Applications are invited for 4-year PhD studentship starting in October 2024 based in the Yusuf Hamied Department of Chemistry and the new AstraZeneca Discovery Centre on the Cambridge Biomedical Campus. The student will be working on a collaborative project jointly supervised by Prof Steven Lee (University of Cambridge) and Dr Praveen Sankaran (AstraZeneca) and will have opportunity to work across the two sites. The project is in the general field of single-molecule microscopic techniques and antibody biologics that has generated much excitement in both academia and industry.
Protein-protein interactions at high concentrations exhibit complex manifestations of molecular interactions, often forming heterogeneous and dynamic cross-reactions both at formulation and after injection. Identifying and quantifying these interactions with ensemble-based biophysical and bioanalytical methods is challenging due to poor sensitivity. These limitations lead to measurement challenges in assessing and predicting high- concentration formulation challenges such as aggregation, viscosity, and solubility in solution and dose delivery.
Single-molecule imaging techniques can image individual components, allowing us to 'read off' kinetic and stoichiometry information and determine population-level distributions of rare or important subspecies for unlocking diverse structural characteristics and dynamics of biologics. This project aims to develop and validate innovative and robust single-molecule microscopic techniques to accurately quantify the diverse forms of high-concentration aggregation, conformational diversity, and protein-protein interactions. It involves hydrophobicity imaging for high spatial resolution, detection, and quantifying subtle conformational changes to study evolving aggregation states in solution, single-molecule stoichiometry, dynamics, and interactions, which will help us characterise diverse protein aggregation forms. Furthermore, build modelling-machine learning tools by analysing protein assembly and association propensity of various high-concentrated formulations to accurately determine the properties, including aggregation, viscosity, solubility, and stability. This research will enable conclusions for assessing protein biologics' developability for high-concentration formulation.
Research in the Lee group is highly multidisciplinary, involving physical chemistry, optical physics, synthetic chemistry, image analysis and bespoke coding. This project offers a unique opportunity to work at the interface of physical chemistry, protein chemistry and structural biology in both academic and industry settings, and by the end of the studentship you will have gained a broad range of key experimental, computational and transferable skills that will serve as a springboard for a successful research career.
Further information about research in the Lee group can be found at: https: // www. ch.cam.ac.uk/group/lee/index
Applicants should have or shortly expect to obtain a first or upper second- class degree from a UK university, or an equivalent standard from an overseas university, in a relevant subject such as physics, chemistry, natural sciences or engineering.
The studentship provides a maintenance grant of £21,500 p.a., and tuition fees at the UK/home rate. Non-UK applicants will be considered if they are able to fund the overseas fees differential, or if they are awarded a suitable scholarship. Full details of the University's entrance requirements and scholarships are specified on the following link: https: // www. postgraduate.study.cam.ac.uk/
To apply, please submit an application through the University Applicant Portal: https: // www. postgraduate.study.cam.ac.uk/courses/directory/pcchpdpch for the course "PhD in Chemistry", naming Prof. Steven Lee as potential supervisor.
For any queries about this studentship, please contact Prof. Lee by email at [email protected].
Please quote reference MA38879 on your application and in any correspondence about this vacancy.
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.Department/Location
Yusuf Hamied Department of ChemistryReference
11 October 2023Closing date
30 November 2023