Dr. Maddie Moule

Chancellor's Fellow - Global Challenges

  • Institute of Immunology and Infection Research
  • School of Biological Sciences

Contact details

Address

Street

Ashworth Laboratories
Charlotte Auerbach Road
The King's Buildings

City
Edinburgh
Post code
EH9 3FL

Biography

Background

2010 Ph.D. Microbiology and Immunology, Stanford Univerity

2010-2014 Research Fellow, London School of Hygiene and Tropical Medicine

2014-2020 Postdoctoral Research Fellow, Texas A&M Univeristy

2020- present Chancellor's Fellow, University of Edinburgh 

Research summary

Bacterial pathogens have evolved a diverse range of strategies to infect, survive, and replicate within a host. Dissecting the interactions between bacteria and their hosts can help us understand how pathogens cause disease and facilitate the developments of novel diagnostics and therapeutics to treat human disease. The overarching goal of my research is to study bacterial host-pathogen interactions by identifying novel bacterial virulence factors using large-scale genetic screens and characterizing the mechanisms through which these virulence factors interact with host cells using air-liquid interface cultures and three-dimensional tissue culture models more accurately represent the human lung. My research addresses the global challenges facing human health with specific focus on:

  • The dissemination and extrapulmonary spread of Mycobacterium tuberculosis, one of the leading causes of death by infectious disease worldwide. While tuberculosis is primarily a respiratory disease, up to 15% of M. tuberculosis cases are extrapulmonary infections that are particularly difficult to diagnose and treat. The mechanisms of M. tuberculosis dissemination are unknown, but it is thought that M. tuberculosis is able to breach the barrier of the alveolar epithelium either by directly infecting epithelial cells or by transiting across the epithelia within macrophages or dendritic cells. Using a technique known as TraDIS to screen a library of bacterial mutants in a guinea pig model, I have identified a panel of potential M. tuberculosis dissemination mutants. To characterize these virulence factors, I developed and applied three-dimensional tissue culture models of the alveolar barrier including air-liquid interface (ALI) cultures, and spheroid cultures
  • The pathogenesis and vaccine target identification of Burkholderia pseudomallei, the causative agent of melioidosis. Melioidosis a neglected tropical disease that is endemic to Southeast Asia and Northern Australia. It is also listed as a Tier 1 select agent and potential bioterrorism threat, meaning that development of a protective vaccine is a research imperative. I previously performed a TraDIS screen for B. pseudomallei virulence factors, which we have re-analyzed to identify dissemination factors similar to those identified in M. tuberculosis. Characterizing these genes will help us to better understand this emerging threat and identify potential targets for the development of new vaccines and therapeutics.
  • Screening novel antimicrobials against the ESKAPE pathogens with the goal of filling the clinical need created by the emergence of antibiotic resistance. The ESKAPE pathogens are a group of bacterial pathogens including Staphylococcus aureus and Pseudomonas aeruginosa that are leading causes of nosocomial infections throughout the world due to the emergence of antibiotic resistance strains. The models I have developed to study dissemination have also proven to be valuable tools for testing and characterizing new therapeutics such as antimicrobial peptoids that can help address the urgent clinical need for new strategies against these pathogens.

View all 9 publications on Research Explorer

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