Lipid Modulation of Glycine Transporters
Endocannabinoids are a class of lipid-based compounds that have multiple sites of action. One of these compounds, N-arachidonyl-glycine, is analgesic and has potent inhibitory actions on glycine transporters. This project will attempt to understand the mechanism of action of these novel compounds.
Glycine neurotransmission is a recently identified target for the development of novel analgesic drugs and the N-arachidonyl amino acids are a recently described class of endocannabinoids that show particular promise as new pain relievers. We have demonstrated that one of these compounds, N-arachidonyl-glycine has potent effects on glycine transporters and in this project we are attempting to understand how this compound modulates transport function. We will approach this question from both a cellular biology perspective and also in terms of how this compound interacts with the transporter. Fluorescence techniques will be used to study localisation of transporters and how expression patterns can influence actions of N-arachidonylglycine of glycine transporters. At the molecular level, a combination of protein modelling, site directed mutagenesis and electrophysiological techniques will be used to define the sites of interaction between the transporters and N-arachidonylglycine. This project will project will provide an understanding of the basic science behind the actions of these novel compounds and may also lea to the development of novel drugs for the treatment of pain.
Techniques to be used in this project will include: site-directed mutagenesis, protein purification, electrophysiology, computer modeling of protein structures The project is supported by a NHMRC project grant. A top-up scholarship is available for well qualified candidates.
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The opportunity ID for this research opportunity is: 2