Griffith University

BSc (Hons), PhD

Senior Lecturer

Contact details for Dr Alan Munn

Research expertise

• Intracellular lipid and membrane protein trafficking processes and how these are exploited by viruses
• The role of the actin cytoskeleton in signal transduction pathways that control cell proliferation and cell migration
• Pathogenic fungi and their potential role in spread of papilloma virus infection

Current teaching areas

• Metabolism

Memberships

• Queensland State Representative, Australian Society of Biochemistry and Molecular Biology
• Member,Editorial Board, Australian Biochemist
  

Current Projects

Project 1. Host-encoded proteins critical for infection by enveloped viruses

The host protein known as Vps4 plays an essential role in the budding (release) of enveloped viruses from infected host cells during infection. Viruses that depend on Vps4 for budding include the Human Immunodeficiency Virus (HIV), Ebola Virus (EBOV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Herpes Simplex Virus (HSV). Vps4 is a cytoplasmic protein with ATPase activity that appears to act as an ATP-powered protein dissociation machine for a set of macromolecular complexes involved in membrane traffic. The 3D crystal structure of the Vps4 monomer has been elucidated. We and other research teams have solved a low-resolution structure of the Vps4 oligomer by electron microscopy and single particle analysis. The oligomer comprises two stacked hexameric rings. Recent work funded by the US Department of Defence has shown that one can down-regulate Vps4 in a living mouse and thereby protect the mouse from an otherwise lethal dose of Ebola virus without any adverse effects on the mouse. Hence, Vps4 may be an ideal target for antiviral compounds active against HIV, EBOV, HBV, HCV, HSV, etc. We have identified structural elements unique to Vps4 that are critical for in vivo Vps4 oligomer assembly and ATPase catalytic activity. We have also identified a number of other host proteins that interact with and function with Vps4. This project aims to screen for Vps4 inhibitory compounds and to explore the role of specific protein-protein interactions in Vps4 function in membrane traffic and enveloped virus budding. Our protocols do not require the use of animals or live viruses.

Project 2. The role of prion-like switches of protein conformation in health and disease

PCH (Pombe Cdc15 Homology) proteins have recently emerged as a major family of intracellular signalling proteins implicated in a wide range of human diseases including cancer, cardiovascular disease, diabetes, inflammatory disease, and neurodegeneration. Each PCH protein contains an alpha-helical domain known as an F-BAR domain that directly binds sheets of lipid bilayer membranes and converts them into fine tubules. Most PCH proteins also have a Src Homology 3 (SH3) domain that binds proline-rich motifs in other signalling proteins. We have shown that the SH3 domain of one PCH protein can switch from a normal state to a pathological state depending on the availability of a binding partner. In the pathological state the SH3 domain prevents cell division, blocks the uptake of material from the cell surface by endocytosis, and inhibits the assembly of actin monomers into actin filaments. This project aims to understand the biochemical basis for the switch of the SH3 domain from a normal to a pathological state. This pathological state is reminiscent of prions - cellular proteins of a switched 3D conformation that have the ability to actively switch all other molecules of the same protein into the pathological state. The switch in 3D protein conformation is stably inherited and constitutes a form of "protein-only inheritance" similar in effect to, but distinct from, mutation of DNA. The contribution of stably switched 3D protein conformation to human diseases such as cancer, diabetes, cardiovascular disease, and neurodegeneration could potentially be significant, but remains to be explored.

