MRes Infectious & Tropical Diseases - Pathogen Biology

ID	Title	Overview
PB1	Dissecting the antibacterial role of the Campylobacter jejuni T6SS and its effectors. (London)	Campylobacter jejuni is a leading bacterial cause of gastroenteritis, yet the mechanisms enabling it to colonise hosts and compete within microbial communities remain incompletely understood. Our research has identified a Type VI secretion system (T6SS) and associated antibacterial effectors in several C. jejuni lineages. This project will investigate how the T6SS and its effectors contribute to bacterial competition and niche establishment. Using established strains and mutants, you will examine T6SS-dependent competitive fitness under relevant environmental and host-associated conditions. The project may combine bacterial competition assays, molecular microbiology, gene-expression analysis and bioinformatic investigation of T6SS diversity. The work will advance our understanding of C. jejuni survival and adaptation while providing training in bacterial pathogenesis, experimental design and quantitative data analysis.
PB2	Investigating menaquinone-mediated re-sensitisation of drug-resistant tuberculosis. (London)	Bedaquiline is a cornerstone of drug-resistant TB treatment, but resistance is emerging. We have discovered that disrupting menaquinone biosynthesis can restore bedaquiline activity against resistant M. tuberculosis – could the same strategy enhance other TB drugs? This project will investigate whether this vulnerability can be exploited more broadly to enhance future TB treatment regimens. Using in vitro models, you will test whether menaquinone inhibition enhances clinical drugs, compounds in development and drug combinations. You will generate genetic tools to investigate the underlying mechanisms and test these interactions under host-relevant conditions, including altered carbon sources, acidic pH and hypoxia, which profoundly influence bacterial physiology and drug susceptibility. Together, this work will determine whether targeting bacterial energy metabolism could provide a new strategy to improve TB treatment and combat drug resistance.
PB3	High-content imaging of antibiotic effects on Treponema pallidum. (London)	Treponema pallidum (TP), the syphilis spirochete, is an unusual, difficult-to-culture bacterium with a spiral shape and complete dependence on the host. TP requires mammalian cells for growth, making antimicrobial susceptibility testing impossible by standard methods. Current methods rely mainly on identifying resistance-associated mutations or co-culture assays using qPCR to monitor bacterial growth. This project aims to identify morphological and phenotypic changes at the single-cell level at scale after antimicrobial exposure using high-content imaging (HCI) and live imaging. You will optimize the HCI platform and use it to characterize responses across TP strains, antibiotic classes, concentrations and exposure durations, and assess survivors and recovery after drug withdrawal to better understand persistence and tolerance. Finally, you will determine whether recently discovered distinct TP subpopulations that colonize the host differ in survival after antimicrobial exposure.
PB4	Catch me if you can: How intracellular bacteria evade host detection. (London)	Some intracellular bacterial pathogens (including Burkholderia and Shigella) replicate successfully within host cells despite triggering potent immune responses. Our group investigates how cells recognise and restrict intracellular pathogens through cell-autonomous immunity (CAI). Despite intense investigation, how a subpopulation of bacteria evades CAI is largely unknown. This project will combine advanced microscopy techniques and state-of-the-art infection models to uncover novel bacterial evasion strategies. Key approaches include: Engineering reporter strains to track bacterial virulence factors in real time Super-resolution microscopy, single-cell imaging and high-content screening Infection assays using cell-free systems, tissue culture cells and zebrafish models Understanding bacterial interactions with CAI could reveal new ways to enhance immune responses, with potential to transform therapeutic treatment of bacterial infections and other diseases linked to CAI dysfunction.
PB5	Drug resistance by dormancy: How do trypanosomes sleep and avoid elimination? (London)	The American trypanosome, Trypanosoma cruzi, causes Chagas disease, a debilitating infection that leads to cardiac and/or gut pathology, often with fatal outcomes. >6 million people are infected, and treatment is restricted to two toxic drugs with limited efficacy. Treatment failure results when a sub-population of parasites switch to a non-replicating form. We have developed a method for isolating these quiescent trypanosomes. The project aims are to dissect the signalling pathways that trigger quiescence and to generate parasite lines where the phenotype is inducible. You will use genetic manipulation techniques to identify and characterise genes that drive reduced DNA replication, transcription and metabolic activity. The parasite lines generated will be integrated into the drug development pipeline to aid identification of novel chemical entities that can eliminate these persister parasites.
