Dr Christopher McDevitt

Biography/ Background

2011 - Present – Group Leader - Membrane Proteins in Bacterial Pathogenesis Laboratory (Discipline of Microbiology and Immunlogy, University of Adelaide)

2008 - 2010 – Independent Research Fellow (Discipline of Microbiology and Immunlogy, University of Adelaide)

2005 - 2008 – Senior Postdoctoral Research Associate (Nuffield Department of Clinical Laboratory Sciences, Oxford)

2002 - 2005 – Postdoctoral Research Associate (Department of Biochemistry, Oxford)

1998 - 2002 – Ph.D (University of Queensland, Australia)

Qualifications

2002 – Ph.D, University of Queensland, Australia.

1997 – Bachelor of Science (Honours, Class I), University of Queensland, Australia.

Awards & Achievements

2011 - Research Career Development Network Mid-Career Researcher Award (University of Adelaide)

2007 - EPA Cephalosporin Junior Research Fellow (Linacre College, University of Oxford)

Research Interests

What are we interested in?

The primary research interest of my group is the role of membrane proteins in bacterial pathogenesis.

Membrane proteins account for about one-third of the proteins encoded by the genome but the challenges in their isolation and handling have meant that they have remained relatively poorly characterised compared to their soluble counterparts.

The focus of research in my group will be to characterise the role of specific membrane proteins and their involvement pathogenicity by mediating bacterial virulence, by use of molecular, biochemical and biophysical techniques.

See the Membrane Proteins in Bacterial Pathogenesis laboratory website for more information.

 

What are we working on?

Metal ion ABC transporters of pathogenic bacteria.

Bacterial infections are highly dependent on metal ion micronutrients. The high affinity uptake pathways are encoded for by ABC permeases that acquire metal ions, such as Mn, Fe, and Zn, from the extracellular environment. These metal ions serve as essential cofactors and activators of biological activity. Of particular interest are the metal ions Mn and Zn. Mn has important roles during initial infection and colonization, in carbon metabolism and oxidative stress response whereas Zn is an important cofactor for a number of different proteins. Importantly, the Mn and Zn ABC permeases have been implicated as virulence determinants in a number of different pathogens.

This project investigates the role of these metal ion transporters, how they bind and transport their metal ligands, and how they facilitate colonization and pathogenicity in the human host.

Characterisation of Pseudomonas aeruginosa ABC transporters

ABC transporters are also associated with multidrug resistance in a broad range of different organisms. There are 4 uncharacterised ABC efflux pumps in P. aeruginosa 3 of which have roles in multidrug resistance. This project will focus on identifying the precise roles and biochemical functions of these proteins and determine whether they contribute to virulence of P. aeruginosa in vivo.

 

A. Colourised scanning electron micrograph of Pseudomonas aeruginosa (Copyright: CDC/Janice Haney Carr)  B. Topology, structure, and conformations of distinct states of type II ABC importers. Philos Trans R Soc Lond B Biol Sci. (2009) 364:239–245

 

What techniques do we use?

These studies utilises a range of different molecular, biochemical and biophysical techniques including:

