STEM) by sparking kids' interest in these fields." This collaboration will result in the generation, presentation, and distribution of interactive booths to illustrate interdisciplinary phenomena related to this project. Graduate and undergraduate students will be mentored in service learning to ensure effective outreach and to provide these students with teaching experience. Undergraduates will be supported to construct modules for Virtual KTU, which freely provides interactive web-based demonstrations of STEM topics to students of all ages and educators.