Postdoctoral Fellow
Research Fellow in Protein Chemistry / Biological Mass Spectrometry Full-time
Are you an ambitious researcher looking for your next challenge? Do you have an established background in Protein Chemistry, Structural Mass Spectrometry or Biophysics? Do you want to further your career in one of the UKs leading research intensive Universities?
Biomolecular condensates are multicomponent structures comprised of specific repertoires of proteins/RNA, and are formed via liquid-liquid phase separation (LLPS). They play key roles in organising cells, signalling, stress and viral factory formation, whilst aberrant LLPS is associated with several neurodegenerative diseases (e.g. motor neurone disease and dementia). Biomolecular condensates are heterogeneous and dynamic, making it challenging to elucidate their composition, structure and biogenesis. We are looking for a postdoctoral research fellow to join a team of researchers investigating the mechanisms by which biomolecular condensates form using a combination of structural mass spectrometry (including native mass spectrometry, covalent footprinting, chemical crosslinking and hydrogen-deuterium exchange), proteomics, biochemistry, biophysics and cell biology. Overall, we aim to develop and deploy a toolkit of methods to interrogate the formation of biomolecular condensates both in vitro and in cell.
This project focuses on studying the conformational dynamics, protein-protein and protein-nucleic acid interactions that underlie LLPS and aberrant phase transitions and has two key foci. First, we aim to reveal the molecular grammar underlying the formation of viral replication factories, using Rotaviruses as a model system, in order to identify key weaknesses in the viral factory assembly pathway that could be targeted by new antiviral therapies [this builds on our previous work (Bravo et al., Nucleic Acids Research, 46, 2018, 7924–7937; Bravo et al., bioRxiv 2020.10.26.354233)]. Secondly, we aim to reveal the mechanism by which liquid-to-solid phase transitions occur by the protein TDP-43. Intracellular TDP-43 deposits are associated with neurodegenerative diseases including motor neurone disease and dementia, and understanding the molecular details of TDP-43 phase separation and aggregation is key to elucidating disease mechanisms and identifying therapeutic targets.
You will be based in the laboratory of Dr Antonio Calabrese (Sir Henry Dale Fellow), and will work closely with collaborators at Leeds, across the UK and internationally. You will have a PhD (or be close to completion) in Chemistry, Biochemistry, Biophysics or a related discipline. You will have an interest in analytical techniques, and whilst some mass spectrometry experience would be an advantage, training will be provided.