Decoding Vaccine Evasion in Neisseria gonorrhoeae

About the Project

The Project: Addressing a Global Health Emergency

Global cases of gonorrhoea are rising sharply, complicated by a crisis of multidrug resistance (MDR) within the causative organism, Neisseria gonorrhoeae. While the recent introduction of vaccines offers a new frontier in prevention, initial reports suggest a troubling lack of efficacy within high-risk populations.

N. gonorrhoeae is a master of genomic fluidity. It utilizes a sophisticated genetic mechanism known as phase variation—a "molecular switch" that toggles the expression of surface genes "ON" or "OFF"—to rapidly alter its immunological profile. Many of the proteins targeted by current vaccines are subject to this variation and have been linked to altered infection susceptibility in both males and females providing a potential mechanism for vaccine failure.

This project will investigate how phase-variable immunogens influence infection susceptibility and determine if this mechanism is the primary driver of vaccine failure. Your findings will directly contribute to the design of more robust, "escape-proof" vaccines for this critical STI therefore helping global efforts in reducing the reliance on antibiotics. The student will join a vibrant microbiology group in Sheffield and receive a broad training in molecular biology and microbiology as well as imaging, proteomics and bioinformatics.

Technical Training & Methodology:

The successful candidate will receive comprehensive training in a multidisciplinary suite of "bench-to-bioinformatics" techniques. You will master:

Genomic Analysis: Utilizing PCR and Sanger sequencing to track genetic shifts, alongside high-resolution DNA fragment analysis (GeneScan) to quantify phase-variable repeat tracts.

• Proteomics & Protein Expression: Characterizing the surface "phenotype" of the bacteria using Western blotting and state-of-theart LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry) to identify and quantify immunogen expression.
• Microbial Phenotyping: Assessing how these molecular changes alter bacterial fitness and host-cell interactions through novel designed 3D tissue models.

Research Environment: The University of Sheffield

As a prestigious member of the Russell Group, The University of Sheffield is ranked in the top 100 universities globally. This project is based within the School of Clinical Dentistry (SCD), a premier centre for oral and systemic health research with recent REF results demonstrating our research as ‘world-leading’ or ‘internationally excellent’. The School hosts a world-class Integrated BioScience research group with a heavy focus on fundamental microbiology and host-pathogen interactions.

• State-of-the-Art Facilities: You will have access to dedicated Class II microbiology labs and the University’s core facilities for advanced proteomics and genomics.
• Multidisciplinary Synergy: Work alongside experts in microbial pathogenesis and immunology, benefiting from a collaborative "bench-to-bedside" atmosphere.
• Professional Development: Enrolment in the Think Ahead program provides bespoke training in leadership, public engagement, and data analysis.

Entry Requirements

Academically excellent (MSc, BSc 2:1 or above) students in a relevant subject, alongside an enthusiasm for microbial genetics should informally contact Dr Luke Green. We welcome enquiries from self and government funded overseas students as we are proud that the group is a multinational team.

How to Apply

Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgraduate/phd/ apply/applying.

Please clearly state the prospective main supervisor in the respective box and select ‘School of Clinical Dentistry’ as the department.

Enquiries: For further information contact Dr Luke Green for details (l.r.green@sheffield.ac.uk).

Funding Notes

This opportunity is for self-funded applicants who are able to fund this themselves, or obtain funding from another source (Government sponsored etc). This project is for 4 years, so will require 4 years of fees and will require an additional £12,000 per year to run the project. This is open to both home and overseas applicants.

Proposed start date - 1st October 2026