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Professor Megan O'Mara

Professorial Research Fellow and Gr

Australian Institute for Bioengineering and Nanotechnology
m.omara@uq.edu.au

Overview

Megan O’Mara is a Professor and Group Leader at the Australian Institute for Bioengineering and Nanotechnology (AIBN), UQ. Her group uses multiscale modelling techniques to understand how changes in the biochemical environment of the cell membranes alters membrane properties and modulates the function of membrane proteins. She has research interests in multidrug resistance, computational drug design and delivery, biopolymers, and personalized medicine. Megan completed her PhD in biophysics at the Australian National University in 2005 before moving to the University of Calgary, Canada, to take up a Canadian Institutes of Health Research Postdoctoral Fellowship. In 2009, she returned to Australia to join University of Queensland’s School of Chemistry and Molecular Biosciences as a UQ Postdoctoral Fellow, before commencing an ARC DECRA in 2012 where she continued her computational work on membrane protein dynamics. In 2015, Megan joined the Research School of Chemistry, Australian National University in 2015 as Rita Cornforth Fellow and Senior Lecturer. In 2019 she was promoted to Associate Professor and was Associate Director (Education) of the Research School of Chemistry ANU in 2019-2021. In April 2022 she relocated to AIBN.

Research Interests

  • computational drug design
    computational drug design, structure based drug design, structure activity relationships, computational fragment based drug design
  • membrane biophysics
    computational cell membrane biophysics, computational lipidomics, cell membrane properties in health, disease and senescence
  • multudrug resistance
    antimicrobial resistance, cancer chemotherapy resistance
  • polymer simulations
    biopolymers, self assembly, polymer properties
  • lipid delivery systems
    targeted lipid delivery systems, computational analysis, lipid formulations, LNP loading, computational simulations
  • computational structural biology
    membrane protein structure-function, computational biology, protein structure prediction

Research Impacts

My research uses computational techniques and simulations to understand how the chemistry of biological and bioinspired systems influence their physical properties. My goal is to understand how biomolecules self-assemble and self-regulate in living cells. My work allows the rational design of new pharmaceuticals, drug and vaccine delivery systems and biocompatable materials, as well as understanding fundamental problems such as antibiotic resistance. My students gain skills in data science, computational chemistry, computational biology, high performance computing, rational drug design and research data management that are directly transferable to industry, government and policy development, as well as research. I collaborate broadly across UQ, Australia and internationally with researchers and industry.

Qualifications

  • Bachelor of Applied Science, University of Canberra
  • Bachelor of Science (Physical Sciences), Australian National University
  • PhD (Physical Sciences), Australian National University

Publications

  • Journal Article: The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias

    Chen, Wenqian, Wang, Ruiwu, Chen, Biyi, Zhong, Xiaowei, Kong, Huihui, Bai, Yunlong, Zhou, Qiang, Xie, Cuihong, Zhang, Jingqun, Guo, Ang, Tian, Xixi, Jones, Peter P., O'Mara, Megan L., Liu, Yingjie, Mi, Tao, Zhang, Lin, Bolstad, Jeff, Semeniuk, Lisa, Cheng, Hongqiang, Zhang, Jianlin, Chen, Ju, Tieleman, D. Peter, Gillis, Anne M., Duff, Henry J., Fill, Michael, Song, Long-Sheng and Chen, S. R. Wayne (2014). The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias. Nature Medicine, 20 (2), 184-192. doi: 10.1038/nm.3440

  • Journal Article: Imperfect coordination chemistry facilitates metal ion release in the Psa permease

    Couñago, Rafael M., Ween, Miranda P., Begg, Stephanie L., Bajaj, Megha, Zuegg, Johannes, O'Mara, Megan L., Cooper, Matthew A., McEwan, Alastair G., Paton, James C., Kobe, Bostjan and McDevitt, Christopher A. (2014). Imperfect coordination chemistry facilitates metal ion release in the Psa permease. Nature Chemical Biology, 10 (1), 35-41. doi: 10.1038/nCHeMBIO.1382

