Molecular neuroscience

About

The Lynch laboratory’s major research interest concerns the molecular structure and function of the glycine and GABAA receptor (GABAAR) chloride channels that mediate inhibitory neurotransmission in the brain. The GABAAR is an important therapeutic target for sedative and anxiolytic drugs and the glycine receptor (GlyR) has recently emerged as a therapeutic target for pain, spasticity, epilepsy and tinnitus. The Lynch laboratory is discovering new drugs active at these receptors and the molecular mechanisms by which their structures and functions are disrupted in hereditary neurological disorders.

The ability to remotely control neuronal activity holds promise for treating human neurological disorders caused by aberrant activity levels, including motor neuron disease, Parkinson’s disease, addiction, anxiety and epilepsy. Previous research in the laboratory led to the development of an improved “neuronal silencing receptor” for inhibiting electrical activity in defined populations of neurons in behaving animals. More recently the laboratory has developed a “neuronal activating receptor” for activating defined neuron populations in the brain. This complements the silencing approach and offers a new tool for defining how the brain works in health and disease.

As synaptic GABAARs are formed from a wide variety of subunits, many isoforms are possible in vivo. Each isoform exhibits unique pharmacological and physiological properties, and has a unique role in brain function. The Lynch group recently developed techniques for reliably generating “artificial” inhibitory synapses that incorporate the defined GABAAR subunits of interest. The group found that synaptic GABAARs incorporating γ1 and γ2 subunits exhibit very different functional properties. Using high-resolution imaging to track the movement of these receptors in real time, the group found that they move at different rates on the cell surface. This may contribute to their differing functional properties.

Contact

  +61 7 334 66375

  j.lynch@uq.edu.au


Group Publications

Research Areas

  • Molecular structure and function of the glycine and GABAA receptor (GABAAR) chloride channels
  • Motor Neurone Disease, Parkinson’s disease, addiction, anxiety, epilepsy
  • Neuronal silencing and activating receptors


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Group Leader

  • Professor Joseph Lynch

    Professor
    Queensland Brain Institute
    Affiliate Research Fellow
    Institute for Molecular Bioscience

Research Members


Students


Ivermectin-activated, cation-permeable glycine receptors for the chemogenetic control of neuronal excitation

Islam, Robiul, Keramidas, Angelo, Xu, Li, Durisic, Nela, Sah, Pankaj and Lynch, Joseph W. (2016) Ivermectin-activated, cation-permeable glycine receptors for the chemogenetic control of neuronal excitation. ACS Chemical Neuroscience7 12: 1647-1657. doi:10.1021/acschemneuro.6b00168

The free zinc concentration in the synaptic cleft of artificial glycinergic synapses rises to at least 1 µm

Zhang, Yan, Keramidas, Angelo and Lynch, Joseph W. (2016) The free zinc concentration in the synaptic cleft of artificial glycinergic synapses rises to at least 1 µm. Frontiers in Molecular Neuroscience9 SEP2016: . doi:10.3389/fnmol.2016.00088

Investigating the mechanism by which gain-of-function mutations to the a1 glycine receptor cause hyperekplexia

Zhang, Yan, Bode, Anna, Nguyen, Bindi, Angelo Keramidas and Lynch, Joseph W. (2016) Investigating the mechanism by which gain-of-function mutations to the a1 glycine receptor cause hyperekplexia. Journal of Biological Chemistry291 29: 15332-15341. doi:10.1074/jbc.M116.728592

Generation of functional inhibitory synapses incorporating defined combinations of GABA(A) or glycine receptor subunits

Dixon, Christine L., Zhang, Yan and Lynch, Joseph W. (2015) Generation of functional inhibitory synapses incorporating defined combinations of GABA(A) or glycine receptor subunits. Frontiers in Molecular Neuroscience8 DEC: . doi:10.3389/fnmol.2015.00080

Xenopus borealis as an alternative source of oocytes for biophysical and pharmacological studies of neuronal ion channels

