Melbourne Dental School

Dr. Neil O’Brien-Simpson

CONTACT

E-mail: neil.obs@unimelb.edu.au

Telephone: +61 3 9341 1550

QUALIFICATIONS AND POSITION

SHORT HISTORY

Neil O’Brien-Simpson has an interdisciplinary background, combining organic and peptide chemistry with immunology to develop novel vaccines and therapeutics and investigating the immune response to pathogens. He was originally trained in biological sciences and management at Napier University (Edinburgh, Scotland) and worked at I.C.I Chemicals and Polymers Division (Grangemouth and Runcorn) as a research organic chemist. In 1993 he was awarded an Overseas postgraduate research scholarship and a CRC for vaccine technology scholarship to study for his Ph.D at The University of Melbourne, Department of Microbiology and Immunology. During his Ph.D he was trained in peptide chemistry and immunology and developed in his thesis a method of producing a multi-valent peptide vaccine, which resulted in several publications and a patent. After being awarded his Ph.D he went to the School of Dental Science, The University of Melbourne, to do postdoctoral research with Eric Reynolds on the development of a vaccine against the bacterium Porphyromonas gingivalis a causative agent of periodontitis. His work in this area has resulted in a further 5 patents, numerous publications and government support in the form of grants from both national and international agencies. Further his research into vaccine design and periodontitis has resulted in Neil being awarded: the Colgate Prize for Dental Research (1999), The IADR Hatton Award (2000) and the Oral Biology Award (2003). In 2003 he was awarded a CR Roper Fellowship and in 2004 he became program co-leader for the Novel Diagnostics, Vaccines and Pharmaceuticals Research Program in the newly formed Co-operative Research Centre for Oral Health Science.

He is currently engaged in several research programs, notably in design, development and delivery of sub-unit vaccines, understanding and developing models of the immune response to bacterial infection and in the synthesis of structured and phosphorylated peptides.

RESEARCH INTERESTS

CURRENT RESEARCH PROJECTS

(Projects that are available (1) for AMS; (2) for BSc Hons; (3) for Masters by Research; (4) for PhD; students are indicated by a superscript number).

RESEARCH LABORATORY FACILITIES

Neil’s research is conducted within a large highly integrated research group which allows direct access to the instrumentation located within this group. This research group consists of several well-equipped multidisciplinary laboratories including: Immunology (flow cytometry/cell sorting lab, tissue culture lab, cell harvesting/analysis lab), Microbiology (continuous culture lab, confocal microscopy lab), Molecular Biology (micro-array lab, real-time PCR lab, liquid handling/robitics lab) Proteomics (MALDI TOF/TOF lab, Nano LC-ion spray [ion trap] lab, 2D electrophoresis/robitics labs), Structure lab (computer modeling lab), Peptide/protein lab (consiting of HPLC’s, CE’s, BIACORE 3000, peptide synthesizers), Biomineralisation lab, Radiolab and a Computer and Imaging Lab. The laboratories are regarded as the premier oral research laboratories in Australia and are extensively equipped with state-of-the-art equipment.

CURRENT PUBLICATIONS

PATENTS

  1. Polymers Incorporating Peptides – Jackson, D.C, O’Brien-Simpson, N.M. Brown, L.E. Ede, N.J. Brandt, E. Zheng, W (1997).
  2. Synthetic Peptide Constructs for Diagnosis and Treatment of Periodontitis Associated with Porphyromonas gingivalis – Reynolds EC, O’Brien-Simpson NM, Slakeski N. (1998).
  3. Antimicrobial Peptides – Reynolds EC, Dashper SG, Malkoski M, O’Brien-Simpson NM, Talbo G, Cross KJ (1999).
  4. Synthetic Peptides Containing Protective Epitopes for the Treatment and Prevention of Periodontitis Associated with Porphyromonas gingivalis – Reynolds EC, O’Brien-Simpson NM. (2001).
  5. Porphyromonas gingivalis Antigenic Composition– Reynolds EC, O’Brien-Simpson NM. (2002).
  6. Vaccine – Cheers, C, McKenzie,IFC, Pietersz, GA, Stambas, J, Reynolds EC, O’Brien-Simpson NM. (2003).

