Department of Pharmacology & Astra-Zeneca funded PhD studentship: Development of novel formats of antibodies and toxins against cell surface receptors to benefit pharmacology
Supervisors: Paul Miller (Pharmacology) / Steven Rust (AstraZeneca)
The Miller lab is engaged in the study of protein binders and modulators, such as antibodies and toxins, of cell surface receptors, especially ion channels (1-3). These can have important uses as novel pharmacological tools to aid fundamental and disease research, and as future therapeutics. In certain instances the nature of the binder or the receptor target means that the potency of binding and modulation is sub-optimal. Furthermore, the receptor target localisation, for example if expressed in the central nervous system or in a tumor, can prohibit access by the binder. This project will focus on protein engineering of antibodies and toxins to enrich them at the cell surface in order to increase potency and alter the in vivo biodistribution properties. It is anticipated that this work will improve understanding of these engineering approaches and provide generic strategies to enhance the action of protein binders and modulators against cell surface receptors such as ion channels, with obvious beneficial consequences for research and therapeutic development.
Techniques will include molecular biology, protein engineering, cell binding and functional pharmacology assays, in vivo biodistribution studies, and cell/tissue imaging (and possibly electrophysiology).
This studentship will primarily be located in the Miller lab, Department of Pharmacology, but will also involve undertaking a placement at Astra Zeneca, Cambridge.
Funding covers the tuition fees at the UK rate, and includes a generous student stipend for 3.5 years.
Should you wish to know more about this project before formally applying then contact, Dr Paul Miller (firstname.lastname@example.org), including your CV.
1) Vikram B. Kasaragod, Martin Mortensen, Steven W. Hardwick, Ayla A. Wahid, Valentina Dorovykh, Dimitri Y. Chirgadze, Trevor G. Smart, Paul S. Miller. Mechanisms of inhibition and activation of extrasynaptic ¿¿ GABAA receptors. Nature (COMING SOON!)2) Miller. PS et al (25 authors). Heteromeric GABAA receptor structures in positively-modulated active states. BioRxiv https://www.biorxiv.org/content/early/2018/06/05/338343.3) Miller. PS, Scott. S, Masiulis. S, De Colibus. L, Pardon. E, Steyaert. J, Aricescu. AR. Structural basis for GABAA receptor potentiation by neurosteroids. Nature Structure and Molecular Biology. 2017, 24(11), p. 986-992.
Fixed-term: The funds for this post are available for 3.5 years in the first instance.
Key words: antibodies, toxins, protein engineering, biodistribution
APPLICATION PROCEDUREApply formally to the University using the online application form (Applicant Portal). For more information, see https://www.phar.cam.ac.uk/postgraduate-admissionsProject related questions may be addressed directly to the supervisor (see above). Requests for general information or enquiries about procedures including advice if you have already submitted an application to our Department via email to email@example.com
Online applications with ALL supporting documentation to be submitted by12 midday on Monday 24th January 2022 at the latest.
Interview dates to be confirmed.
Please quote reference PL29434 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.
The University has a responsibility to ensure that all employees are eligible to live and work in the UK.