B Appl Sc (UC) Medical Laboratory Science, B Sc (ANU) Physics, PhD (ANU) Physical Sciences
Position: 
ARC Discovery Early Career Researcher
Room: 
327
Phone: 
+61 7 336-54638
Biography: 

 

I was awarded my PhD from the ANU in 2005, where I studied ion channel permeation using Langevin Dynamics simulations. Shortly after being awarded my PhD, I accepted a Canadian Institutes of Health Research Postdoctoral Fellowship to work with Prof. Peter Tieleman at the University of Calgary. In 2009, I commenced a University of Queensland Postdoctoral Fellowship and joined the group of Prof. Alan Mark. I was awarded an ARC Discovery Early Career Researcher Award, which I commenced in 2012.

Research Focus and Collaborations: 

 

Our research focus is structure-function investigations of membrane transport proteins which we perform using computational techniques. Membrane transport proteins control the flow of nutrients, hormones, signalling molecules, drugs and other substrates across the cell membrane. They play a vital role in regulating and controlling the concentration and cellular accumulation of these molecules. Membrane proteins play such an important role in cellular function that they account of ~30% of our DNA. One major membrane transport family is the ABC transporter superfamily.

ABC transporters are found in all organisms. Mutations in, or over-expression of, ABC transporters is associated with many disease processes, ranging from cystic fibrosis and macular degeneration, to antibiotic resistance in bacteria and chemotherapy resistance in humans. Despite the medical importance of ABC transporters, the way ABC transporters bind and transport their substrates out of the cell remains unknown. Our research investigates the structural dynamics of ABC transporters, in particular the human multidrug transporter P-glycoprotein. The over-expression of P-glycoprotein in cancers induces chemotherapy resistance, one of the most common causes of cancer-related death. While inhibitors of P-glycoprotein have been developed, all have failed at or before clinical trials due to toxic side effects caused by the disruption of normal P-glycoprotein function. Using computational simulations, we are investigating the mechanism of drug binding by P-glycoprotein and how P-glycoprotein transports drugs across the cell membrane. Understanding the nature of drug binding and determining the physical location of the drug binding sites may help in the development of selective inhibitors that selectively overcome chemotherapy resistance while still retaining endogenous P-glycoprotein function.

Funded Projects: 

Grants and Awards:

ARC Discovery Project. 2013-2016.  Membrane proteins: Understanding biological switches, motors and triggers. AE Mark and ML O'Mara. 

NHMRC Project Grant. 2013- 2016. Understanding multidrug resistance in cancer: identification of the substrate and inhibitor binding sites in P-glycoprotein. M.L. O'Mara, AE Mark and R Callaghan.

ARC Discovery Early Career Researcher Award. 2012- 2015. Understanding multidrug resistance: identifying the molecular basis of substrate and inhibitor transport by P-glycoprotein. ML O'Mara.

University of Queensland Early Career Research Grant. 2010.  The mechanism of viral entry into cells: understanding how Glycoprotein 2 from Ebola initiates membrane fusion. ML O'Mara.

Association for International Cancer Research Project grant. How do drugs bind to the multidrug resistance P-glycoprotein? 2012-2015. R Callaghan, ML O’Mara, F McMillan, ID Kerr.

National Health and Medical Research Council Project Grant. 2010-2012. The role of the glutamine transporter SNAT3 in ion transport, cell signalling and ammonia detoxification. S Broer, J Deitmer, C Wagner, ML O’Mara.

National Computational Infrastructure Merit Allocation Scheme. 2010 – present.

Fellowships:

University of Queensland Postdoctoral Fellowship. 2009-2012. Transporting molecules across biological membranes: Modelling structural changes within the P-glycoprotein transport cycle. ML O'Mara.

Canadian Institute of Health Research (CIHR) Postdoctoral Fellowship. 11/2005-2009. Molecular dynamics simulations of vitamin B12 permeation through the BtuCD ABC transporter.

 

 

Teaching: 

BIPH2000, BIPH3001

Selected Publications: