A surface plasmon resonance facility for label-free analysis of biomolecular interactions
A surface plasmon resonance facility for label-free analysis of biomolecular interactions
批准号:
BB/S019529/1
负责人:
Edward Tate
金额:
$23.28万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2019
资助国家:
英国
项目状态:
已结题
起止时间:
2019 至 --
中文摘要
分子水平上的生命依赖于大量亲密的、可逆的相互作用。在蛋白质等大分子的情况下,这些相互作用负责形成大型多亚基复合物,如稳定合成我们的遗传物质(DNA和RNA聚合酶)和我们体内所有蛋白质(核糖体)所需的机器。其他的接触对于稳定肉眼可见的结构是必要的,比如我们头发和指甲中的角蛋白,或者作为柔性支架支撑不同组织的胶原纤维。其中一些相互作用是短暂的,持续不到一秒,而另一些则有更长的寿命。确定这些相互作用的强度和速度对于确定它们的生物相关性至关重要,例如了解细胞如何组装我们的身体,产生能量和对抗不同类型的感染。这些信息也是重要的农业、生物技术、医学和工业应用的基础。例如,现代农业化学品和药物设计涉及开发一种特定的配体(充当“钥匙”),它调节我们细胞中的蛋白质(充当“锁”)。从一个结合力差的“钥匙”开始,需要用新的化学实体进行修饰和结合分析,以获得识别所需“锁”的改进版本-从而产生我们最终在市场上看到的药物化合物。表面等离子体共振(SPR)是目前精确测量这些相互作用的金标准技术。我们的目标是用最新的SPR设备取代伦敦帝国理工学院的过时设备,使研究人员能够利用这项技术加快他们的研究。
英文摘要
Life at the molecular level relies on a multitude of intimate, reversible interactions. In the case of macromolecules like proteins, these interactions are responsible for the formation of large multi-subunit complexes, like those that stabilise machineries required to synthesise our genetic material (DNA and RNA polymerases) and all proteins in our body (ribosomes). Other contacts are necessary to stabilise structures that are visible to the naked eye, like the keratin in our hair and nails or the collagen fibres that serve as a flexible scaffold to support different tissues. Some of these interactions are transient, lasting less than a second, whereas others have much longer lifetimes. Determining the strength and the speed of these interactions is essential to identify their biological relevance, e.g. to learn how cells assemble our bodies, generate energy and combat different types of infections. This information is also the basis of important agricultural, biotechnological, medical and industrial applications. For example, modern agrochemical and drug design involves development of a specific ligand (acting as a 'key') that modulates a protein in our cells (acting as a 'lock'). Starting with a poorly binding 'key', cycles of modification with new chemical entities and binding analyses are required to obtain improved versions that recognise a desired 'lock' - leading to compounds that we eventually see as drugs in the market. Surface plasmon resonance (SPR) is currently the gold-standard technique to accurately measure these interactions. Our aim is to replace obsolete equipment at Imperial College London with the latest SPR equipment to allow researchers to accelerate their investigations with this technology.
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