Structural studies of type II secretion in Legionella pneumophila

First supervisor: Dr James Garnett

Funding available: Self-funded PhD students only

Duration of award: 4 years

Mode of study: Full-time

Eligibility: Home, EU & Overseas

Start date:  Open until a suitable candidate is found

Application deadline:  Open until a suitable candidate is found

Reference number:  2024/10/JG/DOCS

Project description

Many Gram-negative bacteria use a type II secretion system (T2SS) to export proteins to the bacterial surface and/or the extracellular milieu. In Legionella pneumophila this system transports as many as 254 substrates/effectors out of the bacterium, which represents the largest known catalogue of substrates secreted by a T2SS. These substrates exhibit a wide range of functions that include biofilm formation, nutrient acquisition, dampening of host innate immunity and initiating the early stages of infection. The T2SS spans both the inner and outer membranes, and in L. pneumophila 12 genes have been identified across 5 loci: lspC, lspDE, lspFGHIJK, lspLM and lspO. LspD forms a pentadecameric outer membrane pore (the secretin) and bridges the inner membrane through interactions with an assembly platform (LspC, LspF, LspL, LspM). We have identified how some substrates are recognised in the periplasm, and this results in recruitment of an ATPase (LspE), formation of a pseudo-pilus, and active transport of the substrate through the secretin pore.

The overall aim of this PhD project is to understand how the recognition of substrates initiates conformational change in the T2SS. This will be tackled using structural biology techniques (primarily cryo-EM and NMR) coupled with biochemical and cellular assays. Gaining molecular insights here will allow us to understand new biological processes but may also present novel drug targets for developing new antibacterial compounds.

Person specification

We will consider applications from prospective students with a good biomedical/biochemical, microbiology or similar degree (minimum of a 2:1). 

Research training

• Structural Biology (cryo-EM, NMR, X-ray crystallography, SAXS)
• Biochemistry/biophysics
• Protein purification
• Protein:protein/ligand interactions
• Microbiology
• Biofilm studies (including microfluidics)
• Confocal microscopy

To view entry requirements and further information, see the Dental and Health Sciences Research MPhil/PhD. 

Next steps

Applicants are strongly encouraged to discuss projects with the first supervisor prior to submitting an application. 

Please apply online at apply.kcl.ac.uk following these steps:

1. Register a new account/login.
2. Once logged in, select Create a new application.
3. Enter ‘Dental and Health Sciences Research MPhil/PhD (Full-time)' under Choose a programme. Please ensure you select the correct mode of study.
4. Select a start date from the list.
5. Please note: Applicants must include the project reference number (2024/10/JG/DOCS) in the 'Research proposal' and 'Funding (point 5)' sections of the application.

Contact for further information

Dr James Garnett

james.garnett@kcl.ac.uk

Related Centre Centre for Host-Microbiome Interactions

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