Modelling drug binding to biological ion channels

在生物系统中，离子通道蛋白位于细胞膜上，有选择地允许特定类型的离子通过，从而产生电流。离子电流对许多生物过程都很重要，例如：调节细胞内的离子浓度；传递信号（如神经冲动）；或者协调肌肉的收缩（骨骼肌以及心脏、隔膜、肠道、子宫等）。我们一直在开发新的实验设计，以提供更多关于药物如何与离子通道结合的信息，这些实验可能在自动化机器上进行。该项目将涉及计算生物物理建模（非线性ODE系统的有效数值解）；应用统计技术量化模型参数和模型方程/结构中的不确定性；还有一些湿实验室的电生理实验。我们将设计更多信息丰富的实验，以减少我们开发的模型中的不确定性，并与实验室密切合作，测试我们设计的实验并改进它们。

In biological systems ion channel proteins sit in cell membranes and selectively allow the passage of particular types of ions, creating currents. Ion currents are important for many biological processes, for instance: regulating ionic concentrations within cells; passing signals (such as nerve impulses); or coordinating contraction of muscle (skeletal muscle and also the heart, diaphragm, gut, uterus etc.). We have been developing novel experimental designs to provide more information about how drugs bind to ion channels from experiments that are possible to do on automated machines. This project will involve computational biophysical modelling (efficient numerical solution of nonlinear ODE systems); the application of statistical techniques to quantify our uncertainty in model parameters and model equations/structure; and some wet-lab laboratory electrophysiology experiments. We will design more information-rich experiments to reduce our uncertainty in the models we develop and work closely with labs to test out experiments we design and improve them.