Professor Matt O'Shea

Supervisor Details

Contact Details

Scientific Background

Research Interests

My research focuses on clinically important infections and, in particular, the interaction between the human immune system and microbial pathogens. A major area of interest is understanding human immune responses to Mycobacterium tuberculosis, the bacterium that causes tuberculosis, and translating this knowledge into improved diagnostics, treatments and vaccine candidates. My group studies innate and adaptive immunity to mycobacteria, including B-cell, antibody, T-cell and eosinophil responses. We use clinical samples, computational and bioinformatic approaches, and in vivo and ex vivo models to investigate the spectrum from latent tuberculosis infection to active disease. We are also interested in how co-infections, particularly helminth infections, influence immune function and mycobacterial control. Alongside this work, I undertake broader clinically relevant infection research, including infections encountered in military and operational settings. For example, the development of AMR infections associated with combat trauma and how to mitigate against these risks.

Research Groups

Supervision Style

In three words or phrases: Supportive, collaborative, goal-oriented.

Provision of Training

At the beginning of the PhD, I will work with you and the wider supervisory team to identify your training needs and establish a strong foundation in the relevant scientific concepts, laboratory or computational methods, and research governance. As your skills and confidence develop, I will encourage increasing independence while ensuring that appropriate expertise, guidance and opportunities for troubleshooting remain available.

Progression Monitoring and Management

We will agree clear, realistic objectives and review progress regularly against the project鈥檚 scientific aims and formal doctoral milestones. I expect students to take increasing ownership of their work, maintain clear records and raise difficulties early; where progress is slower than anticipated, we will discuss the underlying issues constructively and agree a practical plan of action together.

Communication

I encourage open, professional and two-way communication. Students should feel able to ask questions, discuss unexpected results and raise concerns at an early stage, while recognising that my clinical, academic and military commitments mean that some discussions will need to be scheduled. We will use regular meetings to maintain continuity, and I will make clear when a matter is urgent and which communication method is most appropriate.

Meetings

PhD Students can expect scheduled meetings with me at least once per fortnight. These meetings will be a mixture of face-to-face and via video chat or telephone. I have an open door policy, but my pattern of being contactable for an instant response is not predictable.

Work Patterns

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings) I expect students to manage their own time.

Notice Period for Feedback

I need at least 2 weeks' notice to provide feedback on written work of up to 5,000 words.

MIBTP Project Details

Primary supervisor for:

Host-pathogen compatibility in TB: defining how M.tuberculosis lineage and human ancestry shape TB phenotype, transmission and immune control

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Host-pathogen compatibility in TB: defining how M.tuberculosis lineage and human ancestry shape TB phenotype, transmission and immune control

Secondary Supervisor(s): Prof Adam Cunningham

University of Registration: University of Birmingham

BBSRC Research Themes:

Understanding the Rules of Life (Immunology, Microbiology)

Project Outline

The Mycobacterium tuberculosis complex (MTBC) includes several human-adapted M.tuberculosis (Mtb) lineages with distinct global distributions. L4 (Euro-American) is a widespread generalist, whereas L5 and L6 are restricted to West Africa, suggesting host-pathogen co-adaptation. Matching between Mtb lineage and host ancestry is sympatry; infection with a lineage from a non-overlapping region is allopatry.

Mtb lineage may influence TB phenotype and outcomes. L1 has been linked to extra-pulmonary TB, osteomyelitis and cavitary disease, while outcomes also reflect host factors including age, nutrition, HIV and diabetes. Post-tuberculosis lung disease (PTLD) is a major sequela and WHO research priority. However, the effect of sympatry and allopatry on phenotype, immunology and PTLD remains poorly understood, although limited data suggest allopatric East Asian and Euro-American infections may cause greater pulmonary impairment. Experimental studies suggest ancestry-lineage interactions shape immune responses, with lineage-dependent differences in macrophage uptake, replication and inflammation. Current evidence is limited by small samples, restricted populations, narrow lineage coverage and low-resolution typing, making whole genome sequencing essential.

This project will investigate how Mtb sympatry and allopatry influence transmission, phenotype, outcomes and host immunity. We will analyse national UK WGS-linked datasets over 10 years to estimate TB rates and clinical associations and assess drug resistance, disease site, severity, treatment response, PTLD, transmission and contact immune responses. We will then use ex vivo and in vitro models in healthy donors of defined ancestry, challenging whole blood and immune cells subsets with related and unrelated Mtb lineages and measure mycobacterial control, cytokine responses, immune phenotypes and spatial transcriptomic networks. Potential benefits include advancing TB biology, risk prediction, outcomes and targeted care.

Harnessing trained innate immunity to mitigate hypervirulent multidrug-resistant Klebsiella pneumoniae infection

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Harnessing trained innate immunity to mitigate hypervirulent multidrug-resistant Klebsiella pneumoniae infection

Secondary Supervisor(s): Prof Adam Cunningham

University of Registration: University of Birmingham

BBSRC Research Themes:

Understanding the Rules of Life (Immunology, Microbiology)

Project Outline

Hypervirulent multidrug-resistant Klebsiella pneumoniae (MDR-hvKp) is an emerging threat because it combines invasive disease potential with limited treatment options. Unlike classical K. pneumoniae, hvKp can cause severe infection in otherwise healthy hosts, including pneumonia, bacteraemia, liver abscess and metastatic spread. Its virulence is driven by capsule overproduction, hypermucoviscosity, siderophore-mediated iron acquisition, lipopolysaccharide-related serum resistance and plasmid-encoded factors such as rmpA/rmpA2 and aerobactin genes. Recent studies show that hvKp strains can evade complement deposition and neutrophil uptake, although immune evasion varies by sequence type, capsule biology and resistance background.

This project will investigate whether trained innate immunity can improve host defence against MDR-hvKp. Trained immunity describes long-lasting functional reprogramming of innate immune cells and progenitors, mediated by epigenetic and metabolic changes, leading to enhanced responses to later unrelated infections. BCG is the best-studied inducer and has been associated with increased monocyte, macrophage, NK-cell and neutrophil responsiveness.

The central hypothesis is that BCG-induced trained immunity will enhance early immune control of MDR-hvKp by improving cytokine responses, opsonophagocytosis, neutrophil activation and macrophage antimicrobial activity. The project will compare hvKp and MDR-hvKp isolates with different capsule, virulence and resistance profiles; test trained-immunity effects in human whole-blood and innate-cell models; and identify bacterial and host biomarkers predicting benefit.

The expected output is a mechanistic framework for using trained immunity as an adjunctive mitigation strategy against MDR-hvKp. This could inform future vaccine, immunotherapy or host-directed approaches, while recognising that benefit is likely to depend on strain phenotype and host immune status.

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Midlands Integrative Biosciences Training Partnership