Adaptive Queueing in Intracellular Networks

点击翻译按钮获取中文摘要

Rapid and coordinated response to environmental fluctuations and the ability to maintain function in a broad range of conditions is a key to survival in the biological world. Therefore, organisms employ complex regulatory strategies that combine sensitivity and robustness in response to environmental changes. One potential mechanism for such responsiveness that has emerged through recent studies of enzymatic networks is a queueing effect in protein abundances. The phenomenon appears to be widespread in biology. This research project employs mathematical modeling and synthetic biology to explore and better understand this mechanism and its role in biological functions.This project investigates a queueing effect in intracellular networks. As processing enzymes transition from underloaded to overloaded conditions, the corresponding protein abundances (queues) increase drastically, and in a highly coordinated fashion. A number of recent observations suggest that enzymatic networks are often poised near the balance point between underloaded and overloaded regimes where it makes them highly sensitive and responsive to transient environmental fluctuations. This phenomenon appears to be widespread in biology; furthermore it should be highly optimized to a broad range of environmental conditions by adaptive regulatory mechanisms. In this project, the investigators combine rigorous mathematical analysis with quantitative computational modeling and synthetic biology to pinpoint the mechanisms and probe the role of adaptive queueing in the dynamics of small gene circuits as well as large intracellular enzymatic networks in bacteria and yeast. The investigators make use of their combined expertise in queueing theory, stochastic kinetic modeling, design of robust synthetic gene circuits and microfluidic technology to elucidate and characterize the role of adaptive queueing as a fast and flexible signal transduction and regulatory mechanism in bacteria and higher organisms.