Christopher McDevitt

Christopher McDevitt

School of Biological Sciences

Faculty of Sciences

Eligible to supervise Masters and PhD - email supervisor to discuss availability.

Membrane proteins account for about one-third of the proteins encoded by every genome but, in contrast to soluble proteins, they are poorly characterised. The research in my laboratory, based in the Research Centre for Infectious Diseases (RCID), investigates how the integral membrane protein ATP-binding cassette (ABC) transporters contribute to the virulence of the major human pathogens Streptococcus pneumoniae (responsible for >1 million deaths annually) and Staphylococcus aureus (a health care burden of >$1 billion AUS annually). My work has already made major advances in our understanding of how metal ion ABC transporters contribute to the virulence of these pathogens and the chemical biology of the host-pathogen interface. By understanding how these transporters function, our work is also providing the foundation for translating basic science into effective antimicrobial therapies. Notably, our research has already identified a molecular role for zinc in resisting bacterial infection, which is highly important as nearly 2 billion people are zinc deficient, and demonstrated the potential to exploit these ABC uptake transporters as antimicrobial targets due to their essential requirement for bacterial virulence, a complete lack of human homologs, and their highly exposed and accessible location on the bacterial cell-surface.

The long-term goal of my research is to target these metal ion transporters with next generation antimicrobials, which will save over 1 million lives annually. My research to achieve this goal is focused, first on elucidating how bacterial pathogens, e.g. S. pneumoniae, facilitate metal ion homeostasis, and second how we can target these mechanisms to attenuate virulence in the host environment. To this end we will continue to study the structure/function relationships of how these metal recruiting proteins work and then exploit our cutting edge knowledge, in which we are acknowledged world-leaders, to develop the next generation of antimicrobial therapeutic agents.

The projects in my laboratory ( which are now based at the University of Melbourne are focused on studying metal ion transporters of pathogenic bacteria. Bacterial infections are highly dependent on metal ion micronutrients. The high affinity metal ion uptake pathways are transporters called ATP-binding cassette (ABC) permeases. These transporters acquire metal ions from the extracellular host environment. Of particular interest to our group are the metal ions zinc and manganese, the second and third most abundant transition metal ions in living organisms. Manganese has essential roles during infection and colonization, where it serves in carbon metabolism and oxidative stress response. Zinc is a vital cofactor for numerous host and bacterial cellular functions. The manganese and zinc ABC uptake transporters have been shown to be essential for the virulence of a number of human pathogens including Streptococcus pneumoniae.

1. Manganese uptake in Streptococcus pneumoniae and other pathogens

Bacterial pathogens must scavenge their metal ions from the host environment in order to mediate virulence. Streptococcus pneumoniae is the world's foremost bacterial pathogen and is responsible for more than one million deaths every year. In terms of relative disease burden, it is the largest bacterial killer of young children and kills more children every year than AIDs, tuberculosis and malaria combined. However, its ability to infect and cause disease are dependent on the acquistion of metal ions, one of which is the transition row metal ion manganese. Loss of manganese uptake completely prevents its ability to cause disease.

PsaA transition to closed state
Apo-PsaA transition to closed metal-bound conformation.

Our group seeks to understand how S. pneumoniae, and other pathogens, scavenge manganese from the host environment. Although it was known an ABC importer was involved in this process, the underlying details were pooly understood. Recently we revealed the mechanism by which S. pneumoniae scavenges manganese from the host environment and how another metal ion, zinc, interfered with this process. We found that the manganese recruiting protein, PsaA, used a 'spring-hammer' mechanism to bind metal ions, in which half of the protein pivoted and closed over the other half.

There are still many unanswered questions that we are currently investigating. These include how is this ABC importer is selective for manganese ions, how are these ions are translocated into the bacterial cell, and how does the host prevent manganese from being scavenged by the bacteria during infection. Answering these questions will provide the necessary information to design the next generation of antimicrobial agents to target this essential bacterial pathway.

