Dr Christopher McDevitt

Biography/ Background

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

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

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

2008 – Present – Independent Research Fellow (Department of Microbiology and Immunlogy, University of Adelaide)

Qualifications

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

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

Awards & Achievements

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 will be in 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 in mediating bacterial pathogenicity, by use of molecular, biochemical and biophysical techniques.

 

What are we working on?

Metal ion ABC transporters of Pseudomonas aeruginosa.

ATP-binding cassette (ABC) transporters are one of the largest superfamilies of membrane proteins. In bacteria they are involved in both uptake and efflux pathways of a variety of structurally unrelated molecules. Only in recent years has high resolution structural information become available on this class of proteins.

Pseudomonas aeruginosa is major human pathogen, most notably in cystic fibrosis and other immune compromised conditions. In addition, its large and plastic genome have enabled it to rapidly adapt to changing environmental conditions and antibiotic treatment. As a consequence, new strategies to combating this microorganism are required.

P. aeruginosa infections are highly dependent on metal ion micronutrients. Metal ions, such as Mn, Fe, Mo and Zn, are acquired by high affinity uptake pathways encoded by ABC permeases. These metal ions serve as essential cofactors and activators of biological activity. Of particular interest are the metal ions Mn and Mo. Mn has important roles during initial infection and colonization, in carbon metabolism and oxidative stress response, whilst Mo has crucial roles in anaerobic respiration and metabolism during the later stages of chronic infection. Moreover, the Mn and Mo ABC permeases have been implicated as virulence determinants due to their up-regulation during host colonization.

This project will investigate the role of metal ion transporters in facilitating Pseudomonad colonization and pathogenicity in the human host. 

Characterisation of novel virulence-associated P. aeruginosa membrane proteins

This project will focus on the initial characterisation of a number of membrane proteins identified by microarray and proteomic studies as having a virulence association. The precise roles and functions of these proteins remain to be investigated.

 

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
7. Isothermal titration calorimetry
8. Circular dichroism spectroscopy

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., Collins R.F., Kerr I.D., and Callaghan R. (2009) Purification and structural analyses of ABCG2. Adv Drug Del Rev. 61:57-65 [pdf]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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

8. 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

9. 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

10. 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. 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) Humana Press. In press

2. 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]

3. 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

The European Union Flippase Network

The Biochemical Society (UK)

The Australian Biochemical and Molecular Biology Society

Entry last updated: Saturday, 13 Feb 2010