MRes Infectious & Tropical Diseases - Pathogen Biology (viruses & bacteria)

ID	Title	Overview
PB1	Tools for differentiating Chikungunya (CHIKV), Ndumu (NDUV), and O'nyong-nyong (ONNV) viruses (UKHSA, Porton Down, UK)	Emerging alphaviruses such as Chikungunya virus, O’nyong-nyong virus and Ndumu virus circulate in overlapping regions but remain difficult to differentiate using routine diagnostics due to genetic and serological similarity. You will develop non-infectious diagnostic tools that enable safe detection and discrimination of these viruses without the need for virus culture. Question: can molecular and serological platforms reliably distinguish closely related alphaviruses while minimising biosafety risks? To address this you will (1) design & evaluate nucleic acid assays capable of discriminating CHIKV, ONNV & NDUV using synthetic RNA standards; (2) develop non-infectious serological assays using pseudotyped reporter systems to assess antibody cross-reactivity; and (3) integrate data into a diagnostic decision framework for safe alphavirus detection and surveillance.
PB2	Dissecting the role of the T6SS to antagonize the gut microbiome by enteric pathogens (London)	Our previous work has shown that the Type VI Secretion System (T6SS) of Klebsiella pneumoniae acts as a contractile nanoweapon that promotes gut colonization by delivering antibacterial and antifungal toxins in a contact-dependent manner. This project will define how Klebsiella assembles and regulates T6SS architecture using fluorescently tagged components and single-cell confocal live imaging to quantify sheath dynamics and length control. You will determine how T6SS deployment changes in response to representative mouse and human gut microbiota species. You will generate targeted single and combinatorial mutants using a high-throughput CRISPR–Cas9 platform and carry out quantitative in vitro killing assays under gut-relevant conditions. This work will provide a structure-function framework for understanding how T6SS shapes microbiome composition.
PB3	Beyond the model strain: decoding Campylobacter genome function through C. coli (London)	Understanding how bacterial gene interactions drive virulence and antimicrobial resistance (AMR) remains a major challenge. The convergence of genomics and artificial intelligence (AI) enables a shift toward analysing contemporary, globally important strains. Campylobacter is an ideal model due to its compact genome and global burden. C. coli, a significant cause of human disease, remains understudied despite higher AMR rates than C. jejuni. You will analyse clinically relevant isolates using quantitative phenotyping (cell culture, infection models, AMR profiling) and host models (Galleria, Acanthamoeba, zebrafish). Integration of multidimensional phenotypic and whole-genome data with AI will reveal mechanisms of adaptation, virulence and AMR. This systems-level approach moves beyond single-gene analyses toward translational impact in surveillance, risk stratification and intervention development.
PB4	Dissecting the antibacterial role of Campylobacter's T6SS and its effectors (London)	Campylobacter jejuni is a leading bacterial agent responsible for infectious diarrhoea worldwide, presenting a significant global health challenge. Despite its prevalence, the molecular and cellular mechanisms underlying human enteric disease caused by C. jejuni remain fragmented and poorly understood. Recently, we uncovered the presence of Type VI Secretion System (T6SS) in several C. jejuni lineages. However, the contribution of C. jejuni T6SS to infection outcomes remains unknown. You will explore the hypothesis that the T6SS and its associated effectors play key roles in orchestrating C. jejuni niche establishment through antibacterial competition within diverse host environments. We anticipate uncovering fundamental processes through which the T6SS and its effectors equips C. jejuni with antibacterial properties to thrive in specific host environments.
PB5	Investigating menaquinone-mediated resensitisation of drug-resistant tuberculosis (London)	Drug-resistant tuberculosis remains a major global health challenge and threatens the effectiveness of existing therapies. We recently demonstrated that inhibition of menaquinone biosynthesis can resensitise Mycobacterium tuberculosis strains that have acquired resistance to bedaquiline, a cornerstone of drug-resistant tuberculosis treatment, by disrupting bacterial respiration and energy metabolism. You will investigate menaquinone-mediated resensitisation as a strategy to enhance the activity of treatment regimens. Using in vitro models, you will assess whether inhibition of menaquinone biosynthesis enhances other clinical drugs. Experiments will also examine how these interactions change under conditions designed to mimic host-relevant environments, including altered carbon sources, acidic pH and hypoxia. Together, the work will define the potential of targeting bacterial respiration to restore antibiotic activity and inform future therapeutic strategies.
PB6	Vitamin B12–dependent remodeling of the Mycobacterial surfaceome (London)	TB causes over 1 million deaths annually, reflecting gaps in Mtb biology. We study how nutrient acquisition and sensing shape mycobacterial metabolism, focusing on cobalamin (B12) regulation and transport. Hypothesis: Exogenous B12 activates a surface program that enables envelope traversal and couples to inner membrane uptake. Aims: Using Mycobacterium smegmatis as a model, the MRes will: (1) Map the surfaceome under defined B12 conditions. (2) Quantify inner/outer membrane transport modules. (3) Test causality using a phenotype defined panel. We plan to pair a B12 dependent methionine background lacking de novo B12 with surface focused proteomics. You will build: B12 prototroph; B12 biosynthesis auxotroph; tunable B12 dependent background; variants with single/multiple transporter capacity losses; and apply live cell shaving, membrane proteomics (PRM/SRM), and labeled B12 uptake assays to define envelope phenotypes.
PB7	Characterising mycobacterial genomic diversity using sequencing, bioinformatics, and AI (London)	Mycobacterium tuberculosis complex bacteria (Mtb), the cause of TB, and nontuberculous mycobacteria (NTM) are public health concerns, responsible for global burdens of (extra)pulmonary infection. Drug resistance (DR) further complicates treatment and control. Whole-genome sequencing (WGS) of Mtb can identify mutations associated with resistance to 17 anti-TB drugs, define sub-lineages linked to virulence, and support phylogenetic analyses of transmission. In contrast, the biology, DR mechanisms, and transmission dynamics of NTM are poorly understood. You will use WGS, including Oxford Nanopore long-read sequencing, to characterise the genomic diversity of Mtb and NTM species, including M. avium and M. abscessus complexes. Integrating genomic data across species, you will identify genetic determinants of DR, develop AI models for genotypic DR prediction, and investigate transmission using strain-relatedness to support improved diagnostics, surveillance, and clinical management.