Publications

• JONES, K.L., MUNN, A.L., MAK, J. (2010) Proteins, nucleic acids, and lipids: a coordinated effort for the production of infectious virions during HIV assembly, In “Viral transport, assembly and egress” DIEFENBACH, R.J., CUNNINGHAM, A.L. (Eds.) Research Signpost/Transworld Research Network, Kerala, India [reviewed, revised and resubmitted, and currently awaiting editorial decision].
• MUNN, AL, ASPENSTRÖM, P. (2010). Second international conference on F-BAR proteins: October 1-3, 2009 at Rånäs Slott, Sweden. Cell Adh Migr. 4(1):81-93.
• MUNN, A.L., SATTLEGGER, E. (2009) Yeast studies reveal new roles for an ancient skeleton. Australian Biochemist, 40, 9-13.
• MUNN, A.L. (2009) Excellence and breadth: the success of cytoskeleton research in Australia and New Zealand, Australian Biochemist, 40, 3.
• MUNN, A.L., THANABALU, T.  (2009) Verprolin: a cool set of actin-binding sites and some very HOT prolines. IUBMB Life, 61, 707-12.
• MUNN, A.L., WINSOR, B.A.T. (2009) The budding yeast PCH/F-BAR proteins, In “The pombe Cdc15 homology proteins”, ASPENSTRÖM, P. (Ed.), Landes Bioscience, Austin, Texas, USA.
• *LANDSBERG, M.J., VAJJHALA, P.R., ROTHNAGEL, R., MUNN, A.L., HANKAMER, B. (2009) Three-dimensional structure of AAA ATPase Vps4: advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding. Structure, 17, 427-37. [*listed in Faculty of 1000 Biology as one of the world’s most important research articles in the field of biology as judged by an international panel comprising 2000 eminent biologists].
• RAJMOHAN, R., WONG, M.H., MENG, L., MUNN, A.L., THANABALU, T.  (2009) Las17p-Vrp1p but not Las17p-Arp2/3 interaction is important for actin patch polarization in yeast. Biochim Biophys Acta, 1793, 825-35.
• STEPHENS, A.E., GARDINER, D.M., WHITE, R.G., MUNN, A.L., MANNERS, J.M. (2008) Phases of infection and gene expression of Fusarium graminearum during crown rot disease of wheat. Mol Plant Microbe Interact, 21, 1571-81.
• DESMOND, O.J., MANNERS, J.M., STEPHENS, A.E., MACLEAN, D.J., SCHENK, P.M., GARDINER, D.M., MUNN, A.L., KAZAN, K. (2008) The Fusarium mycotoxin deoxynivalenol elicits hydrogen peroxide production, programmed cell death and defence responses in wheat. Mol Plant Pathol, 9, 435-45.
• VAJJHALA, P.R., NGUYEN, C.H., LANDSBERG, M.J., KISTLER, C., GAN, A.L., KING, G.F., HANKAMER, B., MUNN, A.L. (2008) The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPases. FEBS J, 275, 1427-49.
• VAJJHALA, P.R., MUNN, A.L. (2007) Host factors in virus budding – insights from yeast. Microbiology Australia, 28, 59-61.
• THANABALU, T., RAJMOHAN, R., MENG, L., REN, G., VAJJHALA, P.R., MUNN, A.L. (2007) Verprolin function in endocytosis and actin organization. Roles of the Las17p (yeast WASP)-binding domain and a novel C-terminal actin-binding domain. FEBS J, 274, 4103-25.
• VAJJHALA, P.R., CATCHPOOLE, E., NGUYEN, C.H., KISTLER, C., MUNN, A.L. (2007) Vps4 regulates a subset of protein interactions at the multivesicular endosome. FEBS J, 274,1894-907.
• WIRADJAJA, F., OOMS, L.M., TAHIROVIC, S., KUHNE, E., DEVENISH, R.J., MUNN, A.L., PIPER, R.C., MAYINGER, P., MITCHELL, C.A. (2007) Inactivation of the phosphoinositide phosphatases Sac1p and Inp54p leads to accumulation of phosphatidylinositol 4,5-bisphosphate on vacuole membranes and vacuolar fusion defects. J Biol Chem, 282,16295-307.
• VAJJHALA, P.R., WONG, J.S., TO, H.Y., MUNN, A.L. (2006) The beta domain is required for Vps4p oligomerization into a functionally active ATPase. FEBS J, 273,2357-73.
• REN G., VAJJHALA, P., LEE, J.S., WINSOR, B., MUNN, A.L. (2006) The BAR domain proteins: molding membranes in fission, fusion, and phagy. Microbiol Mol Biol Rev, 70, 37-120.
• *BRINKWORTH, R.I., MUNN, A.L., KOBE, B. (2006) Protein kinases associated with the yeast phosphoproteome. BMC Bioinformatics, 7, 47. [*listed in Faculty of 1000 Biology as one of the world’s most important research articles in the field of biology as judged by an international panel comprising 2000 eminent biologists]
• WANG, P., DUAN, W., MUNN, A.L., YANG, H. (2005) Molecular characterization of Osh6p, an oxysterol binding protein homolog in the yeast Saccharomyces cerevisiae. FEBS J, 272, 4703-15.
• WANG, P., ZHANG, Y., LI, H., CHIEU, H.K., MUNN, A.L., YANG, H. (2005) AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism. EMBO J, 24, 2989-99.
• REN, G., WANG, J., BRINKWORTH, R., WINSOR, B., KOBE, B., MUNN, A.L. (2005) Verprolin cytokinesis function mediated by the Hof one trap domain. Traffic, 6, 575-93.

