Bioactive Lipid Modulation of Glycine Transporters and Glycine Receptors

Summary

A major focus of our work is on the design, synthesis and development of new bioactive lipids that inhibit glycine transporters. These compounds represent a new class of allosteric transport inhibitors and show considerable potential as analgesics for the treatment of chronic pain.

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 and the N-arachidonyl amino acids are a recently described class of endocannabinoids that show particular promise as new pain relievers. We have developed a multi-pronged approach to drug development: medicinal chemistry; protein structure and function studies; in silico molecular dynamics simulations; and we collaborate with Mac Christie, Karin Aubrey and Sarasa Mohammadi to understand how these compounds alter glycinergic neurotransmission and alleviate pain. We are also working with Michael Murray's group to investigate the pharmacokinetic properties of these compounds with the aim of developing drugs that can be used in the clinic for the treatment of chronic pain. The group has also recently discovered a series of compounds that allosterically stimulate the activity of Glycine Receptors and we are investigating how they modulate receptor function and also the therapeutic potential of these compounds.

Additional Information

Techniques to be used in this project will include: medicinal chemistry, site-directed mutagenesis, protein purification, electrophysiology, computer modeling of protein structures and lipid interactions. The project is supported by an NHMRC project grant. We can offer a range of projects depending on students interests and I encourage students with interests in Biochemistry, Neuroscience, Physiology or Molecular Biology to contact me.

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Keywords

Pain, analgesics, Glycine transporters, molecular biology, endocannabinoids, Brain & nervous system disorders, Cell biology, Neuroscience & psychology, Pharmacology & therapeutics

Opportunity ID

The opportunity ID for this research opportunity is: 2