Breaking down barriers to cause a paradigm shift in ultra-sensitive detection of protein structure.

这种跨学科的应用旨在打破将物理科学和生物学分开的人为障碍，并将允许开发和利用一种全新的革命性生物传感器技术。目前，生物传感器是相对迟钝的工具，可以感知特定感兴趣物质的存在。我们发现的这种现象为生物传感增加了另一个维度，不仅允许我们检测物质的存在，还可以感知其结构，并将使实时监测结构变化成为可能。这种独特的能力非常适合于感知和研究与蛋白质结构(构象)变化相关的常见疾病，如阿尔茨海默病？S、帕金森？S、传染性海绵状脑病、家族性淀粉样多发性神经病、亨廷顿？S病和II型糖尿病。这项技术源于我的实验室最近的一项发现，即具有固有的利手感觉的电场(即具有顺时针或逆时针的感觉)可以用来以令人难以置信的灵敏度检测生物大分子(生物大分子)的三维结构。这种现象比目前用于探测生物大分子结构的低分辨率方法(如CD和ORD)至少要灵敏一百万倍，并且可以检测纳米克材料。为了说明这项技术的潜在影响，申请者将研究在疾病中重要的动态蛋白质过程、蛋白质折叠/展开和纤维形成。

This discipline-hopping application is intended to break through the artificial barriers that separate the Physical Sciences and Biology and will allow the development and exploitation of an entirely new and revolutionary biosensor technology. Currently, biosensors are relatively blunt tools that can sense the presence of a specific substance of interest. The phenomenon we have discovered adds another dimension to biosensing, by not only allowing us to detect the presence of a substance, but also sense its structure, and will enable the monitoring of structural changes in real time. This unique capability is ideally suited to sensing, and studying, common diseases associated with changes in protein structure (conformation) such as: Alzheimer?s, Parkinson?s, transmissible spongiform encephalopathies, familial amyloid polyneuropathy, Huntington?s disease and type II diabetes. The technology derives from a recent discovery in my laboratories, that electric fields, which have an intrinsic sense of handedness (ie have a sense which is either clockwise or anticlockwise), can be used to detect, with incredible sensitivity, the 3-D structure of large biological molecules (biomacromolecules). The phenomenon is at least a million times more sensitive than low-resolution methods currently used to probe the structure of biomacromolecules, such as CD and ORD, and can detect nanograms of material. To illustrate the potential impact of the technique the applicant will study dynamic protein processes, protein folding / unfolding and fibrilation, which are important in disease.