Research directions

 The major research interest in the laboratory concerns the molecular structure and function of the structurally-related glycine and GABAA receptor chloride channels that mediate inhibitory neurotransmission in the central nervous system.

The GABAA receptor is an important target for neuroactive drugs and the glycine receptor has recently emerged as a drug target for inflammatory pain. We try to understand the mechanisms by which these receptors open and close, their structure and their molecular pharmacology.

His laboratory is also interested in identifying novel compounds active at these receptors as leads for therapeutic development and as pharmacological tools for basic research. A more complete description of our current research interests is given here.

Experimental approaches include molecular biology, protein chemistry, manual and automated patch-clamp electrophysiology, fluorescence imaging, automated high throughput fluorescence-based screening, voltage-clamp fluorescence (VCF).

Current collaborations

Brett Cromer, RMIT University
Pankaj Sah, University of QLD
Rob Capon, University of QLD
Mark Rees and Seo-kyung Chung, University of Swansea
Daniel Gilbert, University of Erlangen
Robert Harvey, London School of Pharmacy
Richard Evans, University of Leicester
 

Selected publications

Lynch, J.W. 2004. Molecular structure and function of the glycine receptor chloride channel. Physiol. Rev. 84: 1050-1095.

Lynch, J.W. 2009. Native glycine receptor subtypes and their physiological roles. Neuropharmacol. 56: 303-309.

Pless, S.A., and J.W. Lynch. 2009. Ligand-specific conformational changes in the α1 glycine receptor ligand-binding domain. J. Biol. Chem. 284: 15847-15856

Balansa, W., R. Islam, F. Fontaine, A.M. Piggott, H. Zhang, T.I. Webb, D.F. Gilbert, J.W. Lynch, and R.J. Capon. 2010. Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the genus Ircinia. Bioorgan. Med. Chem. 18: 2912-2919.

Lynagh, T., and J.W. Lynch. 2010. An improved ivermectin-activated Cl channel receptor for inhibiting electrical activity in defined neuronal populations. J. Biol. Chem. 285: 14890-14897.

Chung S.-K., J.-F. Vanbellinghen, J.G.L. Mullins, A. Robinson, J. Hantke, C. Hammond, D.F. Gilbert, M. Freilinger, M. Ryan, M. Kruer, A. Masri, C. Gurses, C. Ferrie, K. Harvey, R. Shiang, J. Christodoulou, F. Andermann, R.H. Thomas, R.J. Harvey, J.W. Lynch, and M.I. Rees. 2010. Pathological basis of dominant and recessive GLRA1 mutations in human hyperekplexia. J Neurosci. 30: 9612-9620.

Lynagh, T., and J.W. Lynch. 2010. A glycine residue essential for high ivermectin sensitivity in Cys-loop ion channel receptors. In press Int. J. Parasitol. 40: 1477-1481.

Wang, Q., S.A. Pless, and J.W. Lynch. 2010. Ligand- and subunit-specific conformational changes in the ligand-binding domain and the TM2-TM3 linker of α1β2γ2 GABA-A receptors. J. Biol. Chem. 285: 40373-40386.