  • Journal Article: The effect of environment on the structure of a membrane protein: P-glycoprotein under physiological conditions

    O’Mara, Megan L. and Mark, Alan E. (2012). The effect of environment on the structure of a membrane protein: P-glycoprotein under physiological conditions. Journal of Chemical Theory and Computation, 8 (10), 3964-3976. doi: 10.1021/ct300254y

View all Publications

Grants

View all Grants

Supervision

  • Computational design of targeted lipid technologies

    Doctor Philosophy

  • The effect of membrane composition on protein-ligand interactions in drug design and delivery

    Doctor Philosophy

  • Targeting alterations in cell membrane biophysics for disease intervention

    Doctor Philosophy

View all Supervision

Available Projects

  • The impact of lipid modifications on cell membrane function

    Membrane lipid composition influences the localisation of membrane proteins and regulates their activity. The hundreds of chemically distinct lipids within cell membranes phase-separate to form microdomains that impact the localisation and interactions of membrane proteins. The composition of the cell membrane is tightly controlled in normal cellular function. There is now considerable evidence that altered cell homeostasis, ranging from inflammatory processes to cancer, cause alterations in metabolic pathways which impact membrane lipid distributions, cell biophysical properties and membrane protein function. This may have downstream impacts on the uptake and efficacy of a range of pharmaceuticals used to treat dysfunction. Using data derived from mass spectrometry and other experimental approaches, this project will use multiscale simulation techniques to examine how changes in lipid membrane composition in cancer and other disease states impacts drug uptake. This knowledge will provide a means to specifically target a given cell type through the drug delivery systems and targeted therapeutics.

  • Membrane mediated antimicrobial resistance

    Bacterial multidrug efflux pumps are the bacteria’s first line of defence against the action of antimicrobials. However, very little is currently known about the function and substrate range of these efflux pumps. This project will examine different multidrug efflux pumps to uncover the structural basis of substrate specificity and transport. It will examine the impact of bacterial membrane modifications on bacterial multidrug efflux pump function, and how peptide- and/or polymer-based antimicrobials inhibit multidrug efflux pumps and disrupt membrane integrity. Other avenues of investigation include characterising the effect of lipid modifications in antimicrobial resistance, and computational drug design of lead new candidates for antimicrobial design. This project uses a range of computational techniques, primarily multiscale molecular dynamics simulations.

  • Computational design of biocompatable delivery systems

    Biocompatible delivery systems allow enhanced delivery of pharmaceuticals, vaccines and other biological payload molecules, with varied effects including extending the pharmaceutical half-life of drugs, increasing adsorption and decreasing immunogenicity. While these agents have increased the efficacy of many biological therapies, very little work has been done on improving the targeting of these agents to the specific cell or receptor of interest. This project will examine strategies to increase the selectivity of biopolymer delivery systems to enhance the ability to target specific cell types or receptors, thereby reducing off target effects. This project will identify the chemical composition and biophysical characteristics of different cell membranes, and how this impacts their interaction with biopolymer delivery systems. The project requires good collaboration skills, an broad understanding of chemistry and biochemistry, and strong skills in multiscale modelling techniques, from QMMM to coarse grained molecular dynamics.

