Isobel Jackson Hirst

Developing new approaches and improved technologies for the study of membrane protein structure and mechanism (i-CASE)

About me

As part of my undergraduate degree in Biochemistry at Bristol Uni I completed a year in industry at Diamond Light Source, the UK’s national synchrotron. At Diamond, my research focused on the purification of a bacterial ABC transporter for structural studies using techniques such as X-ray crystallography and cryo-electron microscopy. During this research I became interested in the challenges of structural biology, particularly when studying membrane proteins, as their hydrophobicity necessitates the addition of a solubilising agent, most of which are not compatible with structural techniques. I was drawn to this research project at Leeds because it is investigating the causes of the challenges in cryo-EM with the aim of developing ways to minimise these, making the technique more usable for difficult proteins like the ABC transporter I was working on at Diamond.

My research

From bacterial enzymes that break down organic matter in the soil, to the haemoglobin that carries oxygen around our bodies, proteins carry out the processes essential to life on Earth. How a protein behaves and therefore how it carries out these processes is determined by its 3D structure. Single particle cryo-electron microscopy (cryo-EM) is a technique used to obtain near-native structures of proteins which allows us to understand their function. In the past decade, cryo-EM has undergone a ‘resolution revolution’ thanks to vast improvements primarily in microscope hardware and image processing software which have catapulted it into the limelight of structural biology. Today, one of the major challenges in cryo-EM is preventing damage to proteins during sample preparation for the microscope. The aim of my research is to improve our understanding of how proteins are affected by sample preparation and use this knowledge to allow us to study challenging proteins and improve the resolution of cryo-EM structures by developing sample preparation methods that are more controllable and reproducible.

Contact

LinkedIn: www.linkedin.com/in/isobel-jackson-hirst