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

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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.