International Protease Network

Department of Biochemistry & Molecular Biology
Monash University
Clayton, Vic 3800
Email: rob.pike@med.monash.edu.au
Tel: +61-3-9905 3923
Fax: +61-3-9905 4699
Homepage: http://www.med.monash.edu.au/biochem/staff/pike.html

Research

Our laboratory focuses on the proteases and related inhibitors and receptors that regulate the outcomes at the host-pathogen interface. To this end, we are actively investigating proteases of the human complement system and the inhibitors that regulate these enzymes. Our major activities surround the enzymes of the initiating complexes of the classical and lectin pathways of the complement system and the regulatory serpin, C1-inhibitor. We are investigating the interaction between the proteases and their substrates and their inhibitors. We are also interested in the proteases from pathogens that are involved in the pathogenesis of diseases. Our major interest in this regard is the proteases of the bacterium, Porphyromonas gingivalis, which causes periodontal disease. We are investigating the structure and function of these proteases and their interaction with host molecules to cause disease. Finally, we are interested in understanding how proteases interact with their substrates. To this end we are involved in efforts aimed at being able to use bioinformatic methods to predict novel substrates for proteases. This is a challenging area, but progress towards this ultimate aim is being made.

Collaborations

James Whisstock, Monash University, Australia
Phil Bird, Monash University, Australia
Steve Bottomley, Monash University, Australia
Jan Potempa, Jagiellonian University, Poland
Theresa Coetzer, University of Kwa-Zulu-Natal, South Africa
David Kemp, Queensland Institute for Medical Research, Australia
Eric Reynolds, University of Melbourne, Australia
Anna Blom, Lund University, Sweden
Eleanor Mackie, University of Melbourne, Australia
Klaudia Brix, Jacobs University Bremen, Germany

Publications

Ong PC, McGowan S, Pearce MC, Irving JA, Kan W-T, Grigoryev SA, Turk B, Silverman GA, Brix K, Bottomley SP, Whisstock JC & Pike RN. (2007) DNA accelerates the inhibition of human cathepsin V by serpins. Journal of Biological Chemistry 282, 36980-36986.

Kerr FK, O’Brien G, Quinsey NS, Whisstock JC, Boyd S, Garcia de la Banda M, Kaiserman D, Matthews AY, Bird PI & Pike RN. (2005) Elucidation of the substrate specificity of the C1s protease of the classical complement pathway. Journal of Biological Chemistry 280, 39510-39514.

Kerr FK, Thomas AR, Wijeyewickrema LC, Whisstock JC, Boyd SE, Kaiserman D, Matthews AY, Bird PI, Thielens NM, Rossi V & Pike RN. (2007) Elucidation of the substrate specificity of the MASP-2 protease of the lectin complement pathway and identification of the enzyme as a major physiological target of the serpin, C1-inhibitor. Molecular Immunology 45, 670-677.

Beckham SA, Piedrafita D, Phillips CI, Samarawickrema N, Law RHP, Smooker PM, Quinsey NS, Irving JA, Greenwood D, Verhelst SHL, Bogyo M, Turk B, Coetzer TH, Wijeyewickrema LC, Spithill TW & Pike RN. (2009) A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical active site features and a potential role in the digestive tract of newly excysted juvenile parasites. International Journal of Biochemistry and Cell Biology 41, 1601-1612.

Duncan RC, Wijeyewickrema LC & Pike RN. (2008) The initiating proteases of complement: controlling the cleavage. Biochimie 90, 387-395.

Potempa J & Pike RN. (2009) Corruption of innate immunity by bacterial proteases. Journal of Innate Immunity 1, 70-87.

Ng NM, Pike RN & Boyd SE. (2009) Subsite Cooperativity in Protease Specificity. Biological Chemistry 390, 401-407.

Fitzpatrick RE, Wijeyewickrema LC & Pike RN. (2009) The gingipains: scissors and glue of the periodontal pathogen, Porphyromonas gingivalis. Future Microbiology 4, 471-487.

Bergström FC, Reynolds S, Johnstone M, Pike RN, Buckle AM, Kemp DJ, Fischer K & Blom AM. (2009) Scabies mite inactivated serine protease paralogues inhibit the human complement system. Journal of Immunology 182, 7809-7817.

Boyd SE, Pike RN, M., Rudy GB, Whisstock JC & Garcia de la Banda M. PoPS: A Computational Tool for Modelling and Predicting Protease Specificity. (2005) Journal of Bioinformatics and Computational Biology 3, 551-585.