Profiling the mycobacterial biofilm; a multidisciplinary mix of mutants and mass spectrometry

The aim of this project is to advance and develop secondary ion mass spectrometry (SIMS) imaging capabilities for biofilm imaging and antimicrobial metabolic pathways identification.

It is estimated that by 2050 there will be over 10 million extra deaths due to antimicrobial resistance (AMR) (O’Neill report 2014) and we urgently need novel multi-disciplinary approaches to combat this global health threat. The link between AMR and biofilms is unequivocal and mycobacterial biofilms are likely to be responsible for increased treatment failure in diseases such as tuberculosis and cystic fibrosis, yet we do not yet fully understand why.

With the potential of high-throughput, high-resolution and high-sensitivity label-free imaging in 3D, secondary ion mass spectrometry imaging methods are, arguably, ones of the most powerful techniques for high-resolution chemical imaging of biological samples. However, there are some critical limitations for the analyses of complex bacterial systems, which need careful consideration and require methodology development. The objectives of this project are to develop and optimise methods needed for 3D imaging of antibiotics in bacteria and biofilms using SIMS, including a unique 3D OrbiSIMS with cryo-SIMS capability and NanoSIMS instruments at NPL.

The developed measurement capabilities will be used to address the key question of whether increased AMR in mycobacterial biofilms is due to reduced antibiotic penetration or due to phenotypic changes in the bacteria themselves.

The use of NPLs world-class facilities in conjunction with the microbiology facilities and expertise in bacterial mutagenesis at the University of Surrey will address the urgent need for new understanding of antimicrobial resistance of mycobacterial biofilms and provide the opportunity for high-impact publications and excellent doctoral training.

The project will be undertaken in collaboration with the National Physical Laboratory, the UK’s national metrology institute, where 3D OrbiSIMS and NanoSIMS instruments are successfully used for high resolution imaging of biological samples and the University of Surrey’s Faculty of Health and Medical Sciences.

This position will be 0.5 FTE at NPL and 0.5 FTE at the University of Surrey

This is a full time PhD project, which is planned for a period of three years from October 2018.  Students are initially registered for a PhD with probationary status and, subject to satisfactory progress, subsequently confirmed as having PhD status.

Applicants should have a first or upper second class UK honours degree or equivalent in a related discipline, such as mechanical engineering or physics. An appreciation of precision engineering and experience in microbiology would be advantageous.