PB6	Temporal patterns of cercarial shedding and sex ratios in Bulinus infected with Schistosoma haematobium. (London)	Cercarial shedding by infected snails is essential for schistosomiasis transmission, yet how shedding patterns and parasite sex representation vary throughout infection remains poorly understood. Building on the established snail colonies, parasite strains and expertise developed through the Schistosome and Snail Resource (SSR), this project will investigate cercarial shedding dynamics in Bulinus snails infected with Schistosoma haematobium. You will monitor cercarial output over time and use molecular techniques to determine parasite sex at different stages of infection. The study will explore whether collection timing influences the detection of male and female parasites and the reliability of sex-ratio estimates. Findings will improve our understanding of cercarial shedding dynamics and help optimise sampling strategies for laboratory-maintained schistosome life cycles.
PB7	Bacterial expression, enzyme kinetics and protein structure of a novel malaria lactate dehydrogenase. (London)	Development of malaria parasites (genus Plasmodium) relies on glycolysis to generate energy, which requires pyruvate to lactate conversion by an essential lactate dehydrogenase enzyme (LDH1). We have recently shown that malaria parasites encode a second putative LDH (LDH2) that is critical for parasite transmission by mosquitoes. LDH2 is distinct from LDH1 and human LDH with respect to its catalytic residues and substrate specificity loop, making it an attractive drug target. The project aims to determine the enzymatic properties and 3D structure of LDH2 to see how it differs from Plasmodium LDH1 and human LDH to inform the search for specific inhibitors. The project’s objectives are to: (1) Recombinantly express Plasmodium LDH2 in bacteria; (2) Conduct in vitro enzymatic assays of affinity-purified LDH2 to determine its substrate binding affinities and enzyme kinetics; (3) Carry out 3D structural studies of purified LDH2 via X-ray crystallography or cryo-EM (time allowing).
PB8	Variation in parasite sexual commitment for transmission of malaria in The Gambia. (The Gambia)	Malaria parasites in the blood are mostly asexual but must produce sexual forms to infect mosquitoes. There is significant variation in sexual commitment rates of different clinical isolates of the major human parasite Plasmodium falciparum, ranging from less than 3% up to almost 15% per replicative cycle. The significance and mechanisms of this parasite variation need to be more clearly understood. Parasites have been under natural selection in The Gambia over several decades, during which the level of malaria transmission has declined. This project will investigate variation in sexual commitment of parasite isolates collected over 20 years in The Gambia, and explore the dependence on genomic and epigenetic variation, and the relation to asexual multiplication.
PB9	How do Plasmodium falciparum male gametocytes support the fastest DNA replication in existence? (London)	Plasmodium is the single cell parasite that causes malaria. It cycles between human and mosquito hosts. Transmission from humans to mosquitoes is exclusively mediated by the gametocyte stage of the parasite life cycle. These male and female gametocytes take 8-10 days to develop before becoming dormant waiting for a mosquito to bite. However, within seconds of uptake by a mosquito, the gametocytes sense their change in environment and rapidly differentiate into gametes. Male gametocytes make the most striking differentiation – transforming into eight motile sperm-like gametes. One cell becoming eight requires three rounds of genome replication which is achieved in less than 5 minutes – the fastest rate currently known in existence. How does the parasite achieve this? This project will aim to determine where the "raw materials" for this DNA replication come from - are they already present, or do they need to be made-to-order?
PB10	Molecular epidemiology and biology of a newly-discovered cryptic malaria parasite population. (London)	Most human malaria is caused by Plasmodium falciparum in Africa, but there is much remaining to be discovered about the biology and genetics of this species. In 2024, a distinctive P. falciparum sub-population was discovered, termed the AF1 ‘cryptotype’, comprising ~1–2% of malaria parasites across most African countries. These cryptotype parasites share highly differentiated variant alleles at many genomic regions in strong association across multiple chromosomes, forming a characteristic genetic background. The affected genomic regions include genes involved in erythrocyte invasion, host-cell remodelling and antigen export. Phenotypic analysis of the cryptotype parasites is now a priority for discovery research. Another major question is how this distinct but widely distributed genetic type is maintained despite recombination expected to occur with other P. falciparum parasites? This project offers the option to investigate phenotypes or aspects of the population genomics, or both.
PB11	Characterisation of novel erythrocyte invasion genes in the malaria parasite Plasmodium knowlesi. (London)	Malaria is a deadly disease caused by Plasmodium parasites. During the asexual blood stage, the parasite invades the red blood cell (RBC), multiplies within and releases daughter cells ready to invade new RBCs. Invasion is critical for parasite survival and invasion proteins are key players in host cell tropism, virulence and as vaccine candidates. Whilst most cases are caused by Plasmodium falciparum (Pf) and P. vivax (Pv), the zoonotic parasite P. knowlesi (Pk), has proven an excellent model to understand invasion due to the larger invasive stages and efficiency of genome-editing tools. The aim of this project is to characterise novel invasion genes in Pk parasite, with a view to understand both shared and divergent approaches to invasion across human infective species. Cutting edge techniques include CRISPR-Cas9 gene editing, expansion microscopy and live cell imaging to characterise 1) localisation 2) essentiality and 3) the role of selected invasion protein candidates.

