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

邓迪的高通量生物层干涉测量法用于抗菌和相互作用研究。

• 批准号: BB/M012425/1
• 负责人: Frank Sargent
• 金额: $ 46.01万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM012425%2F1
• 关键词: throughput; bio; layer; interferometry; Dundee

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.

蛋白质是几乎所有对活细胞的生存至关重要的分子过程的中心，无论该细胞是一个自由的活微生物还是复杂动物中重要器官的一部分。细胞中不同蛋白质的数量和数量是惊人的，但为了成功地发挥其生物学功能，蛋白质必须与特定的蛋白质或化学伴侣相互作用。有时，与其他蛋白质形成更高级的复合物是所讨论的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、脂质或碳水化合物结合，然后才能发挥其生物学功能。理解蛋白质如何与其他分子相互作用是我们在分子水平上基本理解通信和信号的核心。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，一根微小的光纤线的尖端附着着一种感兴趣的蛋白质。当将该尖端浸入含有将与感兴趣的蛋白质相互作用的分子的溶液中时，纤维的光学性质发生变化，并且这可以由仪器记录。因此，生成的数据可以提供关于蛋白质如何运作的全新基本信息。另一方面，这种仪器也可以用于探索可能破坏蛋白质-蛋白质相互作用或完全停止蛋白质工作的不同化学物质。这种光纤非常小，可以一次排列96根光纤。然后，这些纤维可以在几分钟内浸入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。从这组简化的相互作用物中，可能会发现一些抑制目标蛋白活性的相互作用物。破坏关键细胞通路的所谓化学“抑制剂”在现代细胞生物学研究项目中至关重要，它们用于了解细胞生理学的基本方面。在邓迪，我们还希望使用这种仪器来寻找可能抑制微生物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。