1. PCR mutagenesis
2. Cloning
   
3. Protein expression
4. Western blotting
5. Biochemical assays
   
6. Thermofluor [what is this?]
   
7. Isothermal titration calorimetry [what is ITC?]
   
8. Circular dichroism spectroscopy [what is CD?]
   

Publications

For the most current publication information, please see my Researcher ID

Key publications relevant to current research

Refereed Journal Articles

1. McDevitt, C.A., Ogunniyi, A.D., Valkov, E., Lawrence, M.C., Kobe, B., McEwan, A.G., and Paton, J.C. (2011) A molecular mechanism for bacterial susceptibility to zinc. PLoS Pathogens 7:e1002357 doi:10.1371/journal.ppat.1002357 [pdf]
2. Ogunniyi, A.D., Mahdi, L.K., Jennings, M.P., McEwan, A.G., McDevitt C.A., Van der Hoek, M.B., Bagley, C.J., Hoffman, P., Gould, K.A., and Paton, J.C. (2010) Central role of manganese in regulation of stress responses, physiology and metabolims in Streptococcus pneumoniae. J. Bacteriol. 192:4489-97. [pdf]
3. McDevitt, C.A., Collins, R.F., Kerr, I.D., and Callaghan, R. (2009) Purification and structural analyses of ABCG2. Adv Drug Del Rev. 61:57-65 [pdf]
4. McDevitt, C.A., Crowley, E.H., Hobbs, G., Starr, K., Kerr, I.D., and Callaghan, R. (2008) Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2? FEBS J. 275:4354-62 [pdf]
5. McDevitt, C.A., Shintre, C.A., Grossmann, G.J., Pollock, N.L., Prince, S.M., Callaghan, R., Ford, R.C. (2008) Structural insights into P-glycoprotein (ABCB1) by small angle X-ray scattering and electron crystallography. FEBS Lett. 582:2950-6 [pdf]
6. McDevitt, C.A., Sargent, F., Palmer, T., and Berks, B. C. (2006) Subunit composition and in vivo substrate-binding characteristics of Escherichia coli Tat protein complexes expressed at native levels. FEBS J. 273:5656-68 [pdf]
7. McDevitt, C.A., Collins R.F., Conway M., Modok S., Storm J., Kerr I.D., Ford R.C. and Callaghan R., (2006) Purification and 3-D structural analysis of oligomeric human multidrug transporter ABCG2. Struct. 14:1623-32 [pdf]
8. Gohlke, U., Pullen, L., McDevitt, C.A., Porcelli, I., Palmer, T., Sabil, H.R. and Berks, B.C. (2005) The TatA component of the twin-arginine protein transport system forms channel complexes of variable diameter. Proc. Natl. Acad. Sci. 102:10482-10486 [pdf]
9. McDevitt, C.A., Hicks, M.G., Palmer, T., and Berks, B.C. (2005) Biochemical characterisation of null phenotype mutant Tat receptor complexes. Biochem. Biophys. Res. Commun. 329:693-8
10. McDevitt, C. A., Hanson, G. R., Noble, C., Cheesman, M. R., and McEwan, A. G. (2002) Characterisation of the redox centres from Dimethylsulfide Dehydrogenase of Rhodovulum sulfidophilum. Biochemistry 41:15234-44
11. McEwan, A.G., Ridge, J.P., McDevitt, C.A., and Hugenholtz, P. (2002) The DMSO reductase family of microbial molybdenum enzymes; molecular properties and role in the dissimilatory reduction of toxic elements. Geomicro. J. 19:3-21
12. McDevitt, C.A., Hugenholtz, P., Hanson, G.R., and McEwan, A.G. (2002) Molecular analysis of Dimethylsulfide Dehydrogenase from Rhodovulum sulfidophilum; its place in the DMSO reductase family of microbial molybdopterin-containing enzymes. Mol. Micro. 44:1575-87

Reviews

1. Lewis, V.G., Ween, M.P., and McDevitt C.A. (2011) The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma. Accepted 29/11/11.
2. Lehane, A.M., McDevitt, C.A., Kirk, K., and Fidock, D.A. (2011) Degrees of chloroquine resistance in Plasmodium - is the redox system involved? Int. J. Paras. Drugs Drug Res. Accepted 02/11/11.
3. Crowley, E. H., McDevitt, C.A., and Callaghan, R. (2009) Generating inhibitors of P-glycoprotein (ABCB1); where to now? In “Multi-Drug Resistance in Cancer” (editor J. Zhou) Methods Mol Bio. 596:405-32 [pdf]
4. McDevitt, C.A., and Callaghan R. (2007) How can we best use structural information on P-glycoprotein to design inhibitors? Pharm and Therap. 113:429-41 [pdf]
5. McEwan, A.G., Kappler, U. and McDevitt, C.A. (2004) Molybdenum enzymes in bacterial respiration. In “Respiration in Archaea and Bacteria” (editor D. Zannoni) Kluwer Academic Publishers. p.175-202

Professional Associations

EU COST - Molecular Machineries for Ion Translocation Across Biomembranes

The Biochemical Society (UK)

The Australian Biochemical and Molecular Biology Society

The European Union Flippase Network

Entry last updated: Wednesday, 19 Sep 2012