Title

Overview

PB1

Dissecting the antibacterial role of the Campylobacter jejuni T6SS and its effectors.

(London)

Campylobacter jejuni is a leading bacterial cause of gastroenteritis, yet the mechanisms enabling it to colonise hosts and compete within microbial communities remain incompletely understood. Our research has identified a Type VI secretion system (T6SS) and associated antibacterial effectors in several C. jejuni lineages. This project will investigate how the T6SS and its effectors contribute to bacterial competition and niche establishment.

Using established strains and mutants, you will examine T6SS-dependent competitive fitness under relevant environmental and host-associated conditions. The project may combine bacterial competition assays, molecular microbiology, gene-expression analysis and bioinformatic investigation of T6SS diversity. The work will advance our understanding of C. jejuni survival and adaptation while providing training in bacterial pathogenesis, experimental design and quantitative data analysis.

PB2

Investigating menaquinone-mediated re-sensitisation of drug-resistant tuberculosis.

(London)

Bedaquiline is a cornerstone of drug-resistant TB treatment, but resistance is emerging. We have discovered that disrupting menaquinone biosynthesis can restore bedaquiline activity against resistant M. tuberculosis – could the same strategy enhance other TB drugs?

This project will investigate whether this vulnerability can be exploited more broadly to enhance future TB treatment regimens. Using in vitro models, you will test whether menaquinone inhibition enhances clinical drugs, compounds in development and drug combinations. You will generate genetic tools to investigate the underlying mechanisms and test these interactions under host-relevant conditions, including altered carbon sources, acidic pH and hypoxia, which profoundly influence bacterial physiology and drug susceptibility.

Together, this work will determine whether targeting bacterial energy metabolism could provide a new strategy to improve TB treatment and combat drug resistance.

PB3

High-content imaging of antibiotic effects on Treponema pallidum.

(London)

Treponema pallidum (TP), the syphilis spirochete, is an unusual, difficult-to-culture bacterium with a spiral shape and complete dependence on the host. TP requires mammalian cells for growth, making antimicrobial susceptibility testing impossible by standard methods. Current methods rely mainly on identifying resistance-associated mutations or co-culture assays using qPCR to monitor bacterial growth.

This project aims to identify morphological and phenotypic changes at the single-cell level at scale after antimicrobial exposure using high-content imaging (HCI) and live imaging. You will optimize the HCI platform and use it to characterize responses across TP strains, antibiotic classes, concentrations and exposure durations, and assess survivors and recovery after drug withdrawal to better understand persistence and tolerance. Finally, you will determine whether recently discovered distinct TP subpopulations that colonize the host differ in survival after antimicrobial exposure.

PB4

Catch me if you can: How intracellular bacteria evade host detection.

(London)

Some intracellular bacterial pathogens (including Burkholderia and Shigella) replicate successfully within host cells despite triggering potent immune responses. Our group investigates how cells recognise and restrict intracellular pathogens through cell-autonomous immunity (CAI). Despite intense investigation, how a subpopulation of bacteria evades CAI is largely unknown.

This project will combine advanced microscopy techniques and state-of-the-art infection models to uncover novel bacterial evasion strategies. Key approaches include:

Engineering reporter strains to track bacterial virulence factors in real time
Super-resolution microscopy, single-cell imaging and high-content screening
Infection assays using cell-free systems, tissue culture cells and zebrafish models
Understanding bacterial interactions with CAI could reveal new ways to enhance immune responses, with potential to transform therapeutic treatment of bacterial infections and other diseases linked to CAI dysfunction.

PB5

Drug resistance by dormancy: How do trypanosomes sleep and avoid elimination?

(London)

The American trypanosome, Trypanosoma cruzi, causes Chagas disease, a debilitating infection that leads to cardiac and/or gut pathology, often with fatal outcomes. >6 million people are infected, and treatment is restricted to two toxic drugs with limited efficacy. Treatment failure results when a sub-population of parasites switch to a non-replicating form. We have developed a method for isolating these quiescent trypanosomes.

The project aims are to dissect the signalling pathways that trigger quiescence and to generate parasite lines where the phenotype is inducible. You will use genetic manipulation techniques to identify and characterise genes that drive reduced DNA replication, transcription and metabolic activity. The parasite lines generated will be integrated into the drug development pipeline to aid identification of novel chemical entities that can eliminate these persister parasites.

PB6

Temporal patterns of cercarial shedding and sex ratios in Bulinus infected with Schistosoma haematobium.

(London)

Cercarial shedding by infected snails is essential for schistosomiasis transmission, yet how shedding patterns and parasite sex representation vary throughout infection remains poorly understood.

