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

通过对人类腋下（腋窝）的微生物学和身体分泌到腋下的分子的更好理解，人类恶臭或体臭（BO）形成的分子基础正在慢慢出现。与联合利华（iCASE合作伙伴）合作，我们发现了产生基于硫醇的BO气味的特定腋窝葡萄球菌，并发现了负责前体摄取的转运蛋白（Minhas，G.，Bawdon，D等人，提交和专利申请），也有证据表明，特定的CS-裂解酶的作用，分裂的前体，使硫醇。在这个项目中，学生将在生物系Gavin托马斯教授和化学系约克结构生物学实验室的Anthony威尔金森教授的实验室工作，以我们已经解决的CS-裂解酶的初始晶体结构为基础，了解这种酶对恶臭前体的机制和特异性。该项目将使用分子生物学，生物化学和结构生物学来探索催化机制，了解酶如何特异性识别这些独特的人类来源的底物，并了解抑制剂如何与蛋白质结合。与联合利华班加罗尔的计算机科学家合作，我们将寻求利用我们更好的理解来设计抑制剂，使这些酶结构和功能的核心研究更接近生物技术产品。学生将在生物学和化学的界面工作，以便获得蛋白质晶体学，蛋白质表征和酶测定的生物化学方法以及编码CS-裂解酶和氨基酰化酶的基因的定点诱变所需的分子生物学方法的全面培训。

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.