Understanding the role of lipid A modification and outer membrane vesicles during Porphyromonas gingivalis biofilm formation
Project details
First supervisor: Dr James Garnett
Second supervisor: Professor Mike Curtis
Funding available: Self-funded.
Duration of award: 4 years full-time.
Start date: Open until suitable candidate is found.
Application deadline: Open until suitable candidate is found.
Reference number: 2024/DOCS/JG
Project description
Biofilms are the predominant mode of growth for countless microorganisms, which adhere to one another and are encased within a self-produced extracellular mesh of carbohydrate, protein, lipid, and nucleic acid.Porphyromonas gingivalis is a Gram-negative pathogenic bacterium contained within multispecies biofilms in the oral cavity and is a causative agent of chronic periodontitis. Unlike dominant pathogens (e.g., Clostridium difficile) that manipulate their environment to outgrow indigenous microbiota, P. gingivalis is a low-abundance microbe that can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. It uses a type-9 secretion system (T9SS/PorSS) to export virulence factors (e.g., gingipains: RgpA, RgpB, Kgp) across its outer membrane which are then covalently attached to the bacterial surface via a specific type of liposaccharide (anionic-lipopolysaccharide; A-LPS). These are also subsequently sorted into outer membrane vesicles (OMVs); however, this process is not well understood, nor is the precise activity of the T9SS and OMVs during P. gingivalis biofilm growth.
The overall aim of this PhD project is to understand how changes in lipid A structure, linked to T9SS regulation and OMV formation, affect P. gingivalis biofilm formation. 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
Candidates will develop and enhance their skills in:
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Microbiology
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Biofilm studies (including microfluidics)
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Confocal microscopy
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Eukaryotic cellular infection models
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Proteomics
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Metagenomics
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Biochemistry/biophysicsStructural Biology
To view entry requirements and further general information, see Dental and Health Sciences Research MPhil/PhD prospectus page.
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:
- Register a new account/login.
- Once logged in, select Create a new application.
- Enter ‘Dental and Health Sciences Research MPhil/PhD (Full-time)/(Part-time)' under Choose a programme. Please ensure you select the correct mode of study.
- Select a start date from the list.
- Please note: Applicants must include the project reference number (2024/DOCS/JG) in the 'Research proposal' and 'Funding (point 5)' sections of the application.
Name: Dr James Garnett
Email: james.garnett@kcl.ac.uk
Related Centre: Centre for Host-Microbiome Interactions
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