We are interested in both fundamental studies of membrane proteins and in how this particular class of proteins might be used in synthetic biology. Current projects are:

Designing de novo membrane proteins. We are using computational and rational methods to design artificial membrane proteins. In doing so, we aim to explore the fundamental principles that control the folding, assembly and function of this class of protein. How important and 'special' are the specific amino acid sequences and structures of natural membrane proteins - could alternative folds do the same job? Does the sequence richness and complexity of natural proteins matter, or would simpler minimal sequences suffice? What are the rules that govern the assembly of membrane proteins into their final, functional form? And do we  know enough about membrane proteins to build them ourselves? 

Our particular focus is on designing membrane proteins that can bind heme. We have identified sequences that can effectively bind heme in vitro, and are now developing these designs so that they can be fully integrated into living cells. In the long-term such artificial proteins could be used as novel enzymes, localise biochemical processes to membrane sites, or substitute into electron transfer pathways for 'synthetic bioenergetics'.

References

Curnow P, Hardy BJ, Dufour V, Arthur CJ, Stenner R, Hodgson LR, Verkade P, Williams C, Shoemark DK, Sessions RB, Crump MP, Jones MR and Anderson JLR (2020) Small-residue packing motifs modulate the structure and function of a minimal de novo membrane protein. Scientific Reports 10 15203

Curnow P. (2019) Designing minimalist membrane proteins. Biochem Soc Trans 47 (5): 1233-1245.

Lalaurie CJ, Dufour V, Meletiou A, Ratcliffe S, Harland A, Wilson O, Vamasiri C, Shoemark DK, Williams C, Arthur CJ, Sessions RB, Crump MP, Anderson JLRA and Curnow P (2018) Design of a biocompatible and catalytic de novomembrane protein. Scientific Reports 8 14564

Biomineralization. Inorganic minerals are widespread and diverse in nature, being important constituents of structures including bone, tooth and shell. However, the underlying biological mechanisms behind biomineral synthesis remain only partly understood. We are interested in the roles played by membrane transport proteins and other biomolecules in biomineralization. This is pursued through collaborations with colleagues in the Schools of Chemistry and Earth Sciences here at Bristol.

Yeast acyltransferases. Brewer’s yeast contains a number of membrane-associated enzymes (acyltransferases) that make biochemicals which control the flavour of fermented beverages such as wine and beer. We have developed novel methods to understand the structure and function of these enzymes and are now curious as to whether they could be used as environmentally-friendly cellular factories for the production of fragrances and fine chemicals.

Antibiotic discovery. A new collaboration with Prof. Paul Race seeks to discover novel antibiotics (and other natural products) from deep-sea bacteria. This project is made possible through a unique collection of deep-sea sponges obtained by colleagues in Earth Sciences at Bristol. This was prompted by the emergence of antimicrobial resistance (AMR) as a major threat to global health.