2. Zinc homeostasis in Streptococcus pneumoniae

Zn homeostasis mechanisms of S. pneumoniae
Zn homeostasis mechanisms of S. pneumoniae

Zinc is the second most abundant transition row element in biological systems. This metal ion has crucial roles in numerous cellular processes such as transcription, translation, catalysis and metabolism. As with all nutrients, pathogenic bacteria must scavenge zinc from the host in order to mediate disease.

Our studies have shown that manganese and zinc have an unusual relationship in S. pneumoniae, where zinc can actually block the manganese ABC importer. So we are seeking to  understand how zinc is acquired and managed in this organism. Recently work from our lab identified that zinc uptake in S. pneumoniae, although similar to manganese uptake, was regulated in a more complex manner. Intriguingly zinc was recruited by 2  proteins, AdcA and AdcAII. A number of possible models have been proposed for how these proteins work together to recruit zinc.

Work in our group is focused on understanding how zinc is sensed by S. pneumoniae, how is zinc managed once it has been translocated into the cell, and how does the host utilise zinc during infection. The answers we obtain to these questions will lead to new ways to target this major human pathogen and its need for zinc.

Research Opportunities

Honours and PhD: My laboratory has 4 multidisciplinary projects on offer in 2020 that combine genetics and biochemistry to study the virulence mechanisms of major bacterial pathogens. A project in my lab will provide you with a strong set of research skills ideally suited for a job in science or further PhD research. These projects are available as studies jointly through the University of Adelaide and the University of Melbourne. For students interested in an opportunity to experience the full breadth of Australian research opportunities, please see my webpage for further details.

  • Appointments

    Date Position Institution name
    2019 Affiliate Associate Professor of Microbiology University of Adelaide
    2018 Associate Professor University of Melbourne
    2017 ARC Future Fellow University of Adelaide, Adelaide
    2017 - 2018 Associate Professor University of Adelaide
    2016 - 2018 Deputy Director, Australian Centre for Antimicrobial Resistance Ecology Universiy of Adelaide
    2016 Faculty Affliate SAHMRI
    2014 - 2018 Deputy Director, Research Centre for Infectious Diseases University of Adelaide
    2012 - 2017 Senior Lecturer in Microbiolgy University of Adelaide
    2008 - 2011 NHMRC Research Fellow University of Adelaide
    2005 - 2008 Senior Research Associate University of Oxford
    2002 - 2005 Research Associate University of Oxford
  • Awards and Achievements

    Date Type Title Institution Name Country Amount
    2011 Award RCDN Mid-Career Research Award The University of Adelaide Australia
    2007 Fellowship EPA Cephalosporin Junior Research Fellow Linacre College, University of Oxford United Kingdom
  • Education

    Date Institution name Country Title
    University of Queensland Australia PhD
    University of Queensland Australia BSc (Hons)
  • Research Interests

Our research is supported by:

National Health and Medical Research Council (NHMRC)
  • Project Grant (CIA) - APP1140554 (2018–20) $843,035
  • Project Grant (CIB) - APP1145075 (2018–21) $784,541
  • Doherty Early Career Fellowship - Dr Stephanie Begg (2018-2021) $322,952
  • Project Grant (CIA) - APP1122582 (2017-2019) $870,924
  • Project Grant (CIB) - APP1080784 (2015-2017) $613,134
  • Project Grant (CIA) - APP1022240 (2012-2014) $568,375
  • Equipment Grant (CIA) - Liquid handling platform (2015) $20,870
  • Equipment Grant (CIA) - qRT-PCR equipment (2014) $40,000
  • Equipment Grant (CIA) - Spectrophotometric equipment - (2012) $35,500
  • Equipment Grant (CIA) - Refrigerated AKTA FPLC - (2011) $62,042
  • Equipment Grant (CIA) - Beckman Coulter Optima Max Biosafe Ultracentrifugation System - (2010) $78,000
  • Equipment Grant (CID) - Cell disruptor system - (2009) $22,000
  • Equipment Grant (CII) - Replacement Purification Systems - (2008) $28,401

Australian Research Council (ARC)

