Information tranfer in NF-kappaB and MAPK pathways

描述(申请人提供)：细胞内信号转导通路是信息交流的途径，允许活细胞扫描其环境和内部状态，并对各种刺激做出适当的反应。这一功能以及基本生物化学的细节表明，对信号通路传递和处理的信息进行量化和分析可能是分析信号通路结构和信号响应敏感性的一个方便和信息丰富的框架。在这里，我们建议对信号转导通路中的信息传递和处理进行基于信息论的分析，重点是MAPK和NF-kappaB通路。我们建议将这些途径的数学、计算和实验研究的结果与开发通过生化反应和/或反应组(信号模块)的信息流的信息论处理相结合。一组初步结果表明，这一理论的发展是可行的，并可以带来一系列关于细胞信号转导的有趣和重要的见解。我们提出，在信令路径中传输的信息量可以用通常的单位(每单位时间的比特数)来估计，从而对信道容量、冗余度、信息编码和抗噪性进行了明确的定义。我们提出了如何将这些概念应用于两条特定且至关重要的信号转导途径，其中信息流是动态的，并且可以以空间分布和/或反馈的方式进行调节。总之，我们建议发展一个活细胞信号转导的数学信息理论，作为一个有别于更传统的数学和计算方法的理论分析框架，并与之互补。

DESCRIPTION (provided by applicant): Intracellular signal transduction pathways are routes of information communication allowing living cells to scan their environment and internal state and respond appropriately to various stimuli. This function, as well as the details of the underlying biochemistry, suggest that quantification and analysis of information passed and processed by signaling pathways might represent a convenient and informative framework for the analysis the signaling pathway structure and of the sensitivity of signaling response. Here we propose to develop an information theory based analysis of information transfer and processing in signal transduction pathways with a specific emphasis on the MAPK and NF-kappaB pathways. We propose to combine the results of mathematical, computational and experimental studies of these pathways with development of an information theoretical treatment of information flow through biochemical reactions and/or groups of reactions (signaling modules). A set of preliminary results suggest that the development of this theory is feasible and can lead to a series of interesting and important insights about cell signaling. We propose that the amount of information transmitted in signaling pathways can be estimated in the usual units (bits per unit time) leading to clear definitions of channel capacity, redundancy, information coding and noise resistance. We propose how these notions can be applied to two specific and vitally important signal transduction pathways, where the information flow is dynamic and may be regulated in a spatially distributed and/or feedback fashion. In summary, we propose to develop a mathematical information theory of signal transduction in living cells as a theoretical analysis framework distinct from and complementary to the more traditional mathematical and computational approaches.