High throughput bio-layer interferometry at Dundee for anti-microbial and interaction studies.

蛋白质是几乎所有分子过程的中心，这些分子过程对活细胞的生存至关重要，无论细胞是自由活的微生物还是复杂动物重要器官的一部分。细胞中不同蛋白质的数量和数量是惊人的，但为了成功地执行它们的生物功能，蛋白质必须与精致特定的蛋白质或化学伙伴相互作用。有时，与其他蛋白质形成高阶复合体是上述生物过程的中心事件。有时，蛋白质根本不与其他蛋白质相互作用，而是与小分子或其他大分子如核酸、脂类或碳水化合物结合，然后才能发挥其生物学功能。了解蛋白质如何与其他分子相互作用，对于我们在分子水平上的基本理解、交流和信号传递是至关重要的。物理学家与生物学家、化学家和数学家合作，设计了许多测量和量化分子相互作用的技术。一种相对较新的技术被称为生物层干涉测量法。在这项技术中，一根细小的光纤线的顶端附着着一种感兴趣的蛋白质。当将这个尖端浸入含有与目标蛋白质相互作用的分子的溶液中时，纤维的光学性质会发生变化，这可以由仪器记录下来。因此，产生的数据可以给出关于蛋白质如何工作的全新的基本信息。另一方面，这种仪器也可以用于探索可能扰乱蛋白质-蛋白质相互作用或阻止蛋白质完全工作的不同化学物质。光纤非常小，一次可以排列成多达96根光纤的阵列。然后，这些纤维可以在几分钟内被浸泡在数百种不同的化学物质中，这样就可以在巨大的“化学图书馆”中搜索结合的随机分子。从这组缩小的相互作用因子中，也许可以找到一些抑制目标蛋白活性的因子。在现代细胞生物学研究项目中，破坏关键细胞通路的所谓化学“抑制剂”至关重要，在这些项目中，它们被用来了解细胞生理学的基本方面。在Dundee，我们还希望使用这台仪器来寻找可能抑制微生物新陈代谢关键过程的分子，从而帮助支持全球寻找新的抗微生物药物。

Proteins are at the centre of almost all the molecular processes that are important for the survival of the living cell, be that cell a free living microbe or part of a vital organ in a complex animal. The number and amount of different proteins in a cell is staggering but in order to successfully carry out their biological function, proteins must interact with exquisitely specific protein or chemical partners. Sometimes, forming a higher-order complex with other proteins is the central event to the biological process in question. Sometimes, proteins do not interact with other proteins at all but instead bind with small molecules, or other macromolecules such as nucleic acids, lipids or carbohydrates, before they can carry out their biological function. Understanding how proteins interact with other molecules is central to our basic understanding communication and signalling at the molecular level. Physicists, working in collaboration with biologists, chemists and mathematicians, have devised many techniques for measuring and quantifying molecular interactions. One relatively new technique is called bio-layer interferometry. In this technique a tiny fibre optic thread has a protein-of-interest attached to its tip. When this tip is dipped in a solution that contains a molecule that will interact with the protein-of-interest the optical properties of the fibre change and this can be recorded by the instrument. The data generated can therefore give brand new fundamental information on how proteins operate. On the other hand, this instrumentation can also be of use in exploring for different chemicals that might disrupt protein-protein interactions or stop a protein from working altogether. The optical fibres are so small that they can be arranged in arrays of up to 96 fibres at a time. The fibres can then be dipped in hundreds of different chemicals over the course of a few minutes and that way huge 'chemical libraries' can be searched for random molecules that bind. From that narrowed-down set of interactors, it may be possible to find some that inhibit the activity of the protein-of-interest. So-called chemical 'inhibitors' that disrupt key cellular pathways are of critical importance in modern cell biology research projects, where they are used to understand fundamental aspects of cellular physiology. At Dundee, we also wish to use this instrument to search for molecules that might inhibit key process in microbial metabolism - and so help underpin the global search for new anti-microbials.