Dr Yin Chen, Prof D J Scanlan
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
About the Project
This project is available through the MIBTP programme on a competition basis. The successful applicant will join the MIBTP cohort and will take part in all of the training offered by the programme. For further details please visit the MIBTP website - https://warwick.ac.uk/fac/cross_fac/mibtp/
Antimicrobial resistance (AMR) is one of the most serious threats to humans in the 21st century. A promising approach for combating AMR is phage therapy. Bacteriophages are viruses that exclusively attack and lyse a bacterium, including bacterial pathogens. However, like all clinical procedures, phage therapy is subject to failure and the mechanisms underpinning unsuccessful phage therapy are not well established.
We hypothesize that the cell surface of bacterial pathogens plays a vital role in determining the success or failure of phage therapy in combating AMR. This project therefore aims to determine whether there is another, previously overlooked, dimension to combat antimicrobial resistance, namely the remodelling of membrane lipids. Lipid renovation is a process whereby bacteria selectively modify their membrane composition in response to a particular environmental stimulus, e.g. the availability of a specific nutrient. Such remodelling potentially plays a role in dictating the relative abundance of cell surface molecules such as membrane proteins, lipopolysaccharides both of which are known phage receptors.
We have previously isolated many bacteriophages targeting specific bacterial pathogens. Using cutting-edge lipidomics, transcriptomics and proteomics approaches, this project aims to provide a mechanistic understanding of the role of the cell surface in combating antimicrobial resistance and pathogenesis.
BBSRC Strategic Research Priority: Understanding the rules of life: Systems Biology
Techniques that will be undertaken during the project:
• Cutting edge ‘omics tool sets and associated bioinformatics, including lipidomics, transcriptomics and proteomics
• Molecular genetics and targeted mutagenesis
• Analytical skills including HPLC, ion-exchange chromatography and gas chromatography
• Biochemical skills, including membrane protein isolation and purification and mass spectrometry
• Health and safety training and handling of class-2 human pathogens
References
Blair JM, et al 2015 Molecular mechanisms of antimicrobial resistance. Nature Reviews Microbiology 13:42-51.
Salmond & Fineran 2015. A century of the phage: past present and future. Nature Reviews Microbiology 13:777-785.
Nikaido H 2003 Molecular basis of bacterial outer membrane permeability revisited. Microbiology and Molecular biology Reviews 67(4)593-656.