Decoding the Complex Cellular Information Flow by Multiplexed Chemosensing

这个项目将显著提高我们对复杂环境线索中细胞信息流的理解。细胞通过一系列事件对外界刺激做出反应，这些事件涉及在不同尺度上传递信息的信使元件。尽管在揭示单个信号通路方面取得了进展，但大多数信号转导由多个通路共享的事实挑战了我们目前对细胞信息流的理解。与电信系统相比，信元是在交织的信令网络中处理海量信息的优秀的多路复用器(MUX)和解复用(DEMUX)设备。特别是，作为最多任务的信使元件之一，细胞内钙参与细胞功能的许多方面。然而，现有的信息路由模型要么在钙信号中的适用性有限，要么可能低估了其信息容量。受他最近关于集体化学传感过程中钙稳态的发现的启发，PI假设胞内钙的非线性动态允许哺乳动物细胞在单细胞和多细胞水平上编码复杂的信息。PI建议通过研究基因工程模型细胞系的多重化学传感来检验这一假设。作为PI理解细胞信息处理物理的长期目标的重要一步，该项目不仅将提供对钙中介MUX/DEMUX机制的洞察，还将为实现其构建基于细胞的生物传感器和生物计算单元的工程潜力铺平道路。国际和平研究所将开发一个与研究计划紧密结合的多样化的教育和推广计划。具体地说：(I)利用俄勒冈州立大学(OSU)现有的项目，PI将设计一系列基于实验室的研究培训项目，以吸引女性和少数族裔高中生、暑期本科生实习生以及为撰写论文而工作的高年级本科生。(2)该项目产生的成果和数据将用于编制从2014年冬季起在俄勒冈州州立大学开设的定量生物学课程。本课程旨在从信息处理的角度讨论生物系统。(Iii)工业外展将受益于国际和平协会现有的工业伙伴关系和拟议的外展活动，例如实地考察和研究生实习，以传播研究成果。该项目由物理系的生命系统物理学方案和分子和细胞生物科学系的细胞动力学和功能方案共同支持。

This project will significantly improve our understanding of cellular information flow in the presence of complex environment cues. Cells respond to external stimuli through a cascade of events involving messenger elements that transduce information at diverse scales. Despite the progress in revealing individual signaling pathways, the fact that most signal transducers are shared by multiple pathways challenges our current understanding of cellular information flow. Compared to telecommunication systems, cells are excellent multiplexing (MUX) and demultiplexing (DEMUX) devices handling huge amount of information within an interweaving signaling network. In particular, as one of the most multitasking messenger elements, intracellular calcium engages in many aspects of cellular functions. However, existing models of information routing have either limited applicability in calcium signaling or may underestimate its information capacity. Inspired by his recent findings of the calcium homeostasis during collective chemosensing, the PI hypothesizes that the non-linear dynamics of cytosolic calcium allows mammalian cells to encode complex information on both the single cell and multicellular levels. The PI proposes to test the hypothesis by studying the multiplexed chemosensing of a genetically engineered model cell line. As an essential step of the PI's long term goal to understand the physics of cellular information processing, the project will not only provide insight to the calcium-mediate MUX/DEMUX mechanisms, but also pave the way of realizing its engineering potential to build cell-based biosensors and biocomputational units. The PI will develop a diverse educational and outreach program that is closely integrated with the research program. Specifically: (i) Utilizing existing programs at Oregon State University (OSU), the PI will design a series of lab-based research training projects to engage female and minority high school students, summer undergraduate interns as well as senior undergraduate students working toward their thesis. (ii) Results and data generated in the project will be used to develop quantitative biology curricula to be offered at OSU from the winter term of 2014. This class is designed to discuss biological systems from information processing perspectives. (iii) Industrial outreach will benefit from the PI's existing industrial partnership and the proposed outreach activities, such as site visits and graduate student internships to disseminate the research outcomes.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Cellular Dynamics and Function Program in the Division of Molecular and Cellular Biosciences.