Transporter Biology Group

Lab head: Robert Vandenberg
Location: Pharmacology, Blackburn Building

This group investigates the pharmacology and biochemistry of neurotransmitter transporters in the central nervous system. This involves the use of a combination of recombinant DNA and electrophysiological techniques to investigate the molecular basis for the actions of endogenous modulators as well as novel agents on neurotransmitter transporters.

Website: http://www.bosch.org.au/research/NervousSystem/TransporterBiology/index.php
Lab members: R Vandenberg (head), R Ryan (senior), Cheryl Handford (research assistant), Marietta Salim (research assistant), Amelia Edington )PhD student), Tan Sirivant (PhD student)
Funding: NHMRC Project Grant, ARC Discovery Grant
Research approach equipment: Molecular biology, computer modelling, electrophysiology, protein chemistry
Publications:

Recent Selected Publications

Ryan RM, Kortt N, Sirivanta T, Vandenberg RJ  (2010) Journal of Neurochemistry (in press)

Mark Connor, Robert Vandenberg and Christopher Vaughan (2010).   British Journal of Pharmacology (in press)

Amelia Edington, Audra McKinzie, Aaron J. Reynolds, Michael Kassiou, Renae M. Ryan and Robert J. Vandenberg (2009) Journal of Biological Chemistry284:36424-36430

Huang S., Ryan, R.M. and Vandenberg, R.J. (2009) Journal of Biological Chemistry284, 4510-4515 

Robert J Vandenberg, Shiwei Huang and Renae M Ryan (2008). Channels 2, 51-58

Vandenberg R.J., Shaddick K. and Ju P. (2007) The Journal of Biological Chemistry 282, 14447-14453

Wiles A, Pearlman R-J, Rosvall M, Aubrey K and Vandenberg RJ (2006) Journal of Neurochemistry 99, 781-786

Ryan RM, Mitrovic AD and Vandenberg RJ (2004) The Journal of Biological Chemistry 279: 20742-20751

Ju P, Aubrey KR, Vandenberg RJ (2004) The Journal of Biological Chemistry 279: 22983-22991

Mitrovic AD, Plesko F and Vandenberg RJ (2001)..  Journal of Biological Chemistry 276, 26071 - 26076

Aubrey KR and Vandenberg RJ. (2001)  British Journal of Pharmacology 134, 1429-1436

Ryan RM and Vandenberg RJ (2002) The Journal of Biological Chemistry 277, 13494-13500

 


Defining Drug Binding Sites on GLYT1

Primary supervisor: Robert Vandenberg

Research in the Transporter Biology Group is focused on understanding the molecular basis for neurotransmitter transporter functions and how this can be manipulated by endogenous regulators and pharmacological agents.  Glycine is an unusual neurotransmitter in that it acts on inhibitory glycine receptors and excitatory NMDA receptors. The Glycine Transporter GLYT1 regulates the concentrations of glycine at excitatory synapses, whilst a combination of GLYT1 and GLYT2 are required for regulation of glycine at inhibitory synapses. GLYT1 inhibitors are currently under trial for the treatment of schizophrenia, whilst GLYT2 inhibitors may have potential as analgesics in the treatment of chronic pain.

Defining Drug Binding Sites on GLYT1: Although a number of GLYT1 inhibitors are under clinical trials for the treatment of Schizophrenia, very little is known about their mechanism of inhibition of GLYT1 or how they interact with the transporter. In this project you will characterize the binding sites on GLYT1 for a series of novel GLYT1 inhibitors.  Figure on right is of the drug, clomipramine bound to the leucine transporter, LeuT.  Similar models will be generated for GLYT1 to identify drug binding sites. The models will be tested by site-directed mutagenesis combined with electrophysiology techniques.

 

 

 

 

 

 

 

 

 


Discipline: Pharmacology
Co-supervisors: Renae Ryan
Keywords: Neuropharmacology, Molecular biology, Drug design
Contact: Email Robert Vandenberg