Recently Funded Grants

• Griffith University Research Infrastructure Programme, Automated electrophysiology for studies on ion channels and receptors to enhance research capability in neurobiology, cardiovascular sciences and drug discovery, CIs: S. Nirthanan, R. Rose’Meyer, J. Lewohl, A. Munn, S. Dukie, G. Grant, Funds awarded: 2011, $100,000, Source: Griffith University.
• DP110100389, A role for the actin cytoskeleton in suppression of prion pathology in yeast, Dr Alan L. Munn (CIA), Assoc Prof Ming Q. Wei (CIB), Prof Yury Chernoff (CIC), Assoc Prof Mingjie Cai (CID), Funding awarded: 2011, $80,000; 2012, $75,000; 2013, $80,000; Total $235,000. Funding source: Australian Research Council (Australian Federal Government).
• LEWOHL, J., COLSON, N., NIRTHANAN, N., MUNN, A.L., NAUG, H., ROSE’MEYER, R. 2010, $95,000, GURIP, Griffith University.
• MUNN, A.L. (CIA), MAK, J., LEWIN, S., 2008-2009, $140,381, Australian Centre for HIV and Hepatitis Virology Research (ACH2) EoI, Griffith University.
• MEUNIER, F., STOW, J.L., PARTON, R.G., NOAKES, P., COULSON, E., MUNN, A.L., HOOPER, J.D., 2008, $260,000, ARC LIEF (LE0882864), University of Queensland.
• KOBE, B., SMITH, R., McEWAN, A.G., YOUNG, P.R., MUNN, A.L., KROMYKH, A.A., BROWN, M.A., ROTHNAGEL, J.A., SCHEMBRI, M.A., GRAY, P.P., NIELSEN, L.K., GUDDAT, L.W., KAPPLER, U., FRASER, J.A., KELLIE, S., MAHLER, S.M., 2007, $30,000, NHMRC Equipment grant, University of Queensland.
• KOBE, B., SMITH, R., McEWAN, A.G., YOUNG, P.R., MUNN, A.L., KROMYKH, A.A., BROWN, M.A., ROTHNAGEL, J.A., SCHEMBRI, M.A., GRAY, P.P., NIELSEN, L.K., GUDDAT, L.W., KAPPLER, U., FRASER, J.A., KELLIE, S., MAHLER, S.M., 2007, $195,000, RIBG, University of Queensland.
• MUNN, A.L., 2007, $13,619, ResTeach Fellowship (10%), University of Queensland.
• KUMAR, S., MUNN, A.L. (CIB), 2004-2006, $480,750, NHMRC Project, University of Adelaide.
• MUNN, A.L., 2004, $12,000, UQ New Staff Research Start-Up Grant, University of Queensland.
• MUNN, A.L., 2003-2005, $210,000, NHMRC Project, University of Queensland.