The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

EDUCATION

Research Projects

Project: Turning a conserved system bad; Understanding how alterations within O-linked glycosylation biosynthesis results in toxicity in Burkholderia cenocepacia

Scott group

Burkholderia species are associated with several life-threatening human infections that often result in high morbidity and mortality rates due to their innate resistance to antibiotics. To improve clinical outcomes new therapies are needed which target conserved, yet unique, Burkholderia pathways. One such pathway is the Burkholderia O-linked protein glycosylation system which is required for virulence in Burkholderia cenocepacia and Burkholderia pseudomallei. This system relies on the O-Glycosylation gene Cluster (ogc), a five gene cluster sufficient and required for the generation of the glycan used for protein glycosylation, and the distally encoded oligosaccharyltransferase, pglL, responsible for the ligation of glycans to glycoproteins. Previous research from the lab has shown that the disruption of genes within the ogc cluster or pglL leads to profound impacts on bacterial physiology suggesting the perturbation of glycosylation may provide a novel way to control infections. Thus, this work aims to understand the sensitivity of the Burkholderia O-linked glycosylation system to manipulation and how glycosylation impacts the viability of B. cenocepacia. Utilising system biology approaches such as proteomic and CRISPRi as well as phenotypic assessments including growth/stress assays this work will explore if the dysregulation of protein glycosylation could be used as a next generation therapy to control Burkholderia infections.

Contact project supervisor for further
information and application enquiries

Project Supervisor

Dr Nichollas Scott

Project Co-supervisor

Dr Leila Jebeli

Project availability
PhD/MPhil
Master of Biomedical Science
Honours

Scott group

nichollas.scott@unimelb.edu.au

4 vacancies

Themes
Antimicrobial Resistance and Healthcare Associated Infections
Host Pathogens Interactions
Cross Cutting Disciplines
Discovery Research

The Scott Group focuses on the application of molecular microbiology and mass spectrometry (MS)-based methodologies to characterise microbial systems. The key focus of the lab is understanding how pathogens of the Burkholderia genus cause disease and why proteins decorated with carbohydrates influence Burkholderia pathogenesis.

Projects within the Scott lab: Two broad projects are currently on offer in the Scott lab; Project 1 involves using proteomics and CRISPRi based approaches to understand which glycoproteins are preferentially glycosylated within Burkholderia cenocepacia. Project 2 involves using proteomics to study the impact of Burkholderia cenocepacia infections on Eukaryotic cells using a combination of proteomics approaches.