Research Associate in de novo metalloenzyme design

The role

A post-doctoral position is available to develop new metalloprotein scaffolds and elaborate these into de novo enzymes. This post is available for 12 months in the first instance. It is in the protein design laboratory of Prof Dek Woolfson (Chemistry and Biochemistry, University of Bristol). The appointed post-doc would design de novo metalloenzymes based on new alpha-helical barrel proteins using computational design, and protein biochemistry.

What will you be doing?

Specifically, the work will develop de novo alpha-helical barrel proteins recently designed by the Woolfson group (Nature Chemical Biology 20,991-999 (2024)), based on its foregoing peptide assemblies (Science346, 485-8 (2014)). Unlike most natural peptide assemblies and proteins, these alpha-helical barrel peptides and proteins have solvent-accessible channels running completely through them. These lumens have dimensions accessible to small molecules, and the Woolfson group has shown that they can be modified through rational or computational design to incorporate new functions. Specifically, catalytic activity can be installed into the alpha-helical barrel peptides (Nature Chemistry 8, 837-44 (2016)). The new single-chain alpha-helical barrel proteins open possibilities to extend this work considerably towards the construction of de novo enzymes. The aim of this project is to design alpha-helical barrel proteins that bind metal and metal clusters capable of facilitating catalytic reactions.

You should apply if

The position would be suited to a talented and ambitious early career researcher with an interest in applying de novo protein design in biocatalysis and chemical or synthetic biology. Essential skills for the role include experience with the design or engineering and production of natural or de novo proteins; and the biophysical and structural characterisation of proteins, including crystallography. Experience in enzymology would be an advantage.