Professor Peter Colman

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Division: Structural Biology

Research Overview

The intrinsic pathway to cell death is controlled by the Bcl-2 family of proteins. High levels of these proteins can render cells resistant to chemotoxic insults. Such resistance is a hallmark of certain cancers. Some viruses express proteins which block the intrinsic cell death pathway by functioning as mimics of Bcl-2. Understanding the interactions of the Bcl-2 family proteins with their natural antagonists may inform the discovery of organic ligands capable of killing cells.

Research Interests

Selected Publications

    1. Czabotar PE, Lee EF, Thompson GV, Wardak AZ, Fairlie WD, Colman PM. Mutations to Bax beyond the BH3 domain disrupts interactions with pro-survival proteins and promotes apoptosis. J Biol Chem. 2011 Mar 4;286(9):7123-31. PMID: 21199865
    2. Czabotar PE, Westphal D, Dewson G, Ma S, Hockings C, Fairlie WD, Lee EF, Yao S, Robin AY, Smith BJ, Huang DC, Kluck RM, Adams JM, Colman PM. Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell. 2013 Jan 31;152(3):519-31. PMID: 23374347
    3. Lessene G, Czabotar PE, Sleebs BE, Zobel K, Lowes KN, Adams JM, Baell JB, Colman PM, Deshayes K, Fairbrother WJ, Flygare JA, Gibbons P, Kersten WJ, Kulasegaram S, Moss RM, Parisot JP, Smith BJ, Street IP, Yang H, Huang DC, Watson KG. Structure-guided design of a selective Bcl-xL inhibitor. Nat Chem Biol. 2013 Jun;9(6):390-7. PMID: 23603658
    4. Lessene G, Czabotar PE, Colman PM.  BCL-2 family antagonists for cancer therapy.  Nat Rev Drug Discov. 2008 Dec;7(12):989-1000 PMID: 19043450 [PubMed - indexed for MEDLINE]
    5. Kvansakul M, Yang H, Fairlie WD, Czabotar PE, Fischer SF, Perugini MA, Huang DC, Colman PM.  Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands.  Cell Death Differ. 2008 Oct;15(10):1564-71 PMID: 18551131 [PubMed - indexed for MEDLINE]
    6. Dewson G, Kratina T, Sim HW, Puthalakath H, Adams JM, Colman PM, Kluck RM.  To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3:groove interactions.  Mol Cell. 2008 May 9;30(3):369-80 PMID: 18471982 [PubMed - indexed for MEDLINE]
    7. Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle MJ, Willis SN, Puthalakath H, Bouillet P, Colman PM, Huang DC, Fairlie WD.  A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation.  J Cell Biol. 2008 Jan 28;180(2):341-55 PMID: 18209102 [PubMed - indexed for MEDLINE]
    8. Lee EF, Czabotar PE, Smith BJ, Deshayes K, Zobel K, Colman PM, Fairlie WD.  Crystal structure of ABT-737 complexed with Bcl-xL: implications for selectivity of antagonists of the Bcl-2 family.
      Cell Death Differ. 2007 Sep;14(9):1711-3 PMID: 17572662 [PubMed - indexed for MEDLINE]
    9. Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM.  Structural insights into the degradation of Mcl-1 induced by BH3 domains.  Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22 PMID: 17389404 [PubMed - indexed for MEDLINE]
    10. Kvansakul M, van Delft MF, Lee EF, Gulbis JM, Fairlie WD, Huang DC, Colman PM.  A structural viral mimic of prosurvival Bcl-2: a pivotal role for sequestering proapoptotic Bax and Bak.  Mol Cell. 2007 Mar 23;25(6):933-42 PMID: 17386268 [PubMed - indexed for MEDLINE]

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    Current Laboratory Members

    Faculty Member: Peter Colman, BSc(Hons), PhD (Adelaide), FAA, FTSE

    Senior Postdoctoral Fellow: Yibin Xu, BSc China MSc China PhD ANU

    Postdoctoral Fellow: Adeline Robin, MSc Louis Pasteur, PhD Basel

    Research Assistant: Geoff Thompson, BSc(Hons) Melb

    Research Assistant: Ahmad Wardak, BSc(Hons) LaT

    PhD Student: Jason Brouwer, BBiomedSc(Hons) Monash

    Scientific coordinator: Amanda Voudouris, BSc Monash