  • Future Fellowship - FT170100006 (2017-2021) $879,617
  • Discovery Project (CIA) - DP170102102 (2017-2019) $605,500
  • Discovery Project (CIB) - DP150104515 (2015-2017) $384,300
  • Discovery Project (CIA) - DP120103957 (2012-2014) $255,000
Channel 7 Children's Research Foundation
  • Project - Dr Bart Eijkelkamp (CIA) and Christopher McDevitt (CIB) - (2016) $35,000
  • Project - Ms Victoria Lewis (CIA) and Christopher McDevitt (CIB) - (2013) $31,000
  • Project (CIA) - (2010-2011) $98,000
Australian Cystic Fibrosis Foundation
  • Postgraduate Studentship Grant - (2011-2013) $15,000
Clive and Vera Ramaciotti Foundation
  • Equipment Grant (Coordinator) - Zetasizer Nano ZSP for protein characterisation and drug discovery - (2013) $54,783
  • Equipment Grant (Coordinator) - Instrumentation for cellular and subcellular analyses - (2012) $67,595
University of Adelaide
  • DVCR IRF Grant (CIE) Accelerating biological discovery through Artificial Intelligence - (2017) $90,000
  • DVCR IRF Grant (CIA) Metalloproteomics infrastructure grant (Bioruptor) - (2015) $50,000
  • DVCR IRF Grant (CIA) Metalloproteomics infrastructure grant (HPLC) - (2015) $28,000
  • IPAS Extending Collaborations Pilot Projects (CIB) - (2014) $16,000
  • IPAS Extending Collaborations Pilot Projects (CIB) - (2013) $8,500
  • DVCR Equipment Grant (CIA) - Temperature controlled shaking incubators - (2012) $81,136
  • DVCR Equipment Grant (CIA) - High speed centrifugation infrastructure - (2012) $365,813
  • Biomed IIA
  • Principles and Practice of Research (Advanced) II
  • Principles and Practice of Research (Advanced) III
  • Infection and Immunity IIA
  • Current Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2016 Principal Supervisor The role of CzcD in Zinc homeostasis Doctor of Philosophy Doctorate Full Time Erin Bridget Brazel
    2016 Co-Supervisor Development of Antibacterial Silver-based Coordination Polymers Doctor of Philosophy Doctorate Full Time Mr Harley Dwane Betts
  • Past Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2014 - 2016 Principal Supervisor The Molecular Mechanisms of Metal Ion Homeostasis in Streptococcus pneumoniae Doctor of Philosophy Doctorate Full Time Dr Stephanie Louise Begg
    2013 - 2017 Principal Supervisor Characterisation of the Zinc Homeostatic Mechanisms of Streptococcus pneumoniae Doctor of Philosophy Doctorate Full Time Miss Jacqueline Rose Morey
    2011 - 2015 Principal Supervisor Characterisation Of The ATP-Binding Cassette Tranporters of Pseudomonas aeruginosa Doctor of Philosophy Doctorate Full Time Dr Victoria Grace Pederick
  • Committee Memberships

    Date Role Committee Institution Country
    2015 - ongoing President Adelaide Protein Group
    2015 - ongoing Member School of Biological Sciences Health, Safety & Wellbeing Committee University of Adelaide
    2015 - ongoing Member School of Biological Sciences Research Committee University of Adelaide Australia
    2013 - ongoing Representative EU COST Action Group - Molecular Machineries for Ion Translocation Across Biomembranes
    2012 - 2015 Treasurer Adelaide Protein Group
  • Memberships

    Date Role Membership Country
    2010 - ongoing Australian Biophysical Society
    2008 - ongoing Australian Society of Biochemistry and Molecular Biology
    2004 - ongoing Representative UK Biochemical Society United Kingdom
  • Editorial Boards

    Date Role Editorial Board Name Institution Country
    2016 - ongoing Member Frontiers in Microbiology
    2016 - ongoing Associate Editor Scientific Reports
    2014 - ongoing Editor Frontiers in cellular and infection microbiology

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