Pushing the Speed Limits of High-Speed Atomic Force Microscopy

了解复杂分子的结构动力学对于提高我们对材料、医学和疾病的知识至关重要，然而，很少有技术可以捕获足够高的速度或分辨率的运动来了解潜在的行为。高速原子力显微镜(HS-AFM)使我们能够以亚纳米分辨率拍摄分子在液体环境中以每秒10帧的速度活动。然而，许多重要的动力学发生得比这快得多，新开发的AFM高度光谱模式允许以每秒100,000次的速度测量运动。高度光谱方法可用于研究多个分子的扩散或单个分子的结构动力学。在这个博士学位中，你将学习、利用和开发HS-AFM高度光谱技术，目的是突破目前的实验极限，在以前无法达到的时间和长度尺度上研究包括蛋白质在内的分子。为了进行这些实验，你将开发新的算法和分析方法，并应用理论和计算来获得关于单分子水平上的动力学行为的定量信息。你将应用这些方法与包括医学、生物学、物理和化学在内的多个领域的研究人员一起回答一些可能的生物物理和生物医学问题。

Understanding the structural dynamics of complex molecules is vital to advancing our knowledge of materials, medicine and diseases, yet there are few techniques which can capture motions at high enough speeds or resolution to understand the underlying behaviour. High-Speed atomic force microscopy (HS-AFM) allows us to video, with sub-nanometre resolution, molecules in action at 10 frames per second whilst in liquid environments. However, many important dynamics occur much faster than this, the newly developed height spectroscopy mode of AFM allows motions to be measured at 100,000 times per second. The height spectroscopy method can be applied to study the diffusion of many molecules or the structural dynamics of an individual molecule. In this PhD you will learn, utilise and develop HS-AFM height spectroscopy techniques with the aim to push past current experimental limits to study molecules including proteins at previously inaccessible time and length scales. To perform these experiments, you will develop new algorithms and analysis methods and apply theory and computation to obtain quantitative information about kinetic behaviour at the single molecule level. You will apply these methods to answer a number of possible biophysical and biomedical questions with researchers across multiple fields including Medicine, Biology, Physics and Chemistry.