Next generation infra-red glucose biosensors

葡萄糖是微生物的关键代谢产物，是更复杂的生物体最重要的能量来源，也是植物光合作用的关键产物。因此，在生物科学中，能够准确地绘制活生物和细胞中的葡萄糖浓度图以及医学中的葡萄糖浓度是至关重要的，因为在医学中，监测患者的血糖水平至关重要，特别是在糖尿病等疾病中。为医院常规使用的血糖监测设备提供动力的技术是电化学技术，需要侵入性物理采样。新的传感器技术正在开发中，它使用光来测量葡萄糖浓度。它的工作原理是使用一个荧光分子探测器，该探测器结合葡萄糖并改变荧光发射的光的颜色。这些生物传感器完全由蛋白质组成，因此甚至可以在生物体中自然表达。问题是，目前这些生物传感器使用的是被组织吸收的可见光波长。该项目将开发使用红外线荧光团的下一代葡萄糖生物传感器。这些波长的光更容易穿过组织和生物体，使生物传感器技术与许多其他常用的光学显微镜技术兼容。将测试不同的红外线荧光团，并将开发一系列对不同葡萄糖浓度敏感的生物传感器，以最大限度地适用于不同的生物问题。生物传感器将在试管中进行测试，但也将在活细胞中进行测试，包括模型酵母和哺乳动物细胞系。活细胞实验将使用标准的共聚焦显微镜和荧光显微镜，也将使用尖端的超分辨率和单分子显微镜。将使用简单的软件分析数据，并有机会使用MatLab和开发新的软件工具。将提供广泛的培训，包括分子克隆、蛋白质设计、生产和纯化、生物传感器设计以及显微镜和图像分析。因此，这个项目将适合各个科学领域的不同背景。这是一个高度跨学科的项目，有可能在生物科学中产生真正的影响，也有可能在患者血糖监测中应用于医学。

Glucose is a key metabolite for microorganisms, the most important energy source in more complex organisms and the key product of photosynthesis in plants. It is therefore crucial across the biological sciences to be able to accurately map glucose concentrations in living organisms and cells, as well as in medicine, where monitoring patient glucose levels is vital, particularly in diseases like diabetes. The technology powering blood glucose monitoring devices used routinely in hospitals is electro-chemical, requiring invasive physical sampling. New sensor technology is in development which uses light to measure glucose concentrations. It works using a fluorescent molecular probe which binds glucose and changes the colour of fluorescently emitted light. These biosensors are entirely made of protein so can even be expressed natively in the organism. The problem is that currently these biosensors use visible wavelengths of light which are absorbed by tissues. This project will develop the next generation of glucose biosensors using infra-red fluorophores. Light at these wavelengths passes through tissues and organisms much more easily and makes the biosensor technology compatible with many other commonly used optical microscopy techniques. Different infra-red fluorophores will be tested and a range of biosensors sensitive to different glucose concentrations will be developed to maximise applicability to different biological problems. Biosensors will be tested in test tubes but also in live cells, including model yeast and mammalian cell lines. Live cell experiments will use standard confocal and epifluorescence microscopy but also cutting-edge super resolution and single-molecule microscopy. Data will be analysed using simple software, with the opportunity to use Matlab and devlop new software tools. Extensive training will be provided, including molecular cloning, protein design production and purification, the design of biosensors, as well as microscopy and image analysis. Thus this project would suit a range of different backgrounds across the sciences. This is a highly interdisciplinary project with potential for real impact in the biological sciences and also potential medical application in patient glucose monitoring.