Discovery and Development of Allosteric Modulators of Glycine Transporters and Glycine Receptors for the Treatment of Chronic Pain

Summary

We offer a variety projects around the discovery and development of new allosteric modulators of glycine transporters and receptors for the treatment of chronic pain. We use a comprehensive approach that involves collaborative projects in protein structure-function analysis, drug screening and drug design, molecular dynamics simulations, animal behavior analysis.

Supervisor(s)

Professor Robert Vandenberg

Research Location

Camperdown - School of Medical Sciences - Bosch Institute

Program Type

Masters/PHD

Synopsis

Glycine neurotransmission is a recently identified target for the development of novel analgesic drugs. Our work focusses on understanding the structure and function of glycine transporters and receptors and using this information to design novel allosteric modulators of these proteins. We have developed a multi-pronged approach to drug development: medicinal chemistry; drug screening, and protein structure - function studies. We collaborate with Mac Christie, Karin Aubrey and Sarasa Mohammadi at the University of Sydney to understand how these compounds alter glycinergic neurotransmission and alleviate pain. We also collaborate with researchers at ANU to conduct molecular dynamics simulations, with scientists at Atomwise Pty Ltd, (San Francisco) to conduct in silco drug screening, and medicinal chemists in New York to fine tune drug design. The aim of this work is to develop drugs that can be used in the clinic for the treatment of chronic pain.

Additional Information

Techniques to be used in the project include: molecular biology, site-directed mutagenesis, electrophysiology, protein purification, cryoEM structural analysis, protein structure modelling. The work is supported by a NHMRC Project Grant, a NIH RO1 grant from the NIH (USA), and Atomwise Pty Lyd. The project would suit students with interests in Biochemistry, Neuroscience, Physiology, Pharmacology.

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Keywords

Neurotransmitter Transporters, Neurotransmitter Receptors, glycine, Inhibitory Neurotransmission, Protein Structure and Function, drug discovery, Drug development, chronic pain, neuropathic pain, Site-directed mutagenesis, Cyro-electron microscopy, analgesia

Opportunity ID

The opportunity ID for this research opportunity is: 2