Job Description

The Role

Prospective candidates will have a higher degree (to PhD level) in chemistry, in biochemistry or in biological chemistry. Evidence of an advanced level of competence in the purification and characterisation of metalloproteins is essential, including in the determine of metal affinities, DNA affinities of transcriptional regulators, protein structure determination and establishing the metalation status of recombinant metallo-proteins. Background knowledge of metals in biological systems and related bioinorganic chemistry are also both essential.

The post requires good skills in reporting research progress verbally, and in writing. It involves collaboration with an external partner at the Quadram Institute in Norwich.

The objective of this BBSRC programme is to make protein metalation in cells tractable in research and in biotechnology. The hypothesis being tested is that protein metalation inside cells can be calculated from free energy differences (deltaG), and that available deltaG can be read-out using metal-sensors. A purpose of this work has been to develop such calculations for bespoke (conditional) cells, to test the calculations, and to make such calculations accessible to non-specialists through easy-to-use metalation calculators. The first and last objectives are already complete, and the remaining year will focus on testing the calculator via the entrapment of metals (including cobalt, manganese, and iron) by the protein MncA. This will be done at different ratios of intracellular deltaG for various metals and tested against in vitro entrapment at the same metal ratios by folding MncA protein in matching metal buffers. Additionally, the repertoire of tractable metalloproteins will be extended to encompass kinetic trapping. The work has significance for bioscience and industrial biotechnology generally, and the manufacture of vitamin B12 specifically.

This post is fixed term for up to 12 months from 01 October 2023 at the earliest. The funding is available from BBSRC for this fixed period only and the project is time limited and will end on 30 September 2024.

Times Higher Education