About the Project
This is an exciting project developing techniques in time-resolved structural biology at the frontiers of cryo-electron microscopy (cryoEM).
Understanding how macromolecular complexes assemble and function as molecular machines is essential for revealing the molecular principles that govern biological systems. CryoEM is a powerful tool for structural analysis of such complexes, enabling high‑resolution characterisation of molecules trapped in different conformational states. However, how these states are related to one another over time and how conformational changes drive function remains poorly understood.
Time‑resolved cryoEM allows the chronological analysis of these dynamic biological processes to fully understand the mechanism of action. The Midlands Regional CryoEM Facility (University of Leicester) has recently purchased the first commercially available Speed Blot system, a cutting‑edge technology designed to enable rapid sample preparation for the time-dependent capture of intermediates in reactions occurring on millisecond timescales.
In this PhD project, we aim to further develop and apply this technology to investigate the dynamic mechanisms of large molecular machines. Initially, the project will focus on capturing transient intermediate states in DNA-repair machinery. This is a collaboration with Dr Amanda Chaplin who is an expert on non-homologous end-joining DNA repair. Dr Chaplin will be a member of the supervisory committee. Other projects with researchers in the Leicester institute for Structural and Chemical Biology (LISCB) will also be developed.
You will have direct access to a world class CryoEM Facility, which includes a dedicated low humidity laboratory for sample preparation, a ThermoFisher Scientific Titan Krios electron microscope with Gatan K3 direct detector and a bespoke computational cluster for data analysis. During this PhD you will gain extensive experience in cryoEM including sample preparation, microscope operation and computational analysis. You will develop time-resolved methodologies for cryoEM sample preparation and collaborate with scientists on a variety of topics to ask important, biologically relevant molecular questions.
21st September 2026 or 1st October 2026 start preferred.
Project enquiries to Dr Amanda Chaplin ac853@le.ac.uk
To apply please refer to the information on our web page https://le.ac.uk/study/research-degrees/funded-opportunities/cls-liscb-mcb-chaplin
https://le.ac.uk/study/research-degrees/research-subjects/molecular-and-cell-biology
Funding Notes
The LISCB Studentship provides:
- 3.5 years UK tuition fees
- 3.5 years stipend at UKRI rates. For 2026/7 this will be £21,805 per year
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