Decoding the Complex Cellular Information Flow by Multiplexed Chemosensing

该项目将显著提高我们对复杂环境中细胞信息流的理解。细胞对外界刺激的反应是通过一系列涉及信使元素的事件来进行的，这些信使元素在不同的尺度上传递信息。尽管在揭示单个信号通路方面取得了进展，但大多数信号转导子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，信元是在交织信令网络中处理大量信息的优秀复用（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传导中具有有限的适用性，要么可能低估其信息容量。受他最近集体化学传感过程中钙稳态研究结果的启发，PI假设胞质钙的非线性动力学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假设。作为PI了解细胞信息处理物理学的长期目标的重要一步，该项目不仅将提供对钙介导的MUX/DEMUX机制的洞察，还将为实现其工程潜力铺平道路，以构建基于细胞的生物传感器和生物计算单元。PI将制定一个与研究计划紧密结合的多样化教育和推广计划。具体而言：利用俄勒冈州州立大学的现有方案，PI将设计一系列基于实验室的研究培训项目，以吸引女性和少数民族高中生、暑期本科实习生以及正在撰写论文的高年级本科生。(ii)该项目产生的结果和数据将用于开发从2014年冬季学期起在俄勒冈州立大学提供的定量生物学课程。这门课的目的是从信息处理的角度讨论生物系统。(iii)工业推广将受益于PI现有的工业伙伴关系和拟议的推广活动，如现场访问和研究生实习，以传播研究成果。该项目由物理学系的生命系统物理学项目和分子与细胞生物科学系的细胞动力学和功能项目共同支持。

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.