Title

Overview

PB1

Tools for differentiating Chikungunya (CHIKV), Ndumu (NDUV), and O'nyong-nyong (ONNV) viruses

(UKHSA, Porton Down, UK)

Emerging alphaviruses such as Chikungunya virus, O’nyong-nyong virus and Ndumu virus circulate in overlapping regions but remain difficult to differentiate using routine diagnostics due to genetic and serological similarity. You will develop non-infectious diagnostic tools that enable safe detection and discrimination of these viruses without the need for virus culture.

Question: can molecular and serological platforms reliably distinguish closely related alphaviruses while minimising biosafety risks?

To address this you will (1) design & evaluate nucleic acid assays capable of discriminating CHIKV, ONNV & NDUV using synthetic RNA standards; (2) develop non-infectious serological assays using pseudotyped reporter systems to assess antibody cross-reactivity; and (3) integrate data into a diagnostic decision framework for safe alphavirus detection and surveillance.

PB2

Dissecting the role of the T6SS to antagonize the gut microbiome by enteric pathogens

(London)

Our previous work has shown that the Type VI Secretion System (T6SS) of Klebsiella pneumoniae acts as a contractile nanoweapon that promotes gut colonization by delivering antibacterial and antifungal toxins in a contact-dependent manner.

This project will define how Klebsiella assembles and regulates T6SS architecture using fluorescently tagged components and single-cell confocal live imaging to quantify sheath dynamics and length control. You will determine how T6SS deployment changes in response to representative mouse and human gut microbiota species. You will generate targeted single and combinatorial mutants using a high-throughput CRISPR–Cas9 platform and carry out quantitative in vitro killing assays under gut-relevant conditions. This work will provide a structure-function framework for understanding how T6SS shapes microbiome composition.

PB3

Beyond the model strain: decoding Campylobacter genome function through C. coli

(London)

Understanding how bacterial gene interactions drive virulence and antimicrobial resistance (AMR) remains a major challenge. The convergence of genomics and artificial intelligence (AI) enables a shift toward analysing contemporary, globally important strains. Campylobacter is an ideal model due to its compact genome and global burden. C. coli, a significant cause of human disease, remains understudied despite higher AMR rates than C. jejuni.

