Dr Patrick Moynihan

Supervisor Details

Contact Details

School of Biosciences, University of Birmingham

Scientific Background

Research Interests

His group employs multi-disciplinary approach to study the pathogenic mycobacteria. He is primarily interested in the molecular rules that underpin complex interactions between bacteria and their host, with an emphasis on the modulation of cell wall structures.

The cell wall is the key interface between bacteria and their environment. For a human pathogen like Mycobacterium tuberculosis that environment can be radically different during different stages of infection. The cell wall is comprised of a range of different molecules including a diverse group of complex glycopolymers. As with so many facets of biology, these structures are not static and their shape and composition can determine the outcome of interactions between the bacterium and its host or environment (summarised below). Work in Patrick’s laboratory focuses on how mycobacteria alter their cell wall in response to different environments, and how they turn cell wall structures over to support their growth and division.

All of this work incorporates a broad range of tools, drawn from microbiology, biochemistry, structural biology and analytical chemistry.

Scientific Inspiration

I am inspired by scientists who look for new and creative directions for their research and who want to be able to make a real and lasting impact on the world. A great example of this is Dr Jonas Salk who famously lead the development of the polio vaccine using what was at the time a risky approach. Salk is also widely credited with not seeking monetisation of his vaccine which has unquestionably benefitted all of humanity.

Supervision Style

In three words or phrases: Supportive, student-centred, collaborative.

Provision of Training

Training is a collaborative experience. I want to first understand what my students know and don’t know and then work with them to develop a strategy to learn the techniques and skills they need to succeed. This can be fully independent, or fully one-on-one training but is usually some blend of the two and involves the input of the entire lab.

Progression Monitoring and Management

I prefer to meet with my students frequently to discuss challenges and successes. As a student settles into their work and becomes more independent, I hope that they will take greater ownership of their project and its direction with my support. Within the wider group we operate as a team, with contribution from all members to each project. That can be in the form of simple advice and chatting, or actual experimental support where appropriate.

Communication

My research group uses a variety of tools to connect ranging from messaging systems (Slack mostly) to email, to face-to-face meetings. This is important because problems can be addressed early, which gives someone the best chance at success. I never expect communication outside of working hours, but I am often available if needed outside those hours.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

These meetings will be mainly face to face, and I am usually contactable for an instant response on every working day.

Working Pattern

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 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Previous Projects (2024-25)

Primary supervisor for:

Uncovering the regulatory systems governing mycobacterial cell division

Co-supervisor on a project with Professor Andy Lovering.

Previous Projects (2023-24)

Primary supervisor for:

Characterising the genetic determinants of phage infection in mycobacteria Exploring a unique predator-prey relationship to uncover vulnerabilities in tuberculosis

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Exploring a unique predator-prey relationship to uncover vulnerabilities in tuberculosis

Secondary Supervisor: Professor Andrew Lovering

University of Registration: University of Birmingham

BBSRC Strategic Research Priority: Understanding the Rules of Life (Microbiology)

Project Outline

Life at the microbial scale is a constant battle for resources and territory. Microorganisms can survive in this environment by using many different strategies, including attacking and consuming other bacteria. For example, we have investigated some of the mechanisms by which Bdellovibrio bacteriovorus attacks Gram-negative bacteria1,2. The candidate phyla radiation group of bacteria is a recently discovered collection of organisms including a grouping referred to as “TM7”. Some of these ultra-small bacteria attach themselves to larger organisms, slowing eating them until their host is killed3. In this project the student will exploit the predatory relationship between one of these TM7 bacteria, Candidatus Mycosynbacter amalyticus3, and organisms closely related to Mycobacterium tuberculosis, the causative agent of tuberculosis. The mechanisms underlying this process are poorly understood, though we have recently identified enzymes which this organism uses to break-down the mycobacterial cell wall4. The student will use a high-throughput, systems-biology approach to identify novel effectors produced by this organism, and then characterise them using cutting-edge molecular biology, biochemistry and structural biology approaches. Briefly, the student will conduct a genome-wide screen of Candidatus Mycosynbacter amalyticus to identify the proteins used by this organism to feed upon its mycobacterial host. Identified proteins will be investigated biochemically and structurally, and the mechanism by which they undermine mycobacterial vulnerability will be determined. The student will advance our understanding of this poorly-understood group of organisms while at the same time combatting mycobacterial disease.

References

Harding, C. J. et al. A lysozyme with altered substrate specificity facilitates prey cell exit by the periplasmic predator Bdellovibrio bacteriovorus. Nat Commun 11, 4817 (2020). https://doi.org:10.1038/s41467-020-18139-8
Cadby, I. T. et al. Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase. EMBO J 38, e100772 (2019). https://doi.org:10.15252/embj.2018100772
Batinovic, S., Rose, J. J. A., Ratcliffe, J., Seviour, R. J. & Petrovski, S. Cocultivation of an ultrasmall environmental parasitic bacterium with lytic ability against bacteria associated with wastewater foams. Nat Microbiol 6, 703-711 (2021). https://doi.org:10.1038/s41564-021-00892-1
Al-Jourani, O. et al. Mining the human gut microbiome identifies mycobacterial D-arabinan degrading enzymes. bioRxiv, 2022.2007.2022.500997 (2022). https://doi.org:10.1101/2022.07.22.500997

Techniques

The student will learn: systems biology approaches in microbiology, high-throughput genetic screens, the development of biochemical assays and structural biology. They will also have the opportunity to work in our bio-safety containment level 3 laboratory with pathogenic organisms like Mycobacterium tuberculosis.

CASE: Improving microbial diagnostics through systems biology