View all Available Projects

Publications

Featured Publications

  • The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias

    Chen, Wenqian, Wang, Ruiwu, Chen, Biyi, Zhong, Xiaowei, Kong, Huihui, Bai, Yunlong, Zhou, Qiang, Xie, Cuihong, Zhang, Jingqun, Guo, Ang, Tian, Xixi, Jones, Peter P., O'Mara, Megan L., Liu, Yingjie, Mi, Tao, Zhang, Lin, Bolstad, Jeff, Semeniuk, Lisa, Cheng, Hongqiang, Zhang, Jianlin, Chen, Ju, Tieleman, D. Peter, Gillis, Anne M., Duff, Henry J., Fill, Michael, Song, Long-Sheng and Chen, S. R. Wayne (2014). The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias. Nature Medicine, 20 (2), 184-192. doi: 10.1038/nm.3440

  • Imperfect coordination chemistry facilitates metal ion release in the Psa permease

    Couñago, Rafael M., Ween, Miranda P., Begg, Stephanie L., Bajaj, Megha, Zuegg, Johannes, O'Mara, Megan L., Cooper, Matthew A., McEwan, Alastair G., Paton, James C., Kobe, Bostjan and McDevitt, Christopher A. (2014). Imperfect coordination chemistry facilitates metal ion release in the Psa permease. Nature Chemical Biology, 10 (1), 35-41. doi: 10.1038/nCHeMBIO.1382

  • The effect of environment on the structure of a membrane protein: P-glycoprotein under physiological conditions

    O’Mara, Megan L. and Mark, Alan E. (2012). The effect of environment on the structure of a membrane protein: P-glycoprotein under physiological conditions. Journal of Chemical Theory and Computation, 8 (10), 3964-3976. doi: 10.1021/ct300254y

Book Chapter

  • Method for developing optical sensors using a synthetic dye-fluorescent protein FRET pair and computational modeling and assessment

    Mitchell, Joshua A., Zhang, William H., Herde, Michel K., Henneberger, Christian, Janovjak, Harald, O’Mara, Megan L. and Jackson, Colin J. (2017). Method for developing optical sensors using a synthetic dye-fluorescent protein FRET pair and computational modeling and assessment. Synthetic Protein Switches: Methods and Protocols. (pp. 89-99) New York, NY, United States: Humana Press. doi: 10.1007/978-1-4939-6940-1_6

  • Thylakoid ultrastructure: visualizing the photosynthetic machinery

    Steinbeck, Janina, O’Mara, Megan L., Ross, Ian L., Stahlberg, Henning and Hankamer, Ben (2017). Thylakoid ultrastructure: visualizing the photosynthetic machinery. Chlamydomonas: Biotechnology and Biomedicine. (pp. 149-191) edited by Michael Hippler. Cham, Switzerland: Springer International Publishing. doi: 10.1007/978-3-319-66360-9_7

  • Polypeptide and protein modeling for drug design

    O’Mara, Megan L. and Deplazes, Evelyne (2014). Polypeptide and protein modeling for drug design. Encyclopedia of computational neuroscience. (pp. 1-9) New York, United States: Springer . doi: 10.1007/978-1-4614-7320-6_732-1

  • Polypeptide and protein modeling for drug design

    O'Mara, Megan and Deplazes, Evelyne (2014). Polypeptide and protein modeling for drug design. Encyclopedia of computational neuroscience. (pp. 2439-2447) edited by Dieter Jaeger and Ranu Jung. Berlin, Germany: Springer. doi: 10.1007/978-1-4614-6675-8_732

Journal Article

Conference Publication

  • Going downstream - how does GH binding activate JAK2

    Brooks, Andrew, Dai, W., O'Mara, M. L., Abankwa, D., Chhabra, Y., Pelekanos, R. A., Gardon, O., Tunny, K. A., Blucher, K. M., Morton, C. J., Parker, M. W., Sierecki, E., Gambin, Y., Gomez, G. A., Alexandrov, K., Wilson, I. A., Doxastakis, M., Mark, A. E. and Waters, M. J. (2016). Going downstream - how does GH binding activate JAK2. Annual Scientific Meeting of the Endocrine Society of Australia, Adelaide, Australia, 23-26 August, 2015. Chichester, West Sussex, United Kingdom: Wiley-Blackwell Publishing. doi: 10.1111/cen.13010

  • Mechanism of JAK2 Activation by the Archetype Class I Cytokine Receptor, the Growth Hormone Receptor

