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Dr Patrick Moynihan

Supervisor Details

Dr Patrick Moynihan

Contact Details

Dr Patrick Moynihan

School of Biosciences, University of Birmingham

Dr Moynihan is a Senior Research Fellow and BBSRC David Phillips Fellow in the School of Biosciences. 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.

Research Interests

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.


Project Details

Dr Moynihan is supervisor for the below project:

Uncovering the regulatory systems governing mycobacterial cell division

Secondary Supervisor(s):Professor David Grainger

University of Registration:University of Birmingham

BBSRC Research Themes:

Apply here!

Deadline: 4 January, 2024


Project Outline

Few diseases have had a more significant impact on human health than tuberculosis. This on-going pandemic claims 1.6 million lives annually and is the 13th leading cause of death world-wide according to the WHO. The biology of tuberculosis is marked by a complex and multi-stage inflammatory process driven by Mycobacterium tuberculosis. The cell envelope of these bacteria acts as the major interface between the host and pathogen. This structure is dominated by a macromolecule comprised of mycolic acids, arabinogalactan, and peptidoglycan with many intercalated lipids such as lipoarabinomannan (LAM). These molecules, or fragments of them, serve as important signals to the host, driving complex interactions at once provoking and inhibiting inflammatory responses. What is less well understood is that fragments of these structures also serve as important signals for the bacteria. In this project the student will take advantage of our recent discovery of new cell wall degrading enzymes and use omics-methods such as RNAseq and proteomics to identify the regulatory pathways driven by the action of these enzymes. The student will gain experience in biochemistry, microbiology, proteomics, RNAseq and the bioinformatic tools required for the analysis of their data. They can also engage in structural biology and molecular microbiology, as the needs of the project or their personal interest require..

Techniques

My laboratory employs a wide range of techniques to answer fundamental questions about bacterial biology (see: https://www.nature.com/articles/s41467-019-10586-2; https://www.nature.com/articles/s41467-023-37839-5). In this project the student will tackle their research question from two main directions. First, they will gain experience cultivating mycobacteria and optimising phenotypic responses to cell wall metabolites, some of which we have already preliminarily established. This will involve working with high-throughput robotics and biochemical techniques. The student will then investigate these phenotypes through approaches such as RNASeq or proteomics. Finally the student can investigate proteins of interest through biochemistry by recombinantly producing and purifying target proteins and structural biology techniques including X-ray crystallography. The student can also investigate function through bacterial cell biology using knock-out strains of the bacteria, making use of fluorescent probes and a range of analytical techniques including mass spectrometry.


Previous Projects

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