Dr. Megan O'Mara
I'm interested in the way transmembrane proteins function as molecular motors. Like a physical motor, molecular motors move through a series of different states during their power cycle. For example, transmembrane proteins such as ion channels and active transporters allow the transport or diffusion of compounds across the cell membrane in a highly controlled manner. Conformational changes in ion channels provide a tightly regulated passive diffusion of ions down their concentration gradient. This is the underlying basis of nerve conduction and many other physiological processes. In active transporters such ATP transporters, translocation of substrate across the membrane is powered by large scale conformational changes in the protein arising from the hydrolysis of its fuel, ATP, to ADP. ATP transporters are a medically important class of proteins. For example, the human multi-drug ABC transporter, P-glycoprotein protects us from toxic compounds we ingest. However, when a cancer patient is treated with chemotherapy, production of P-glycoprotein is upregulated, often leading to chemotherapy resistant cancer strains. While these examples give highly specific transport of a given substrate, transmembrane proteins such as viral fusion proteins are anchored in the viral membrane, then attach to the host membrane and undergo conformational changes which bring about fusion of the viral and host cell membranes, allowing infiltration and replication of a virus. This mechanism is particularly important in viruses such as Dengue Fever, HIV and Ebola.
Research grants, awards and professional activities
- University of Queensland Post-doctoral Fellowship. Commenced in January 2009.
- Canadian Institute of Health Research (CIHR) Post-doctoral Fellowship. November 2005 - December 2008.
- Robert and Helen Crompton International Travel Scholarship 2005.
- Director’s Prize, John Carver Post-graduate Seminars (ANU), September 2002.
- Australian Institute of Physics Award for Post-graduate Excellence, 2002.
- ACT student representative for the Australian Institute of Physics. 2003 and 2004.
- Australian Institute of Physics student representative to Science Meets Parliament. 2003.
- Student representative to the Faculty Board of the Research School of Physical Sciences and Engineering, 2003
- Member of the Biophyscial Scociety
- Member of the Australian Society for Biophysics
- Member of the Australian Institute of Physics
Publications in refereed journals
- P.M. Jones, M.L. O'Mara, A.M. George. 2009. ABC transporters: a riddle wrapped in a mystery inside an enigma. TIBS, accepted for publication.
- Crowley, E., M.L. O'Mara, C. Reynolds, D.P. Tieleman, J. Storm, I.D. Kerr, R. Callaghan. 2009. Transmembrane Helix 12 Modulate Progression of the ATP Catalytic Cycle in ABCB1. Biochemistry. In press.
- Oancea, G., M.L. O’Mara, W.F.D. Bennett, D.P. Tieleman, R. Abele and R. Tampé. 2009. Structural Arrangement of the Transmission Interface in the ABC Transporter TAP Critical for Antigen Binding and Translocation. PNAS 106:5551-5556.
- E. Procko, M.L. O’Mara, W.F.D. Bennett, D.P. Tieleman and R. Gaudet. 2009. The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter. FASEB J 23: 1287-1302.
- Klassen, T.L. M.L. O'Mara, M. Redstone, A.N. Spencer, W.J. Gallin. 2008. Intramolecular interactions that determine voltage-sensitivity in a cnidarian voltage-gated potassium channel, jShak1. J Exp Biol. 211:3442-3453.
- Moussatova, A., C. Kandt, M.L. O’Mara, D.P. Tieleman. 2008. ATP binding cassette transporters in Escherichia coli. BBA, 1778:1757-1771.
- Storm, J., S. Modok, M.L. O’Mara, D.P. Tieleman, I.D. Kerr, R. Callaghan. 2008. The cytosolic region of TM6 in P-glycoprotein: topographical analysis and functional perturbation by site directed labelling. Biochemistry, 47:3615-3624.
- Lawson, J., M.L. O'Mara, I.D. Kerr. 2007. Structure-based interpretation of the mutagenesis database for the nucleotide binding domains of P-glycoprotein. BBA Biomembranes, 1778: 376-391.
- O’Mara, M.L. and D.P. Tieleman. 2007. P-glycoprotein models of apo and ATP-bound states based on homology with Sav1866 and MalK. FEBS Letters, 581:4217-4222.
- Storm, J., M.L. O’Mara, E. Crowley, J. Peall, D.P. Tieleman, I.D. Kerr and R. Callaghan. 2007. Residue G346C in the transmembrane segment six is involved in inter-domain communication in P-glycoprotein. Biochemistry 46:9899-9910.
- O’Mara, M.L., A. Oakley and S. Broer. 2006. Mechanism and putative structure of B0-like neutral amino acid transporters. J. Membrane Biology 213(2):111-118.
- Oloo, E., C. Kandt, M.L. O’Mara and D.P. Tieleman. 2006. Computer simulations of ABC transporter components. Biochem Cell Biol 84(6):900-911.