Cristofori-Armstrong, Ben, Soh, Ming S., Talwar, Sahil, Brown, Darren L., Griffin, John D. O., Dekan, Zoltan, Stow, Jennifer L., King, Glenn F., Lynch, Joseph W. and Rash, Lachlan D. (2015) Xenopus borealis as an alternative source of oocytes for biophysical and pharmacological studies of neuronal ion channels. Scientific Reports5 14763.1-14763.12. doi:10.1038/srep14763

Functional characterization of ivermectin binding sites in α1β2γ2L gaba(A) receptors

Estrada-Mondragon, Argel and Lynch, Joseph W. (2015) Functional characterization of ivermectin binding sites in α1β2γ2L gaba(A) receptors. Frontiers in Molecular Neuroscience8 September: . doi:10.3389/fnmol.2015.00055

Selective modulators of α5-containing GABAA receptors and their therapeutic significance

Soh, Ming Shiuan and Lynch, Joseph W. (2015) Selective modulators of α5-containing GABAA receptors and their therapeutic significance. Current Drug Targets16 7: 735-746. doi:10.2174/1389450116666150309120235

A novel anticonvulsant mechanism via inhibition of complement receptor C5ar1 in murine epilepsy models

Benson, Melissa J, Thomas, Nicola K, Talwar, Sahil, Hodson, Mark P, Lynch, Joseph W, Woodruff, Trent M and Borges, Karin (2015) A novel anticonvulsant mechanism via inhibition of complement receptor C5ar1 in murine epilepsy models. Neurobiology of Disease76 87-97. doi:10.1016/j.nbd.2015.02.004

Investigating ion channel conformational changes using voltage clamp fluorometry

Talwar, Sahil and Lynch, Joseph W. (2015) Investigating ion channel conformational changes using voltage clamp fluorometry. Neuropharmacology98 3-12. doi:10.1016/j.neuropharm.2015.03.018

Correlating structural and energetic changes in glycine receptor activation

Scott, Suzanne, Lynch, Joseph W and Keramidas, Angelo (2015) Correlating structural and energetic changes in glycine receptor activation. Journal of Biological Chemistry290 9: 5621-5634. doi:10.1074/jbc.M114.616573

Functional reconstitution of glycinergic synapses incorporating defined glycine receptor subunit combinations

Zhang, Yan, Dixon, Christine L., Keramidas, Angelo and Lynch, Joseph W. (2015) Functional reconstitution of glycinergic synapses incorporating defined glycine receptor subunit combinations. Neuropharmacology89 391-397. doi:10.1016/j.neuropharm.2014.10.026

Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity

Dixon, Christine L., Harrison, Neil L., Lynch, Joseph W. and Keramidas, Angelo (2015) Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity. British Journal of Pharmacology172 14: 3522-3536. doi:10.1111/bph.13142

The prokaryote ligand-gated ion channel ELIC captured in a pore blocker-bound conformation by the Alzheimer's disease drug memantine

Ulens, Chris, Spurny, Radovan, Thompson, Andrew J., Alqazzaz, Mona, Debaveye, Sarah, Han, Lu, Price, Kerry, Villalgordo, Jose M., Tresadern, Gary, Lynch, Joseph W. and Lummis, Sarah C. R. (2014) The prokaryote ligand-gated ion channel ELIC captured in a pore blocker-bound conformation by the Alzheimer's disease drug memantine.Structure22 10: 1399-1407. doi:10.1016/j.str.2014.07.013

GABAa receptor α and γ subunits shape synaptic currents via different mechanisms

Dixon, Christine, Sah, Pankaj, Lynch, Joseph W. and Keramidas, Angelo (2014) GABAa receptor α and γ subunits shape synaptic currents via different mechanisms. Journal of Biological Chemistry289 9: 5399-5411. doi:10.1074/jbc.M113.514695

