Unravelling interkingdom signalling using chemical probes

Supervisor(s)

Contact Dr Megan Wright to discuss this project further informally.

Project description

This proposal is representative of the projects currently on offer in our group. For more details of active research projects, please visit our webpage at: https://wright.leeds.ac.uk/ In this project you will synthesise and apply chemical tools to understand the mode of action of small molecules in cells. Rising antimicrobial resistance is a global threat to human health and we need new approaches to tackle bacterial infections. There are ten times as many bacterial as human cells in the human body, yet our understanding of this complex microbiome is rather poor.

Cells communicate via chemical signals and there is increasing evidence that bacterial and human cells ‘listen in’ on each other’s communications. For example, bacteria respond to human signalling molecules such as hormones, peptides, lipids and steroids. However, the mechanisms by which bacteria detect host signals are not clear: we lack information on how signals are sensed at the molecular level and how signal transduction pathways operate. In this project you will construct novel chemical tools and platforms to study such ‘interkingdom’ signalling.

In the group we are developing chemical tools to study small molecule-protein interactions in a wide variety of biological systems. We are interested in mapping ligand binding sites on receptors, profiling protein post-translational modifications, and identifying the protein targets of bioactive compounds. One of our approaches is to synthesise functional probes that are ‘weaponised’ with reactive tags to covalently label proteins, and that are also equipped with additional tags to capture probe-protein complexes for further analysis.

This capture chemistry is very versatile and can be used to attach different chemical groups for imaging or identification of proteins by mass spectrometry. In this project you will synthesise new functional probes and apply them to unravel the mode of action of human signals in bacterial pathogens. Over the course of the project you will receive training in organic synthesis, cell biology, biochemical techniques and mass spectrometry-based proteomics. This project would ideally suit a candidate with a chemistry background and a strong interest in applying chemistry to biological problems. 

Entry requirements

Applications are invited from candidates with or expecting a minimum of a UK upper second class honours degree (2:1), and/or a Master's degree in a relevant science subject such as (but not limited to) chemistry or biochemistry.

If English is not your first language, you must provide evidence that you meet the University’s minimum English Language requirements.

How to apply

Formal applications for research degree study should be made online through the university's website. Please state clearly in the research information section that the PhD you wish to be considered for is 'Unravelling interkingdom signalling using chemical probes' as well as Dr Megan Wright as your proposed supervisor.

We welcome scholarship applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.

If you require any further information please contact the Graduate School Office e: maps.pgr.admissions@leeds.ac.uk