    Brooks, Andrew J., O’Mara, Megan L., Dai, Wei, Abankwa, Daniel, Chhabra, Yash, Tunny, Kathryn A., Parker, Michael W., Sierecki, Emma, Gambin, Yann, Gomez, Guillermo A., Haxholm, Gitte W., Nikolajsen, Louise F., Doxastakis, Manolis, Mark, Alan E. and Waters, Michael J. (2016). Mechanism of JAK2 Activation by the Archetype Class I Cytokine Receptor, the Growth Hormone Receptor. Biophysical Meeting, Los Angeles, CA, United States, 27 February - 2 March 2016. CAMBRIDGE: CELL PRESS. doi: 10.1016/j.bpj.2015.11.233

  • Insights into the operations of a promiscuous drug trafficker: The story of P-glycoprotein

    Condic-Jurkic, K., Subramanian, N., Mark, A. E. and O'Mara, M. (2015). Insights into the operations of a promiscuous drug trafficker: The story of P-glycoprotein. 10th European Biophysical Societies Association (EBSA) European Biophysics Congress, Dresden, Germany, 18-22 July 2015. Heidelberg, Germany: Springer. doi: 10.1007/s00249-015-1045-6

  • A new cytokine receptor activation paradigm: Activation of JAK2 by the growth hormone receptor

    Brooks, Andrew J, Chhabra, Yash, Abankwa, Daniel, O’Mara, Megan, Dai, Wei, Gardon, Olivier, Tunny, Kathryn A., Blucher, Kristopher M., Morton, Craig J., Parker, Michael W., Sierecki, Emma, Gambin, Yann, Guillermo A. Gomez, Alexandrov, Kirill Kirill, Doxastakis, Manolis, Mark, Alan E. and Waters, Michael J. (2014). A new cytokine receptor activation paradigm: Activation of JAK2 by the growth hormone receptor. 2nd Annual Meeting of the International Cytokine and Interferon Society (ICIS), Melbourne, VIC Australia, 26 - 29 October 2014. London, United Kingdom: Academic Press. doi: 10.1016/j.cyto.2014.07.227

  • Chicken TAP genes are polymorphic and co-evolve with the dominantly-expressed class I gene

    Sowa, Anna, Harrison, Michael, Tregaskes, Clive, Chappell, Paul, Roversi, Pietro, Lea, Susan, O'Mara, Megan, Gaudet, Rachelle and Kaufman, Jim (2012). Chicken TAP genes are polymorphic and co-evolve with the dominantly-expressed class I gene. 7th Biannual Workshop on Antigen Presentation, Amsterdam, Netherlands, 24-27 April 2012. Oxford, United Kingdom: Pergamon. doi: 10.1016/j.molimm.2012.02.050

  • Determining the structural conformation of P-glycoprotein via homology modelling

    O'Mara, M. L. and Tieleman, D. P. (2007). Determining the structural conformation of P-glycoprotein via homology modelling. 51st Annual Meeting of the Biophysical-Society, Baltimore, United States, 3-7 March 2007. St. Louis, United States: Cell Press.

  • Computer simulations of ABC transporter components

    Oloo, Eliud, Kandt, Christian, O’Mara, Megan L. and Tieleman, D. Peter (2006). Computer simulations of ABC transporter components. 49th Annual Canadian Society of Biochemistry and Molecular and Cellular Biology Meeting, Ontario, Canada, 31 May- 4 June 2006. Ottowa, Canada: National Research Council of Canada. doi: 10.1139/O06-182

  • Investigating the mechanism of proton transfer through the bacterial ClC transporter

    O'Mara, Megan L., Yin, Jian, Hoyles, Matthew and Chung, Shin-Ho (2006). Investigating the mechanism of proton transfer through the bacterial ClC transporter. 50th Annual Meeting of the Biopysical-Society, Salt Lake City, Utah, U.S.A., 18-22 February, 2006. Bethesda, MD., U.S.A.: Cell Press for the Biophysical Society.