The impact of human hyperekplexia mutations on glycine receptor structure and function

Bode, Anna and Lynch, Joseph W. (2014) The impact of human hyperekplexia mutations on glycine receptor structure and function. Molecular Brain7 2: 1-12. doi:10.1186/1756-6606-7-2

Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery

Talwar, Sahil and Lynch, Joseph W. (2014) Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery. International Journal of Biochemistry and Cell Biology53 218-233. doi:10.1016/j.biocel.2014.05.028

Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation

Bode, Anna and Lynch, Joseph W. (2013) Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation. Journal of Biological Chemistry288 47: 33760-33771. doi:10.1074/jbc.M113.513804

New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms

Bode, Anna, Wood, Sian-Elin, Mullins, Jonathan G. L., Keramidas, Angelo, Cushion, Thomas D., Thomas, Rhys H., Pickrell, William O., Drew, Cheney J. G., Masri, Amira, Jones, Elizabeth A., Vassallo, Grace, Born, Alfred P., Alehan, Fusun, Aharoni, Sharon, Bannasch, Gerald, Bartsch, Marius, Kara, Bulent, Krause, Amanda, Karam, Elie G., Matta, Stephanie, Jain, Vivek, Mandel, Hanna, Freilinger, Michael, Graham, Gail E., Hobson, Emma, Chatfield, Sue, Vincent-Delorme, Catherine, Rahme, Jubran E., Afawi, Zaid, Berkovic, Samuel F., Howell, Owain W., Vanbellinghen, Jean-Francois, Rees, Mark I., Chung, Seo-Kyung and Lynch, Joseph W. (2013) New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms. Journal of Biological Chemistry288 47: 33745-33759. doi:10.1074/jbc.M113.509240

Phosphorylation of α3 glycine receptors induces a conformational change in the glycine-binding site

Han, Lu, Talwar, Sahil, Wang, Qian, Shan, Qiang and Lynch, Joseph W. (2013) Phosphorylation of α3 glycine receptors induces a conformational change in the glycine-binding site. ACS Chemical Neuroscience4 10: 1361-1370. doi:10.1021/cn400097j

Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia

Balansa, Walter, Islam, Robiul, Fontaine, Frank, Piggott, Andrew M., Zhang, Hua, Xiao, Xue, Webb, Timothy I., Gilbert, Daniel F., Lynch, Joseph W. and Capon, Robert J. (2013) Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia. Organic and Biomolecular Chemistry11 28: 4695-4701. doi:10.1039/c3ob40861b

Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator

Balansa, Walter, Islam, Robiul, Gilbert, Daniel F., Fontaine, Frank, Xiao, Xue, Zhang, Hua, Piggott, Andrew M., Lynch, Joseph W. and Capon, Robert J. (2013) Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator. Bioorganic and Medicinal Chemistry21 14: 4420-4425. doi:10.1016/j.bmc.2013.04.061

Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease

James, Victoria M., Bode, Anna, Chung, Seo-Kyung, Gill, Jennifer L., Nielsen, Maartje, Cowan, Frances M., Vujic, Mihailo, Thomas, Rhys H., Rees, Mark I., Harvey, Kirsten, Keramidas, Angelo, Topf, Maya, Ginjaar, Ieke, Lynch, Joseph W. and Harvey, Robert J. (2013) Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease. Neurobiology of Disease52 137-149. doi:10.1016/j.nbd.2012.12.001

Fluorescence-based high-throughput functional profiling of ligand-gated ion channels at the level of single cells

Talwar, Sahil, Lynch, Joseph W. and Gilbert, Daniel F. (2013) Fluorescence-based high-throughput functional profiling of ligand-gated ion channels at the level of single cells. PLoS One8 3: e58479.1-e58479.11. doi:10.1371/journal.pone.0058479

