We visualise biochemical processes in great detail in both space and time to learn more about the mechanisms that keep cells alive and healthy.
The molecules making up our cells all adopt specific structures so they can carry out their roles in a dynamic environment. Structural biology techniques allow us to image these molecules in great detail. Beyond the sheer excitement of glimpsing the elements of life, such studies enable the design of drugs. But current methods have one, near universal, limitation – they produce still snapshots rather than videos of biomolecules in action.
My lab is developing a method to produce such movies and gain understanding of cellular processes at an unprecedented level of detail. The videos we are all used to watching are made out of dozens of snapshots of the unfolding scene, taken each second. Similarly, to “film” biochemical reactions we let them proceed in bespoke miniature devices, which can pause them at multiple, precisely incremented points in time each second and allow us to take snapshots.
They do so by generating small droplets of the sample reaction that are then rapidly frozen and visualised using a powerful cryo-electron microscope and elaborate computer algorithms.
We are applying this method, alongside state-of-the-art imaging and biophysical techniques, to study new frontiers of biology. Our two major interests are how DNA is repaired when damaged and the regulation of a system within cells which removes old or faulty proteins, called the ubiquitin-proteasome system. These quality-control pathways are both essential for health and also prime targets of new cancer therapies.