  • The reliability of relative cation-anion permeabilities deduced from reversal (dilution) potential measurements in ion channel studies, and Brownian dynamics predictions

    Barry, PH and O'Mara, ML (2005). The reliability of relative cation-anion permeabilities deduced from reversal (dilution) potential measurements in ion channel studies, and Brownian dynamics predictions. Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences, San Diego Ca, Mar 31-Apr 06, 2005. BETHESDA: FEDERATION AMER SOC EXP BIOL.

  • Simulations of ion permeation through a homology model of the GABA(A) receptor

    O'Mara, ML, Cromer, BA, Parker, MW and Chung, SH (2005). Simulations of ion permeation through a homology model of the GABA(A) receptor. 49th Annual Meeting of the Biopysical-Society, Long Beach Ca, Feb 12-16, 2005. BETHESDA: BIOPHYSICAL SOCIETY.

  • Simulations of ion permeation through a homology model of the GABA(A) receptor

    O'Mara, M. L., Cromer, B. A., Parker, M. W. and Chung, S. H. (2005). Simulations of ion permeation through a homology model of the GABA(A) receptor. 49th Annual Meeting of the Biopysical-Society, Long Beach, California, U.S.A., 12-16 February, 2005. Bethesda, MD., U.S.A.: Cell Press for the Biophysical Society.

  • The reliability of relative cation-anion permeabilities deduced from reversal (dilution) potential measurements in ion channel studies, and Brownian dynamics predictions

    Barry, P. H. and O'Mara, M. L. (2005). The reliability of relative cation-anion permeabilities deduced from reversal (dilution) potential measurements in ion channel studies, and Brownian dynamics predictions. Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences, San Diego, California, U.S.A., 31 March, - April, 2005. Bethesda, MD, U.S.A.: Federation of American Societies for Experimental Biology.

  • Mechanisms of chloride conduction in ClC channels

    Corry, B., O'Mara, M., Bisset, D. and Chung, S. H. (2004). Mechanisms of chloride conduction in ClC channels. 48th Annual Meeting of the Biophysical Society, Baltimore, Maryland, USA, 14-18 February 2004. Bethesda, MD: Pubmed Central.

  • Mechanisms of chloride conduction in ClC channels

    Corry, B, O'Mara, M, Bisset, D and Chung, SH (2004). Mechanisms of chloride conduction in ClC channels. 48th Annual Meeting of the Biophysical Society, Baltimore Md, Feb 14-18, 2004. BIOPHYSICAL SOCIETY.

  • Mechanism of ion permeation in the glycine receptor and its cation-selective mutations

    O'Mara, Megan, Keramidas, Angelo, Barry, Peter H. and Chung, Shin-Ho (2003). Mechanism of ion permeation in the glycine receptor and its cation-selective mutations. 47th Annual Meeting of the Biophysical Society, San Antonio, Texas, 1-5 March 2003. Bethesda, MD, U.S.A.: Cell Press for the Biophysical Society.

  • Mechanism of ion permeation in the glycine receptor and its cation-selective mutations

    O'Mara, M., Keramidas, A., Barry, P. H. and Chung, S. H. (2003). Mechanism of ion permeation in the glycine receptor and its cation-selective mutations. 47th Annual Meeting of the Biophysical-Society, San Antonio Texas, 1-5 March 2003. Bethesda, MD United States: Biophysical Society.

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Computational design of targeted lipid technologies

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • The effect of membrane composition on protein-ligand interactions in drug design and delivery

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • Targeting alterations in cell membrane biophysics for disease intervention

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • Allosteric modulation of synaptic proteins by endogenous and modified sterols

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • Molecular basis of membrane-mediated antimicrobial resistance.