GLRB is the third major gene of effect in hyperekplexia

Chung, Seo-Kyung, Bode, Anna, Cushion, Thomas D., Thomas, Rhys H., Hunt, Charlotte, Wood, Sian-Elin, Pickrell, William O., Drew, Cheney J. G., Yamashita, Sumimasa, Shiang, Rita, Leiz, Steffen, Longhardt, Ann-Carolyn, Raile, Vera, Weschke, Bernhard, Puri, Ratna D., Verma, Ishwar C., Harvey, Robert J., Ratnasinghe, Didi D., Parker, Michael, Rittey, Chris, Masri, Amira, Lingappa, Lokesh, Howell, Owain W., Vanbellinghen, Jean-François, Mullins, Jonathan G., Lynch, Joseph W. and Rees, Mark I. (2013) GLRB is the third major gene of effect in hyperekplexia. Human Molecular Genetics22 5: 927-940. doi:10.1093/hmg/dds498

The relative orientation of the TM3 and TM4 domains varies between α1 and α3 glycine receptors

Han, Lu, Talwar, Sahil and Lynch, Joseph W. (2013) The relative orientation of the TM3 and TM4 domains varies between α1 and α3 glycine receptors. ACS Chemical Neuroscience4 2: 248-254. doi:10.1021/cn300177g

An outline of desensitization in pentameric ligand-gated ion channel receptors

Keramidas, Angelo and Lynch, Joseph W. (2012) An outline of desensitization in pentameric ligand-gated ion channel receptors. Cellular and Molecular Life Sciences70 7: 1241-1253. doi:10.1007/s00018-012-1133-z

Ivermectin binding sites in human and invertebrate Cys-loop receptors

Lynagh, Timothy and Lynch, Joseph W. (2012) Ivermectin binding sites in human and invertebrate Cys-loop receptors. Trends in Pharmacological Sciences33 8: 432-441. doi:10.1016/j.tips.2012.05.002

Stoichiometry and subunit arrangement of alpha 1 beta glycine receptors as determined by atomic force microscopy

Yang, Zhe, Taran, Elena, Webb, Timothy I. and Lynch, Joseph W. (2012) Stoichiometry and subunit arrangement of alpha 1 beta glycine receptors as determined by atomic force microscopy. Biochemistry51 26: 5229-5231. doi:10.1021/bi300063m

Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin

Timothy Lynagh and Lynch, Joseph W. (2012) Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin. Frontiers in Molecular Neuroscience5 60.1-60.11. doi:10.3389/fnmol.2012.00060

Distinct properties of glycine receptor β+/α- interface: Unambiguously characterizing heteromeric interface reconstituted in homomeric protein

Shan, Qiang, Han, Lu and Lynch, Joseph W. (2012) Distinct properties of glycine receptor β+/α- interface: Unambiguously characterizing heteromeric interface reconstituted in homomeric protein. Journal of Biological Chemistry287 25: 21244-21252. doi:10.1074/jbc.M111.337741

Function of hyperekplexia-causing alpha(1)R271Q/L glycine receptors is restored by shifting the affected residue out of the allosteric signaling pathway

Shan, Qiang, Han, Lu and Lynch, Joseph W. (2012) Function of hyperekplexia-causing alpha(1)R271Q/L glycine receptors is restored by shifting the affected residue out of the allosteric signaling pathway. British Journal of Pharmacology165 7: 2113-2123. doi:10.1111/j.1476-5381.2011.01701.x

Mechanism of action of the insecticides, lindane and fipronil, on glycine receptor chloride channels

Islam, Robiul and Lynch, Joseph W. (2012) Mechanism of action of the insecticides, lindane and fipronil, on glycine receptor chloride channels. British Journal of Pharmacology165 8: 2707-2720. doi:10.1111/j.1476-5381.2011.01722.x

Incompatibility between a pair of residues from the Pre-M1 linker and Cys-loop blocks surface expression of the Glycine Receptor