- O'Mara, M.L., B.A. Cromer, M.W. Parker and S.H. Chung. 2005. Homology Model of the GABAA Receptor Examined Using Brownian Dynamics. Biophys J. 88: 3286-3299.
- Corry, B, M. O’Mara and S.H. Chung. 2004. Permeation dynamics of chloride ions in the ClC-0 and ClC-1 channels, Chem Phys Letters 386:233-238.
- Corry, B, M. O’Mara and S.H. Chung, 2004. Conduction Mechanisms of Chloride Ions in ClC-type Channels. Biophys J. 86: 846-860.
- O’Mara, M., P.H. Barry and S.H. Chung. 2003. A model of the glycine receptor deduced from Brownian dynamics studies. PNAS 100: 4310-4315.
Abstracts, proceedings and conference presentations
- O'Mara, M.L. and D.P. Tieleman. Determining the structural conformation of P-glycoprotein via homology modelling. Biophysical Society Meeting Abstracts. Biophys. J., 564A-564A Suppl. S JAN 2007
- O'Mara, M.L., C. Kandt and D.P. Tieleman. Developing a structural model of P-glycoprotein. FEBS Special Meeting ATP-Binding Cassette (ABC) Proteins: From Multidrug Resistance to Genetic Diseases. 4-10 March, 2006. Abstract
- O'Mara, M.L., J. Yin, M. Hoyles and S.-H. Chung. Investigating the mechanism of proton transfer through the bacterial ClC transporter. Biophysical Society Meeting Abstracts. Biophys. J., Suppl. S Jan 2006. 2792-Pos.
- O’Mara, M.L., B.A. Cromer, M.W. Parker and S.H. Chung. Simulations of ion permeation through a homology model of the GABAA receptor. Biophys. J. 88(1):150A-150A Part 2 Suppl. S JAN 2005
- Barry P.H. and O’Mara M.L. The reliability of relative cation-anion permeabilities deduced from reversal (dilution) potential measurements in ion channel studies, and Brownian dynamics predictions. FASEB JOURNAL 19 (5): A1170-A1170 Part 2 Suppl. S MAR 7 2005
- Corry B, O'Mara M, Bisset D, S.H. Chung. Mechanisms of chloride conduction in ClC channels Biophys. J. 86 (1): 5A-5A Part 2 Suppl. S JAN 2004
- O'Mara, M., Keramidas, A, Barry, P.H., Chung, S.H. Mechanism of ion permeation in the glycine receptor and its cation-selective mutations. Biophys. J. 84(2):93A-93A Part 2 Suppl. S FEB 2003
- Barry, P.H., Keramidas, A., O'Mara, M., Moorhouse, A.J., Schofield, P.R. 2003. Mutant glycine receptor channels, with reversed ion charge selectivities, and analysis of their anion-cation permeabilities. Proceedings of the 14th World Congress on Animal, Plant and Microbial Toxins, P. 123, ASB Abstract No. ASB03 5CM3. No ISSN
- Keramidas, A, Moorhouse, A.J., O'Mara, M., Pierce, K., Schofield, P.R, Chung, S-H, Barry, P.H. 2002. M2 mutations, which switch the ion selectivity of glycine receptor channels and act via both electrostatic effects and changes in minimum pore diameter, and mathematical modelling. Proc. Aust. Health & Med. Res. Congress: 1325. ISSN: 1447-6010
- M.L O'Mara. Making sense of transporter structures. Gordon Research Conference: Multi-Drug Efflux Systems. March 22-27, 2009
- M.L. O’Mara. Simulations of ion permeation through a homology model of the GABAA receptor. Department of Biology, University of Calgary, February 2005.
- M.L. O’Mara. Physics in Medicine. Australian Society of von Humboldt Fellows Colloquium, January 2005.
- M.L. O’Mara, B. Cromer, M. Parker and S.H. Chung. Brownian dynamics simulations of ion permeation through a homology model of the GABAA receptor. The 28th Annual Conference of the Australian Society for Biophysics, 2004.
- M.L. O’Mara, B. Corry, D. Bisset and S.H. Chung, Biophysics of sub-cellular complex systems. COSNET Complex Systems Network Workshop, 2004.
- M.L. O’Mara, B. Corry, D. Bisset and S.H. Chung, Biophysical Problems: ClC chloride ion channels. Gordon Godfrey Workshop, 2003.
- M.L. O’Mara. From function to structure: modeling the Glycine Receptor from its electrophysiology. Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, August 2002.
UQ Postdoctoral Fellow,
Molecular Dynamics Group
School of Chemistry and Molecular Biosciences (SCMB)
Chemistry Building (#68)
The University of Queensland
St. Lucia Campus, Brisbane, QLD 4072
phone: +61 7 3365 7562