Dr Doug Fairlie

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Division: Structural Biology

Research Overview

My laboratory is interested in the molecular mechanisms underlying the fundamental cellular process of apoptosis, or programmed cell death. We use a combination of biochemical, cell biology and structural biology techniques to dissect the Bcl-2 mediated apoptosis pathways to better understand how cell death is regulated at a molecular level, and to create new tools that will help in the development of drugs.

More recently, my laboratory has become interested in the Bcl-2 pathway in the parasite that causes schistosomiasis, a major disease in developing countries. We will use similar approaches to dissect the apoptosis pathways in schistosomes with the aim of providing insights into whether these proteins will make good drug targets.

 

Research Interests

  • Mechanisms of apoptosis in schistosomes
  • Structural biology of the Bcl-2 pathway in humans
  • Evolution of the mechanisms of apoptosis
  • Characterisation of non-natural peptides (foldamers)

Selected Publications

  1. Lee EF, Smith BJ, Horne WS, Mayer KN, Evangelista M, Colman PM, Gellman SH, Fairlie WD (2011) Structural basis of Bcl-x(L) recognition by a BH3-mimetic α/β-peptide generated by sequence-based design. Chembiochem doi: 10.1002/cbic.201100314. [Epub ahead of print] PMID: 21744457 [PubMed - as supplied by publisher] 
  2. Lee EF, Clarke OB, Evangelista M, Feng Z, Speed TP, Tchoubrieva EB, Strasser A, Kalinna BH, Colman PM, Fairlie WD (2011) Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes. Proc Natl Acad Sci USA Apr 26;108(17):6999-7003. Epub 2011 Mar 28. PMID: 21444803 [PubMed - indexed for MEDLINE]
  3. Hagen J, Lee EF, Fairlie WD, Kalinna BH (2011) Functional genomics approaches in parasitic helminths. Parasite Immunol Jun 29. doi: 10.1111/j.1365-3024.2011.01306.x. [Epub ahead of print] PMID: 21711361 [PubMed - as supplied by publisher]
  4. Lee EF, Czabotar PE, Yang H, Sleebs BE, Lessene G, Colman PM, Smith BJ and Fairlie WD (2009) Conformational changes in Bcl-2 pro-survival proteins determine their capacity to bind ligands. J Biol Chem 284:30508-30517. PMID: 19726685 [PubMed - indexed for MEDLINE]
  5. Lee EF, Fedorova A, Zobel K, Boyle MJ, Yang H, Perugini MA, Colman PM, Huang DCS, Deshayes K and Fairlie WD (2009) Novel Bcl-2 homology (BH)-3 domain-like sequences identified from screening large peptide libaries for inhibitors of the pro-survival Bcl-2 proteins. J Biol Chem 284:31315-31326. PMID: 19748896 [PubMed - indexed for MEDLINE]
  6. Lee EF, Sadowsky JD, Smith BJ, Czabotar PE, Peterson-Kaufman KJ, Colman PM, Gellman SH, and Fairlie WD (2009) High-resolution structural characterization of a helical α/β-peptide foldamer bound to the anti-apoptotic protein Bcl-xL Angew Chemie Intl Ed 48:4318-4322. PMID: 19229915 [PubMed - indexed for MEDLINE]
  7. Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle M, Willis SN, Puthalakath H, Bouillet P, Colman PM, Huang DCS and Fairlie WD (2008) A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation. J Cell Biol 180:341-355 PMID: 18209102 [PubMed - indexed for MEDLINE]
  8. Lee EF, Czabotar PE, Smith BJ, Deshayes K, Zobel K, Colman PM, Fairlie WD (2007) Crystal structure of ABT-737 complexed with Bcl-xL: Implications for selectivity of antagonists of the Bcl-2 family. Cell Death Differ 14:1711-1713 PMID: 17572662 [PubMed - indexed for MEDLINE]
  9. Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P, Strasser A, Kluck RM, Adams JM, Huang DC (2007) Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315: 856-859 PMID: 17289999 [PubMed - indexed for MEDLINE]
  10. Sadowsky JD, Fairlie WD, Hadley EB, Lee, HS, Umezawa N, Nikolovska-Coleska Z, Wang S, Huang DC, Tomita Y, Gellman SH. (2007) (alpha/beta+alpha)-peptide antagonists of BH3 domain/Bcl-xL recognition: Toward general strategies for foldamer-based inhibition of protein-protein interactions. J Am Chem Soc 129:139-154 PMID: 17199293 [PubMed - indexed for MEDLINE]

Click here to view more PubMed publications

Current Laboratory Members

Faculty member: Douglas Fairlie BSc(Hons) PhD Monash

Postdoctoral fellow: Erinna Lee BSc(Hons) PhD Melb

Research assistant: Marco Evangelista: BBiotech(Hons) Adelaide

UROP student: Grace Gold, University of Melbourne

 

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