Dr Russell Collighan

Supervisor Details

Contact Details

Scientific Background

Research Interests

Our research is focussed on a group of enzymes called transglutaminases. Transglutaminases are found in many different organisms including microbes, plants and mammals. These enzymes are responsible for a variety of post-translational modifications of proteins, in particular cross-linking of proteins into large molecular weight polymers that are more resistant to degradation. In higher organisms such as mammals, this process is important for the stability of skin, hair, blood clots and the extracellular matrix surrounding cells. In spore-forming bacteria, they cross-link spore coat proteins to enhance spore stability to environmental factors such as heat and chemicals, including antibiotics.

We are interested in elucidating the contribution that transglutaminases have to the stability of structures such as spores and/or the cell wall in clinically-relevant bacteria eg Clostridium difficile and Pseudomonas aeruginosa, respectively. This knowledge is important for understanding survival and defence mechanisms and may lead to identification of novel antimicrobial targets.

Scientific Inspiration

There are so many to choose from, but I would probably say Leonardo da Vinci. Like many great scientists, he was unaware of how far ahead of his time his ideas were. He was curiosity-driven and saw the beauty of art, engineering and science together.

Supervision Style

In three words or phrases: laid-back, technique-orientated, student-centred.

Provision of Training

I will take responsibility for your technical training from the outset, guiding you to more independence when you are ready. I will foster your curiosity and encourage you to apply your problem-solving skills. My goal is for you to develop into a confident and capable independent researcher with the necessary skills to succeed in any research career.

Progression Monitoring and Management

We will meet weekly to discuss progress and plan experimental work. Consideration of your data and critical discussion of your methodologies will enable you to take more ownership of the design and direction of your experiments. I will guide you in the larger picture, so that you can consolidate your work into a coherent thesis and a successful defence.

Communication

I am happy to discuss any issues related to your work and research education at any time. My door is always open and I will always be supportive.

PhD Students can expect scheduled meetings with me.

In a group meeting	In year 1 of PhD study	In year 2 of PhD study	In year 3 of PhD study
At least once a week	At least once a week	At least once a week	At least once a week

These meetings will mainly be 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

Current Projects (2025-26)

Primary supervisor for:

Inhibition of Pseudomonas aeruginosa TgpA as a novel antimicrobial strategy

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).

Inhibition of Pseudomonas aeruginosa TgpA as a novel antimicrobial strategy

Secondary Supervisor(s): Dr John Simms

University of Registration: Aston University

BBSRC Research Themes:

Understanding the Rules of Life (Microbiology)
Integrated Understanding of Health (Pharmaceuticals)

Project Outline

Healthcare-acquired infections (HCAI) are a major problem in hospitals throughout the world, costing the NHS more than £1 billion per annum [1]. A large proportion of these infections are due to an opportunistic bacterial pathogen, Pseudomonas aeruginosa. P. aeruginosa is responsible for many respiratory tract infections in hospitals, in particular pneumonia. Whilst healthy individuals are usually unaffected or recover well, seriously ill patients or those whose immune systems are not fully functional are more susceptible. In these cases, the infection is usually very serious and mortality rates can be as great as 70%. P. aeruginosa is particularly important for cystic fibrosis (CF) patients who cannot clear mucus in their airways efficiently. CF sufferers typically contract chronic infections which cause permanent lung damage and this is the principal cause of morbidity and mortality. P. aeruginosa infection is difficult to control because it tends to be resistant to many antimicrobial agents. There exists an urgent need for novel antimicrobials to aid control of P. aeruginosa infection.

A protein, TgpA, that is essential for the growth of P. aeruginosa has been identified [2]. It is thought to be involved in cell wall production, which is a common target for existing antibiotics. TgpA is an integral inner membrane protein with a periplasmic domain that has transglutaminase (TG) activity and can therefore cross-link proteins together to create stable structures. It is likely that TgpA catalyses the modification of an existing cell wall component or stabilises the cell wall by cross-linking of proteins [2]. This project will screen commercially available TG inhibitors to identify compounds that can inhibit P. aeruginosa TgpA, with a view to identifying a novel class of potential antimicrobials. The crystal structure of the periplasmic TG domain of TgpA has been solved, allowing the opportunity for SAR based drug design [3]. This could allow development of these inhibitors into effective antibiotics against P. aeruginosa. Identification of a novel class of antibiotics could also allow this strategy to be adopted in other microorganisms that also use TGs for growth or virulence.

A further aspect of the project is to use molecular modelling to understand TgpA cross-linking and substrate selectivity. This will use various computational methods, including homology modelling, molecular docking, and molecular dynamics simulations, to construct and analyse 3D models of TgpA. These models will simulate enzyme-substrate interactions, explore the structural basis of substrate specificity, and elucidate the mechanisms of peptidoglycan binding and cross-linking. The molecular modelling will complement the molecular biology-based approach to gain a deep understanding of the structure and function of TgpA.

Objectives

1. Recombinant expression of TgpA in E. coli and affinity purification.

2. Characterisation of recombinant TgpA substrate specificity.

3. Perform in silico studies to predict TgpA substrate/inhibitor binding.

4. In vitro screening of recombinant TgpA with potential inhibitors.

5. Test active compounds for growth inhibition of P. aeruginosa.

References

[1] Plowman R, Graves N, Griffin M, Roberts JA, Swan A, Cookson B, Taylor L. The socio-economic burden of hospital acquired infection. London: PHLS, 2000.

[2] Milani A, Vecchietti D, Rusmini R, Bertoni G (2012). TgpA, a protein with a eukaryotic-like transglutaminase domain, plays a critical role in the viability of Pseudomonas aeruginosa. PLoS One 7(11):e50323.

[3] Uruburu M, Mastrangelo E, Bolognesi M, Ferrara S, Bertoni G, Milani M (2019). Structural and functional characterization of TgpA, a critical protein for the viability of Pseudomonas aeruginosa. Journal of Structural Biology 205(3):18-25.