RECENT PUBLICATIONS

  1. O’Brien-Simpson, N.M, Veith, P.D, Dashper, S.G, Reynolds, E.C. “Antigens of bacteria associated with periodontitis.” Periodontology 2000. 35 1-34 (2004). Invited Review.
  2. O’Brien-Simpson, N.M, Veith, P.D, Dashper, S.G, Reynolds, E.C. “Porphyromonas gingivalis gingipains: The molecular teeth of a microbial vampire” Current Protein and Peptide Science 4 (6) 409-426 (2003). Invited Review
  3. Rajapakse P.S, O’Brien-Simpson N.M, Slakeski N, Hoffmann B, Reynolds E.C. “Immunization with the RgpA-Kgp proteinase-adhesin complexes of P. gingivalis protects against periodontal bone loss in the rat periodontitis model. Infection and Immunity 70 (5) 2480-2486 (2002).
  4. O’Brien-Simpson N.M, Paolini R.A, Hoffmann B, Slakeski N, Dashper S.G, Reynolds E.C. “Role of RgpA, RgpB and Kgp proteinases in virulence of Porphyromonas gingivalis in the murine lesion model.” Infection and Immunity 69 (12) 7527-7534 (2001).
  5. Malkoski M, Dashper S.G, O’Brien-Simpson N.M, Talbo G, Macris M, Cross K.J, Reynolds E.C “A novel antibacterial peptide from bovine milk, Kapacin, Ser(P)149 κ-Casein (106-169)” Journal of Antimicrobial and Chemotherapeutic Agents 45 (8) 2309-2315 (2001).
  6. O’Brien-Simpson N.M, Black C.L, Bhogal P.S, Cleal S.M, Slakeski N, Higgins T.J, Reynolds E.C. “Serum IgG and IgG subclass responses to the PrtR-PrtK proteinase-adhesin complex of Porphyromonas gingivalis in adult periodontitis” Infection and Immunity 68(5) 2704-2712 (2000).
  7. Reynolds E.C, O’Brien-Simpson N.M. “Cardiovascular disease and periodontal disease: microbial direct toxic effects on endothelial cells.” Periodontology. 21(1) 24-31 (2000).
  8. O’Brien-Simpson N.M, Paolini R.A, Reynolds E.C. “RgpA-Kgp peptide-based immunogens provide protection against Porphyromonas gingivalis challenge in a murine lesion model.” Infection and Immunity 68 4055-4063 (2000).
  9. O’Brien-Simpson N.M, Dashper S.G, Reynolds E.C. “Histatin 5 is a substrate and not an inhibitor of the Arg- and Lys-specific proteinases of Porphyromonas gingivalis.” Biochemical and Biophysical Research Communications 250: 474-478 (1998).
  10. Slakeski N, Bhogal P.S, O’Brien-Simpson N.M, Reynolds E.C. “Characterisation of a second cell-associated Arg-specific cysteine proteinase of Porphyromonas gingivalis and identification of an adhesin binding motif involved in association of the prtR and prtK proteinases and adhesins into large complexes.” Microbiology 144: 1583-1592 (1998).
  11. Dashper SG, O’Brien-Simpson NM, Bhogal PS, Franzmann AD, Reynolds EC. “Purification and characterization of a putative fimbrial protein/receptor of Porphyromonas gingivalis.” Australian Dental Journal. 43:99-104 (1998).
  12. Jackson, D.C, O’Brien-Simpson, N.M. Ede, N.J. Brown, L.E. “Free radical induced olymerization of synthetic peptides into polymeric immunogens.” Vaccine, 1997, 15(15) 1697-1705.
  13. O’Brien-Simpson, N.M. Ede, N.J. Brown, L.E. Swan, J. Jackson, D.C. “Polymerisation of unprotected synthetic peptides: A view toward synthetic peptide vaccines.” Journal of the American Chemical Society. 1997, 119(6), 1183-1188.

