The biological role and structure function analyses of O-antigen modifying enzymes in the bacterial pathogen Salmonella

Salmonella is an important bacterial pathogen, affecting both humans and livestock. One virulence strategy Salmonella uses is to modify its cell surface structures to facilitate immune evasion or directly enhance virulence. This project focuses on how and why Salmonella modifies the O-antigen part of its lipopolysaccharide (LPS). The O-antigen plays a pivotal role as a virulence factor, immunodominant antigen, and phage receptor, and may influence pathogen-host tissue interactions. Modifications are thus likely to impact many aspects of this bacterial pathogen’s biology. This project builds upon a body of work in from the supervisor’s lab and concerns one specific family of O-antigen modifying proteins with a predicted acetyltransferase function. Using a broad range of molecular biology, genetic and biochemistry approaches you will study the structure/function of these proteins and you will examine the role of the modification in a set of biological assays.

The project will further our understanding of this family of little studied proteins and the process of O-antigen modification, contribute to our understanding of Salmonella as a pathogen and inform the development of LPS based vaccine approaches.

Techniques you will use include but are not limited to mutagenesis, cloning, protein expression and purification, electrophoresis, and use of software for sequence analysis/protein structure. Lab meetings, seminar series, minisymposia and the opportunity to participate in and develop outreach activities will help you develop a broad range of scientific and transferable skills. There is a vibrant PhD community that hosts events like Coffee and careers. You will be co-supervised and will carry the work out in labs specializing in protein biochemistry as well as molecular microbiology, housed in the Centre of Immunology and Infection, Department of Biology and YSBL. This project is suitable for applicants with a strong background and interest in microbiology, biochemistry and/or molecular biology, and an overall interest in the molecular basis of bacterial pathogenesis.