Studying biology one molecule at a time by combining optical tweezers, fluorescence microscopy and microfluidics.

通过结合光镊、荧光显微镜和微流体技术，一次研究一个分子的生物学。

• 批准号: BB/T017554/1
• 负责人: Luca Pellegrini
• 金额: $ 58.16万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT017554%2F1
• 关键词: Studying; biology; molecule; time; combining

The purpose of our research proposal is to foster new and better ways to do science. We aim to empower scientists at the University of Cambridge and in the wider UK scientific community by giving them access to a new and important technology, that is transforming the way in which we design and carry out experiments.Traditionally, molecular biologists have learnt about the way molecules such as proteins and DNA work inside cells by examining samples that contain a very large number of the molecules under study. This type of 'biochemical reconstitution' experiments have been instrumental in providing us with the molecular picture of the cellular world that we now have.One important limitation of these experiments is that, because they consider a large population of the molecule under study, they can only tell us about its average properties over time. However, important aspects of molecular behaviour can only be understood when the molecules are considered individually. Important examples include how ATPase synthase, the enzyme that generates the energy-rich molecule ATP, works and how flagella propel bacteria forward, helping them swim in a purposeful way. The instrument that we intend to acquire is akin to a set of tweezers to manipulate very tiny objects. To be able to handle something as small as a single molecule accurately and precisely, the tweezers are controlled by by laser light, hence the instrument name as 'optical tweezers'. By being able to grip and probe individual molecule with the tweezers, we can probe and understand their mechanical properties, which are important to determine the way molecules behave inside the cells.The scientific applications of this new technology are very wide, and include understanding how proteins that protect our genome from damage interact with DNA, and how cells transport their protein cargoes from one organelle to another. In turn, such knowledge can be eventually exploited to understand what happens to us when such important cellular processes are disrupted in disease, and how to design rational strategies to intervene therapeutically.

我们研究计划的目的是培育新的、更好的科学研究方法。我们的目标是让剑桥大学和更广泛的英国科学界的科学家能够接触到一项重要的新技术，这正在改变我们设计和进行实验的方式。传统上，分子生物学家已经了解了通过检查含有大量所研究分子的样本，了解蛋白质和 DNA 等分子在细胞内的工作方式。这种类型的“生化重建”实验有助于为我们提供我们现在拥有的细胞世界的分子图景。这些实验的一个重要限制是，因为它们考虑了所研究的分子的大量群体，所以它们不能只告诉我们它随时间变化的平均特性。然而，只有单独考虑分子时才能理解分子行为的重要方面。重要的例子包括 ATP 合成酶（一种产生富含能量的分子 ATP 的酶）如何工作，以及鞭毛如何推动细菌前进，帮助它们有目的地游泳。我们打算购买的仪器类似于一把镊子，可以操纵非常小的物体。为了能够精确地处理小至单个分子的物体，镊子由激光控制，因此仪器被称为“光镊”。通过用镊子夹住和探测单个分子，我们可以探测和了解它们的机械特性，这对于确定分子在细胞内的行为方式非常重要。这项新技术的科学应用非常广泛，包括了解如何保护我们的基因组免受损伤的蛋白质与 DNA 相互作用，以及细胞如何将其蛋白质货物从一个细胞器运输到另一个细胞器。反过来，这些知识最终可以用来了解当如此重要的细胞过程在疾病中被破坏时我们会发生什么，以及如何设计合理的策略来进行治疗干预。