CONFERENCE PAPERS

  1. O’Brien-Simpson, N.M. Ede, N.J. Brown, L.E. Swan, J. Jackson, D.C. “Polymerisation of unprotected synthetic peptides” 2nd Australian Peptide Conference October 6-11. 1996
  2. O’Brien-Simpson, N.M, Paolini R, Reynolds EC. “Peptide-based immunogens provide protection against Porphyromonas gingivalis challenge in a murine abscess model” 3rd Australian Peptide Conference October 4-9 1998
  3. O’Brien-Simpson, N.M, Paolini R, Reynolds EC. “Synthetic peptides from the proteinase-adhesin complex of Porphyromonas gingivalis provide protection in a murine abscess model” International Union of Microbiological Societies Congress. August 16-20, 1999.
  4. O’Brien-Simpson, N.M, Paolini R, Reynolds EC “Synthetic peptide immunogens protect against Porphyromonas gingivalis challenge in a murine abscess model” International Association for Dental Research ANZ Division Conference September 27-29, 1999
  5. O’Brien-Simpson, N.M, Paolini R, Reynolds EC “Synthetic peptide immunogens protect against Porphyromonas gingivalis challenge in a murine abscess model” International and American Associations for Dental Research Conference April 5-8, 2000. Washington D.C.
  6. O’Brien-Simpson, N.M, Paolini R, Pathirana R, Chen Y-Y, Reynolds EC “The adhesins and not the proteinases of the RgpA-Kgp proteinase-adhesin complex are immunodominant and provide protection in the murine periodontitis and abscess models” Gordon Research Conference on Periodontal Disease. July 16-21, 2000. Oxford, UK.
  7. O’Brien-Simpson, N.M, Lam, R.S.S, Reynolds EC “Role of macrophages in the murine periodontitis model” Society for Cytokines, Inflammation and Leukocytes Conference. February 1-3, 2002. Lorne, Australia.
  8. O’Brien-Simpson, N.M, Reynolds EC “Periodontitis, a chronic inflammatory disease of the tooth’s supporting tissues” Society for Cytokines, Inflammation and Leukocytes Conference. February 1-3, 2002. Lorne, Australia.
  9. O’Brien-Simpson, N.M, Lam, R.S.S, Reynolds EC “Role of macrophages in Porphyromonas gingivalis-induced bone loss in a murine periodontitis model” Australasian Society for Immunology. December 8-12, 2002. Brisbane, Australia.
  10. O’Brien-Simpson NM, Reynolds EC. “Synthetic peptides protect against P. gingivalis induced bone loss” IADR-ANZ divisional Meeting Melbourne September 2003.
  11. Dashper SG, Butler C, Lissel P, Snelgrove S, Paolini R, Slakeski N, O’Brien-Simpson N & Reynolds E. Iron acquisition and virulence of Porphyromonas gingivalis. Bacterial Pathogenesis Conference, Aust. Society for Microbiology. May 2003.
  12. Attard TJ, O’Brien-Simpson NM, Huq NL, Cross KJ, Reynolds EC. “Calcium binding of phosphopeptides” IADR-ANZ divisional Meeting Melbourne September 2003.
  13. Orth RKH, Dashper SG, O’Brien-Simpson NM, Reynolds EC. “Growth and enumeration of the periodontopathogen Treponema denticola in a novel media” IADR-ANZ divisional Meeting Melbourne September 2003.
  14. Taylor L, Slakeski N, Paolini R, O’Brien-Simpson NM, Reynolds EC. “Expression of a recombinant Porphyromonas gingivalis adhesin, Kgp39, and analysis of its immunogenicity using the murine lesion model” IADR-ANZ divisional Meeting Melbourne September 2003.
  15. Lam RSS, O’Brien-Simpson NM, Reynolds EC. “ The role of macrophages in the murine periodontitis model” IADR-ANZ divisional Meeting Melbourne September 2003.
  16. Tam V, O’Brien-Simpson NM, Reynolds EC. “Murine T-cell epitope mapping of the RgpA-Kgp proteinase-adhesin complex of Porphyromonas gingivalis’ IADR-ANZ divisional Meeting Melbourne September 2003.
  17. Pathirana RD, O’Brien-Simpson NM, Visvanathan K, Hamilton JA,Reynolds EC. “Porphyromonas gingivalis W50 adherence to epithelial, fibroblast and endothelial cells” IADR-ANZ divisional Meeting Melbourne September 2003.

CURRENT GRANTS AS A CHIEF INVESTIGATOR

Current grants listed by agency name and title of project
Agency Short title
NIH Development of a defined Porphyromonas gingivalis vaccine
NIH Impact of oral interactions on periodontitis
NHMRC The RgpA-Kgp proteinase-adhesin complex and virulence of Porphyromonas gingivalis
NHMRC Anticariogenic casein phosphopeptide-amorphous calcium fluoride phosphate
NHMRC – Strategic Research Development grant Development of a site-specific, predictive assay for periodontal disease progression using mass spectrometric and real-time PCR analysis.”
NHMRC Polymicrobial pathogenesis in a murine periodontitis model.
NHMRC Molecular studies of dentine phosphoporyn and development of a biomimetic dental restorative material
AusIndustry, Department of Industry, Science and Resources Co-operative Research Center (CRC) for Oral Health Science
Science, Technology and Innovation Initiative Victorian Centre for Oral Health Science
ADRF Characterization of the RgpA-Kgp proteinase-adhesin complex of Porphyromonas gingivalis W50 in the murine periodontitis model

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