Faculty of Medicine, Dentistry and Health Sciences Department of Microbiology and Immunology

Purcell Laboratory

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Include: Research Interests | Major Research Projects | Laboratory Staff | Recent Publications

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Dr. Damian Purcell's Home Page

Research Interests

The Molecular Virology Laboratory primarily conducts research into the processing of viral messenger RNA (mRNA), with a specialized focus on the human immunodeficiency virus type 1 (HIV-1). The HIV-1 mRNA processing steps include splicing, polyadenylation, transport, cellular localisation, degradation and translation of mRNA into protein. Each step provides a potential means to modulate viral replication, infectivity and pathogenesis, therefore presenting likely targets for antiviral drug design. We study both the HIV-1 encoded and the host cell-derived control mechanisms that determine the efficiency of viral protein expression. RNA-dependent mechanisms, such as RNA interference (RNAi) support cellular antiviral defence pathways that are powerful innate mechanisms that restrict viral replication. We are investigating the convergence of these innate antiviral pathways with adaptive immunity.

From the perspective of virus, our studies of HIV-1 have shown that splicing generates a large array of alternatively spliced mRNAs from the nascent HIV-1 unspliced precursor-mRNA. Many of these mRNAs differ only in their 5' untranslated regions (UTR) and encode the same HIV-1 proteins. We have identified that env mRNAs use a ribosome shunting mechanism during translation, and our studies have identified mRNA elements that control this mechanism. Other aspects that determine translation control, such as the role of viral non-coding introns during viral replication, are also under investigation in our laboratory.

From the cellular aspect, we are focusing on the mechanisms that silence the expression of viral proteins in the astrocytes of brain. Astrocytes are important natural target cells for HIV-1 and their unusual refractory infection serves as a model that may yield novel approaches to restrict HIV-1 in other infected cell populations. Finally, we are applying our understanding of these fine details of HIV-1 and simian immunodeficiency virus (SIV) gene expression to the preparation of novel HIV-1 vaccines.

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Major Research Projects

  1. Mechanisms controlling translation of HIV-1 envelope protein
  2. Modulation of HIV gene expression by RNA binding proteins
  3. Modulation of HIV-1 RNA translation
  4. Regulation of mRNA splicing and stability in macrophages
  5. Control of HIV gene expression by siRNA
  6. Replicon based HIV vaccine development
  7. Vaccine for HIV neutralising antibodies
  8. Assays for HIV neutralising antibodies
  9. Immunomodulatory activities of HIV-1 Vpu protein

Laboratory Staff

Head and Senior Lecturer

Damian Purcell

Senior Research Officer and RD Wright Fellow (NHMRC)

Robert Center

Research Officer

Shahan Campbell

Senior Research Assistant

Jane Howard

Research Assistant

Carly Siebentritt

PhD Students

Marina Alexander
Helen Christensen
Sean Chung
Adam Johnson
Kate Lucas
Chi Ong
Adam Wheatley

MSc Student

Michael Braude

Honours Students 2007

Jasmine Tan
Jessica Waters

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Recent Publications - 2007/8

List of Publications prior to 2007

  1. Harrison DN, Gazina EV, Purcell DF, Anderson DA, Petrou S. Amiloride derivatives inhibit coxsackievirus B3 RNA replication. J Virol 2008;82: 1465-73.
  2. Lewin S R, Murray JM, Solomon A, Wightman F, Cameron PU, Purcell DF, Zaunders JJ, Grey P, Bloch M, Smith D, Cooper DA, Kelleher AD. Virologic determinants of success after structured treatment interruptions of antiretrovirals in acute HIV-1 infection. J Acquir Immune Defic Syndr 2008;47: 140-47.
  3. Dowling D, Nasr-Esfahani S, Tan CH, O'Brien K, Howard JL, Jans DA, Purcell DF, Stoltzfus CM, Sonza S. HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages. Retrovirology 2008;5: 18.
  4. Sterjovski J, Churchill MJ, Ellett A, Gray LR, Roche MJ, Dunfee RL, Purcell DF, Saksena N, Wang B, Sonza S, Wesselingh SL, Karlsson I, Fenyo EM, Gabuzda D, Cunningham AL, Gorry PR. Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with AIDS. Retrovirology 2007;4: 89.
  5. Sinck L, Richer D, Howard J, Alexander M, Purcell DF, Marquet R, Paillart JC. In vitro dimerization of human immunodeficiency virus type 1 (HIV-1) spliced RNAs. RNA 2007;13: 2141-50.
  6. Rollman E, Smith MZ, Brooks A, Purcell DFJ, Zuber B, Ramshaw IA, Kent SJ. Killing kinetics of SIV-specific CD8+ T cells: implications for HIV vaccine strategies. J Immunol 2007;179: 4571-4579.
  7. Huynh D, Vincan E, Mantamadiotis T, Purcell D, Chan CK, Ramsay R. Oncogenic properties of HIV-Tat in colorectal cancer cells. Curr HIV Res 2007;5: 403-9.
  8. Christensen HS, Daher A, Soye KJ, Frankel LB, Alexander MR, Laine S, Bannwarth S, Ong CL, Chung SW, Campbell SM, Purcell DF, Gatignol A. Small interfering RNAs against the TAR RNA binding protein, TRBP, a Dicer cofactor, inhibit human immunodeficiency virus type 1 long terminal repeat expression and viral production. J Virol 2007; 81(10): 5121-5131.
  9. Krummheuer J, Johnson AT, Hauber I, Kammler S, Anderson JL, Hauber J, Purcell DF, Schaal H. A minimal uORF within the HIV-1 vpu leader allows efficient translation initiation at the downstream env AUG. Virology 2007; 363(2): 261-271.
  10. Anderson JL, Johnson AT, Howard JL, Purcell DF. Both linear and discontinuous ribosome scanning are used for translation initiation from bicistronic human immunodeficiency virus type 1 env mRNAs. J Virol 2007; 81(9): 4664-4676.
  11. Cameron PU, Handley AJ, Baylis DC, Solomon AE, Bernard N, Purcell DF, Lewin SR. Preferential infection of dendritic cells during human immunodeficiency virus type 1 infection of blood leukocytes. J Virol 2007; 81(5): 2297-2306.

 

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