Single molecule analysis of chemotactic signaling system

(300趋化性是细胞感知化学梯度并对其作出定向反应的过程，在包括免疫、神经元模式化和形态发生在内的广泛的生物过程中起作用。趋化细胞如何从这些噪声信号中可靠地获取梯度信息是趋化性定向传感的关键问题，本研究发展了单分子成像技术，直接监测趋化信号系统中单个生物分子的行为。真核细胞趋化反应的单分子成像分析揭示了输入信号和信号转导过程的随机性。此外，我们已经开发了一个随机模型的趋化信号，其中噪声和信号传播沿着跨膜信号的趋化受体可以定量分析。从这些分析中获得的结果表明，第二信使产生反应的r ...更多信息 受体产生噪声信号，该噪声信号包含在该反应中固有产生的固有噪声和从配体-受体结合传播的外在噪声。这种内在和外在的噪音限制了趋化细胞的定向感知能力，这可以解释实验中观察到的趋化准确性对化学梯度的依赖性。我们的分析还通过分析受体和第二信使分子的随机特性如何改善或恶化趋化信号的信噪比（SNR），揭示了随机操作信号系统中信号改善的调节机制。我们的模型为趋化信号系统的实验方法提供了理论框架，并可以进一步应用于其他随机信号系统。此外，受生物处理的启发，其中生物体成功地获得噪声鲁棒性和信息处理的灵活性，我们提出了一种基于随机计算概念的随机计算方法。这将为基于传统计算原理的技术提供一种补充方法。少

(300 words)Chemotaxis, the process by which cells sense and respond directionally to chemical gradients, operates in a wide range of biological processes including immunity, neuronal patterning, and morphogenesis. How chemotactic cells reliably obtain information regarding the gradient from such noisy inputs is a critical question for directional sensing in chemotaxis.In this research, we have developed single molecule imaging techniques to monitor directly behaviors of individual bio-molecules in chemotactic signaling system. Single molecule imaging analysis of chemotactic response in eukaryotic cells revealed a stochastic nature in the input signals and the signal transduction processes. Also, we have developed a stochastic model of chemotactic signaling in which noise and signal propagation along transmembrane signaling by chemoattractant receptors can be analyzed quantitatively. The results obtained from these analysis reveal that the second messenger production reactions by the r … More eceptors generate noisy signals, which contain intrinsic noise inherently generated at this reaction and extrinsic noise propagated from the ligand-receptor-binding. Such intrinsic and extrinsic noises limit directional sensing ability of chemotactic cells which can explain the dependence of chemotactic accuracy on chemical gradients that have been observed experimentally. Our analysis also reveals regulatory mechanism for signal improvements in the stochastically-operating signaling system by analyzing how signal-to-noise ratio (SNR) of chemotactic singals can be improved or deteriorated by the stochastic properties of receptors and second messenger molecules.Our model provides a theoretical framework with experimental approaches to chemotactic signaling system and can further be applied to other stochastic signaling systems in general. Furthermore, inspired by biological processing, in which organisms manage successfully to acquire noise-robust characteristics and flexibility in their information processing, we proposed a stochastic calculation method based on the concept of stochastic computing. This will provide a complementary approach to technology based on conventional computing principles. Less