Understanding the molecular basis of body odour formation by the human microbiome

The molecular basis of malodour, or body odour (BO), formation in humans is slowly emerging through improved understanding of the microbiology of the human underarm (axilla) and the molecules the body secretes into it. Working with Unilever (the iCASE partner) we have discovered particular axilla Staphylococci that produce thioalcohol-based BO odours & discovered the transporter responsible for precursor uptake (Minhas, G., Bawdon, D et al., submitted & patent filed) and also evidence for the action of specific CS-lyase enzymes that split the precursor to make the thioalcohol. In this project the student will work in the laboratories of Prof. Gavin Thomas in the Department of Biology and Prof. Anthony Wilkinson in the York Structural Biology Laboratory in the Department of Chemistry, to build on an initial crystal structure of the CS-lyase we have solved to understand the mechanism and specificity of this enzyme towards malodour precursors. The project will use molecular biology, biochemistry and structural biology to probe the catalytic mechanism, to understand how the enzyme appears to specifically recognise these unique human-derived substrates, and also to understand how inhibitors bind to the protein. Working with computer scientists in Unilever Bangalore together we will seek to use our improved understanding to design inhibitors to bring these core studies in enzyme structure and function closer to a biotechnological product. The student will work at the interface of the biology and chemistry so as to gain a thorough training in protein crystallography, biochemical methods for protein characterisation and enzyme assays, as well as molecular biology methods required for site-directed mutagenesis of the genes encoding the CS-lyase and aminoacylase.