Applications are invited for a postdoctoral researcher position to study antibody design and molecular
mechanisms of modulation of ion channels. You will be part of the Modular Activator and Silencer Therapeutics (MAST) team developing novel platforms of antibodies, E3 ligase-mediated degraders, and proteases, to advance drug discovery, with the opportunity
for superb mentorship support from the programme, which involves the labs of Laura Itzhaki (degraders; PMID 33623657), Paul Miller (ion channel antibodies; PMID 35140402), Florian Holfelder (proteases; PMID 36765057), Mark Howarth (antibodies; PMID 36865256),
Catherine Wilson (degraders; PMID 32286286), and Pietro Sormanni (antibody design; PMID 37024501)

The applicant will develop synthetic libraries of conformational antibodies that can act as modulators of ion channels, identify
hits from phage display, and demonstrate proof-of-concept modulation by solving cryo-EM structures (and by electrophysiology). This project provides opportunities for creative protein engineering, including database mining (to build structural antibody libraries),
machine learning (AI) approaches to antibody design, phage display, and cryo-EM of ion channels.

The applicant will have completed a PhD (or soon to be awarded one), and will have relevant wet-lab experience that includes protein
engineering and/or structural biology (cryo-EM or X-ray crystallography) and/or phage display and/or computational approaches to analysing protein and antibody structure.

Recent relevant publications are:

Kasaragod VB, Mortensen M, Hardwick SW, Wahid AA, Dorovykh V, Chirgadze DY, Smart TG,
Miller PS.

Mechanisms of inhibition and activation of extrasynaptic alpha-beta GABAA receptors.
Nature, 2022, Feb, 602(7897), p. 529-533. PMID: 35140402. https://www.nature.com/articles/s41586-022-04402-z

Kasaragod VB, Malinauskas T, Wahid AA, Lengyel J, Knoflach F, Hardwick SW, Jones CF, Chen W-N, Lucas X, Omari K, Chirgadze DY, Aricescu AR, Cecere G,
Hernandez M-C, Miller PS.

The molecular basis of drug selectivity for
a5 subunit-containing GABAA receptors.
Nature Structure and Molecular Biology, 2023, Dec, 30(12), p.1936-1946. PMID: 37903907.

https://www.nature.com/articles/s41594-023-01133-1

Ramon, Aubin, Montader Ali, Misha Atkinson, Alessio Saturnino, Kieran Didi, Cristina Visentin, Stefano Ricagno, Xing Xu, Matthew
Greenig, and Pietro Sormanni.

Assessing Antibody and Nanobody Nativeness for Hit Selection and Humanization with AbNatiV.

Nature Machine Intelligence, 15 January 2024.

https://doi.org/10.1038/s42256-023-00778-3

Application Closing date: 24^th March 2024

Project start date: 14^th May 2024 with flexibility in the precise start date and continue for 24 months in the
first instance.

For more details and to apply:

https://www.jobs.cam.ac.uk/job/45358/

Informal enquiries about the position can be made to Dr Paul Miller (pm676@cam.ac.uk)

Back to the vacancy list