You will analyse clinically relevant isolates using quantitative phenotyping (cell culture, infection models, AMR profiling) and host models (Galleria, Acanthamoeba, zebrafish). Integration of multidimensional phenotypic and whole-genome data with AI will reveal mechanisms of adaptation, virulence and AMR. This systems-level approach moves beyond single-gene analyses toward translational impact in surveillance, risk stratification and intervention development.

PB4

Dissecting the antibacterial role of Campylobacter's T6SS and its effectors

(London)

Campylobacter jejuni is a leading bacterial agent responsible for infectious diarrhoea worldwide, presenting a significant global health challenge. Despite its prevalence, the molecular and cellular mechanisms underlying human enteric disease caused by C. jejuni remain fragmented and poorly understood. Recently, we uncovered the presence of Type VI Secretion System (T6SS) in several C. jejuni lineages. However, the contribution of C. jejuni T6SS to infection outcomes remains unknown.

You will explore the hypothesis that the T6SS and its associated effectors play key roles in orchestrating C. jejuni niche establishment through antibacterial competition within diverse host environments. We anticipate uncovering fundamental processes through which the T6SS and its effectors equips C. jejuni with antibacterial properties to thrive in specific host environments.

PB5

Investigating menaquinone-mediated resensitisation of drug-resistant tuberculosis

(London)

Drug-resistant tuberculosis remains a major global health challenge and threatens the effectiveness of existing therapies. We recently demonstrated that inhibition of menaquinone biosynthesis can resensitise Mycobacterium tuberculosis strains that have acquired resistance to bedaquiline, a cornerstone of drug-resistant tuberculosis treatment, by disrupting bacterial respiration and energy metabolism.

You will investigate menaquinone-mediated resensitisation as a strategy to enhance the activity of treatment regimens. Using in vitro models, you will assess whether inhibition of menaquinone biosynthesis enhances other clinical drugs. Experiments will also examine how these interactions change under conditions designed to mimic host-relevant environments, including altered carbon sources, acidic pH and hypoxia. Together, the work will define the potential of targeting bacterial respiration to restore antibiotic activity and inform future therapeutic strategies.

PB6

Vitamin B12–dependent remodeling of the Mycobacterial surfaceome

(London)

TB causes over 1 million deaths annually, reflecting gaps in Mtb biology. We study how nutrient acquisition and sensing shape mycobacterial metabolism, focusing on cobalamin (B12) regulation and transport.

Hypothesis: Exogenous B12 activates a surface program that enables envelope traversal and couples to inner membrane uptake.

Aims: Using Mycobacterium smegmatis as a model, the MRes will:

(1) Map the surfaceome under defined B12 conditions.

(2) Quantify inner/outer membrane transport modules.

(3) Test causality using a phenotype defined panel.

We plan to pair a B12 dependent methionine background lacking de novo B12 with surface focused proteomics. You will build: B12 prototroph; B12 biosynthesis auxotroph; tunable B12 dependent background; variants with single/multiple transporter capacity losses; and apply live cell shaving, membrane proteomics (PRM/SRM), and labeled B12 uptake assays to define envelope phenotypes.

PB7

Characterising mycobacterial genomic diversity using sequencing, bioinformatics, and AI

(London)

Mycobacterium tuberculosis complex bacteria (Mtb), the cause of TB, and nontuberculous mycobacteria (NTM) are public health concerns, responsible for global burdens of (extra)pulmonary infection. Drug resistance (DR) further complicates treatment and control. Whole-genome sequencing (WGS) of Mtb can identify mutations associated with resistance to 17 anti-TB drugs, define sub-lineages linked to virulence, and support phylogenetic analyses of transmission. In contrast, the biology, DR mechanisms, and transmission dynamics of NTM are poorly understood.

You will use WGS, including Oxford Nanopore long-read sequencing, to characterise the genomic diversity of Mtb and NTM species, including M. avium and M. abscessus complexes. Integrating genomic data across species, you will identify genetic determinants of DR, develop AI models for genotypic DR prediction, and investigate transmission using strain-relatedness to support improved diagnostics, surveillance, and clinical management.