About the project
This project aims to uncover the structural dynamics of membrane proteins involved in antimicrobial resistance (AMR) of bacteria. AMR is recognised by the United Nations as a global health emergency.
The project's focus is on multidrug efflux systems. These play major roles in AMR, specifically the resistance-nodulation-division (RND) protein class.
Membrane protein efflux pumps can expel a broad range of toxic substances out of bacteria. These significantly contribute to multidrug resistance against functionally diverse antimicrobial drugs and biofilm formation. Biofilms typically pose a great issue for implants as they provide an ideal solid support to promote growth. Treatment of such infections is extremely difficult, normally resulting in the removal of the implant.
We plan to expand our research in 2 ways:
- the exploration of related efflux proteins and systems, away from the prototypical, to broaden our understanding of the fundamental role structural dynamics plays in multidrug resistance phenotypes
- adapt our methods to interface with biofilm systems, to understand the role these efflux systems play in bacterial infection and resistance
You will use and develop microbiology, chemical biology, and advanced mass spectrometry strategies to enable membrane protein dynamics to be deciphered within complex environments. These dynamics will be captured with Hydrogen/Deuterium exchange Mass Spectrometry (HDX-MS). This measures the extent and rate of exchange of protein backbone amide hydrogens for deuterium. Combining these insights with biofilm systems and assays will provide unprecedented insight into the function of these systems, particularly on the impact of drug interactions and clinically relevant mutations.
This is an interdisciplinary project and you will receive training in a range of the following microbiology and chemical biology techniques:
- mass spectrometry
- biophysical and biochemical techniques
- molecular biology and cloning
- biofilm microbiology
You will be working at the interface of microbiology and chemical biology and have the option to attend relevant international conferences and training events.
