Engineering principles of chemotaxis signalling pathways

在过去的几十年里，大量的生物学数据已经积累起来，这些数据集中在单分子的特性和由于基因操作导致的细胞形态的质变上。然而，人们对细胞内潜在生物通路的工程原理知之甚少，例如，完整的通路是如何工作的，它们处理什么类型的信号，它们如何处理噪声，以及它们是为了什么而优化的。趋化途径是细胞如何处理环境信息以感知并向化学物质移动的模型。特别是，大肠杆菌的趋化途径是任何生物体中极少数完全表征的信号通路之一。我们已经开始开发计算工具，通过模拟细胞“输出”到定义良好的“输入”的实验数据，例如环境中化学物质的变化，来理解完整的通路是如何处理信号的。我们对高等单细胞生物和免疫系统细胞的趋化途径知之甚少。然而，细胞能够对环境中化学物质的微小变化做出反应，这一点已经得到了很好的证实。从理论上讲，化学感受器在细胞表面的分布对这种高灵敏度至关重要。基于新的高分辨率成像技术，这些受体分布对各种生物体进行了定性。我们已经开始发展一种理论，即如何通过细胞表面受体精确地测量化学物质。我们将扩展这种方法，以获得最准确测量化学品的最佳受体分布。

A vast amount of biological data has been accumulated over the last few decades focusing on properties of single molecules and qualitative changes in cell morphology due to genetic manipulation. However, very little is known about the engineering principles of the underlying biological pathways inside cells, i.e. how complete pathways work, what types of signals they process, how they deal with noise, and what they are optimized for. The chemotaxis pathways are a model for how cells process information about their environments to sense and move towards chemicals. In particular, the chemotaxis pathway in the bacterium E. coli is one of the very few fully characterized signalling pathways in any organism. We have begun to develop the computational tools for understanding how the complete pathway processes the signals by modelling experimental data of the cell's 'output' to a well-defined 'input', e.g. to a change of a chemical in the environment. Much less is known about the chemotaxis pathways in higher single-cell organisms and cells of our immune system. However, it is well established that cells are able to respond to tiny changes of chemicals in their environment. From a theoretical standpoint the distribution of chemoreceptors on the cell surface is crucial for this high sensitivity. These receptor distributions are qualitatively known for various organisms based on new high-resolution imaging techniques. We have begun developing a theory of how accurately chemicals can be measured by cell-surface receptors. We will extend this method to obtain the optimal receptor distribution for the most accurate measurement of chemicals.