Building on the established snail colonies, parasite strains and expertise developed through the Schistosome and Snail Resource (SSR), this project will investigate cercarial shedding dynamics in Bulinus snails infected with Schistosoma haematobium. You will monitor cercarial output over time and use molecular techniques to determine parasite sex at different stages of infection. The study will explore whether collection timing influences the detection of male and female parasites and the reliability of sex-ratio estimates. Findings will improve our understanding of cercarial shedding dynamics and help optimise sampling strategies for laboratory-maintained schistosome life cycles.

PB7

Bacterial expression, enzyme kinetics and protein structure of a novel malaria lactate dehydrogenase.

(London)

Development of malaria parasites (genus Plasmodium) relies on glycolysis to generate energy, which requires pyruvate to lactate conversion by an essential lactate dehydrogenase enzyme (LDH1). We have recently shown that malaria parasites encode a second putative LDH (LDH2) that is critical for parasite transmission by mosquitoes. LDH2 is distinct from LDH1 and human LDH with respect to its catalytic residues and substrate specificity loop, making it an attractive drug target.

The project aims to determine the enzymatic properties and 3D structure of LDH2 to see how it differs from Plasmodium LDH1 and human LDH to inform the search for specific inhibitors. The project’s objectives are to: (1) Recombinantly express Plasmodium LDH2 in bacteria; (2) Conduct in vitro enzymatic assays of affinity-purified LDH2 to determine its substrate binding affinities and enzyme kinetics; (3) Carry out 3D structural studies of purified LDH2 via X-ray crystallography or cryo-EM (time allowing).

PB8

Variation in parasite sexual commitment for transmission of malaria in The Gambia.

(The Gambia)

Malaria parasites in the blood are mostly asexual but must produce sexual forms to infect mosquitoes. There is significant variation in sexual commitment rates of different clinical isolates of the major human parasite Plasmodium falciparum, ranging from less than 3% up to almost 15% per replicative cycle. The significance and mechanisms of this parasite variation need to be more clearly understood.

Parasites have been under natural selection in The Gambia over several decades, during which the level of malaria transmission has declined. This project will investigate variation in sexual commitment of parasite isolates collected over 20 years in The Gambia, and explore the dependence on genomic and epigenetic variation, and the relation to asexual multiplication.

PB9

How do Plasmodium falciparum male gametocytes support the fastest DNA replication in existence?

(London)

Plasmodium is the single cell parasite that causes malaria. It cycles between human and mosquito hosts. Transmission from humans to mosquitoes is exclusively mediated by the gametocyte stage of the parasite life cycle. These male and female gametocytes take 8-10 days to develop before becoming dormant waiting for a mosquito to bite. However, within seconds of uptake by a mosquito, the gametocytes sense their change in environment and rapidly differentiate into gametes. Male gametocytes make the most striking differentiation – transforming into eight motile sperm-like gametes. One cell becoming eight requires three rounds of genome replication which is achieved in less than 5 minutes – the fastest rate currently known in existence. How does the parasite achieve this?

This project will aim to determine where the "raw materials" for this DNA replication come from - are they already present, or do they need to be made-to-order?

PB10

Molecular epidemiology and biology of a newly-discovered cryptic malaria parasite population.

(London)

Most human malaria is caused by Plasmodium falciparum in Africa, but there is much remaining to be discovered about the biology and genetics of this species.

In 2024, a distinctive P. falciparum sub-population was discovered, termed the AF1 ‘cryptotype’, comprising ~1–2% of malaria parasites across most African countries. These cryptotype parasites share highly differentiated variant alleles at many genomic regions in strong association across multiple chromosomes, forming a characteristic genetic background. The affected genomic regions include genes involved in erythrocyte invasion, host-cell remodelling and antigen export.

Phenotypic analysis of the cryptotype parasites is now a priority for discovery research. Another major question is how this distinct but widely distributed genetic type is maintained despite recombination expected to occur with other P. falciparum parasites? This project offers the option to investigate phenotypes or aspects of the population genomics, or both.

PB11

Characterisation of novel erythrocyte invasion genes in the malaria parasite Plasmodium knowlesi.

(London)

Malaria is a deadly disease caused by Plasmodium parasites. During the asexual blood stage, the parasite invades the red blood cell (RBC), multiplies within and releases daughter cells ready to invade new RBCs. Invasion is critical for parasite survival and invasion proteins are key players in host cell tropism, virulence and as vaccine candidates.

Whilst most cases are caused by Plasmodium falciparum (Pf) and P. vivax (Pv), the zoonotic parasite P. knowlesi (Pk), has proven an excellent model to understand invasion due to the larger invasive stages and efficiency of genome-editing tools. The aim of this project is to characterise novel invasion genes in Pk parasite, with a view to understand both shared and divergent approaches to invasion across human infective species. Cutting edge techniques include CRISPR-Cas9 gene editing, expansion microscopy and live cell imaging to characterise 1) localisation 2) essentiality and 3) the role of selected invasion protein candidates.