    Doctor Philosophy — Associate Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • The impact of lipid modifications on cell membrane function

    Membrane lipid composition influences the localisation of membrane proteins and regulates their activity. The hundreds of chemically distinct lipids within cell membranes phase-separate to form microdomains that impact the localisation and interactions of membrane proteins. The composition of the cell membrane is tightly controlled in normal cellular function. There is now considerable evidence that altered cell homeostasis, ranging from inflammatory processes to cancer, cause alterations in metabolic pathways which impact membrane lipid distributions, cell biophysical properties and membrane protein function. This may have downstream impacts on the uptake and efficacy of a range of pharmaceuticals used to treat dysfunction. Using data derived from mass spectrometry and other experimental approaches, this project will use multiscale simulation techniques to examine how changes in lipid membrane composition in cancer and other disease states impacts drug uptake. This knowledge will provide a means to specifically target a given cell type through the drug delivery systems and targeted therapeutics.

  • Membrane mediated antimicrobial resistance

    Bacterial multidrug efflux pumps are the bacteria’s first line of defence against the action of antimicrobials. However, very little is currently known about the function and substrate range of these efflux pumps. This project will examine different multidrug efflux pumps to uncover the structural basis of substrate specificity and transport. It will examine the impact of bacterial membrane modifications on bacterial multidrug efflux pump function, and how peptide- and/or polymer-based antimicrobials inhibit multidrug efflux pumps and disrupt membrane integrity. Other avenues of investigation include characterising the effect of lipid modifications in antimicrobial resistance, and computational drug design of lead new candidates for antimicrobial design. This project uses a range of computational techniques, primarily multiscale molecular dynamics simulations.

  • Computational design of biocompatable delivery systems

    Biocompatible delivery systems allow enhanced delivery of pharmaceuticals, vaccines and other biological payload molecules, with varied effects including extending the pharmaceutical half-life of drugs, increasing adsorption and decreasing immunogenicity. While these agents have increased the efficacy of many biological therapies, very little work has been done on improving the targeting of these agents to the specific cell or receptor of interest. This project will examine strategies to increase the selectivity of biopolymer delivery systems to enhance the ability to target specific cell types or receptors, thereby reducing off target effects. This project will identify the chemical composition and biophysical characteristics of different cell membranes, and how this impacts their interaction with biopolymer delivery systems. The project requires good collaboration skills, an broad understanding of chemistry and biochemistry, and strong skills in multiscale modelling techniques, from QMMM to coarse grained molecular dynamics.

  • Allosteric modulation of synaptic transmission by neurosteroids and oxysterols

    The development of effective therapeutics that target chronic pain in neurological diseases would significantly improve the quality of life for millions of people living with chronic pain. The glycinergic neuronal transport proteins are a promising target for the treatment of chronic pain. In neurons and other cells, the membrane lipid composition influences the localisation of membrane proteins and regulates their activity. The hundreds of chemically distinct lipids within cell membranes phase-separate to form microdomains that impact the localisation and interactions of membrane proteins. Oxidative stress is an early hallmark of inflammation and disease that causes chemical modifications to membrane lipids, proteins, and other biomolecules. This impacts their function and influences their biophysical properties. This project will examine the effect of oxysterols and neurosteroids on the inhibition of glycernergic synaptic membrane proteins for the development of targeted therapeutics for the treatment of chronic pain in specific disease states. This is a computational project. The direction of the project can be tailored to the interests of the student.

This staff member is a UQ Expert for media in the following fields:

supercomputers - applications, computational chemistry, biophysics, drug design, women in STEM

They are happy to lend their expertise to your articles or broadcasts and share their research discoveries and insights with the community via media channels.

For additional assistance with story ideas, general advice and information or help with seeking further experts, please email the UQ Media Team or telephone (07) 3365 1120.

Links

ResearcherID: A-4962-2011

ORCID: 0000-0002-8764-1585

Scopus ID: 16053076100

Google Scholar ID: 9lJquJQAAAAJ

Personal Profile: Link

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