Shan, Qiang and Lynch, Joseph W. (2012) Incompatibility between a pair of residues from the Pre-M1 linker and Cys-loop blocks surface expression of the Glycine Receptor. Journal of Biological Chemistry287 10: 7535-7542. doi:10.1074/jbc.M111.325126

A comparison of glycine-and ivermectin-mediated conformational changes in the glycine receptor ligand-binding domain

Wang, Qian and Lynch, Joseph W. (2012) A comparison of glycine-and ivermectin-mediated conformational changes in the glycine receptor ligand-binding domain. International Journal of Biochemistry and Cell Biology44 2: 335-340. doi:10.1016/j.biocel.2011.11.005

Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channel

Lynagh, Timothy, Webb, Timothy I., Dixon, Christine L., Cromer, Brett A. and Lynch, Joseph W. (2011) Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channel. Journal of Biological Chemistry286 51: 43913-43924. doi:10.1074/jbc.M111.262634

Beta subunit M2-M3 loop conformational changes are uncoupled from alpha1 beta glycine receptor channel gating: Implications for human hereditary hyperekplexia

Shan, Qiang, Han, Lu and Lynch, Joseph W. (2011) Beta subunit M2-M3 loop conformational changes are uncoupled from alpha1 beta glycine receptor channel gating: Implications for human hereditary hyperekplexia. PLoS One6 11: e28105.1-e28105.11. doi:10.1371/journal.pone.0028105

Activation and desensitization induce distinct conformational changes at the extracellular-transmembrane domain interface of the glycine receptor

Wang, Qian and Lynch, Joseph W. (2011) Activation and desensitization induce distinct conformational changes at the extracellular-transmembrane domain interface of the glycine receptor. Journal of Biological Chemistry286 44: 38814-38824. doi:10.1074/jbc.M111.273631

A cation-π interaction at a phenylalanine residue in the glycine receptor binding site is conserved for different agonists

Pless, Stephan A., Hanek, Ariele P., Price, Kerry L., Lynch, Joseph W., Lester, Henry A., Dougherty, Dennis A. and Lummis, Sarah C. R. (2011) A cation-π interaction at a phenylalanine residue in the glycine receptor binding site is conserved for different agonists. Molecular Pharmacology79 4: 742-748. doi:10.1124/mol.110.069583

Ligand- and subunit-specific conformational changes in the ligand-binding domain and the TM2-TM3 linker of α1 β2 γ2 GABAA receptors

Wang, Qian, Pless, Stephan A. and Lynch, Joseph W. (2010) Ligand- and subunit-specific conformational changes in the ligand-binding domain and the TM2-TM3 linker of α1 β2 γ2 GABAA receptors. Journal of Biological Chemistry285 51: 40373-40386. doi:10.1074/jbc.M110.161513

A glycine residue essential for high ivermectin sensitivity in Cys-loop ion channel receptors

Lynagh, Timothy and Lynch, Joseph W. (2010) A glycine residue essential for high ivermectin sensitivity in Cys-loop ion channel receptors. International Journal for Parasitology40 13: 1477-1481. doi:10.1016/j.ijpara.2010.07.010

Chimera construction using multiple-template-based sequential PCRs

Shan, Qiang and Lynch, Joseph W. (2010) Chimera construction using multiple-template-based sequential PCRs.Journal of Neuroscience Methods193 1: 86-89. doi:10.1016/j.jneumeth.2010.08.033

Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2

Gebhardt, FM, Mitrovic, AD, Gilbert, DF, Vandenberg, RJ, Lynch, JW and Dodd, PR (2010) Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2. Journal of Biological Chemistry285 41: 31313-31324. doi:10.1074/jbc.M110.153494

Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia

Chung, Seo-Kyung, Vanbellinghen, Jean-Francois, Mullins, Jonathan G. L., Robinson, Angela, Hantke, Janina, Hammond, Carrie L., Gilbert, Daniel F., Freilinger, Michael, Ryan, Monique, Kruer, Michael C., Masri, Amira, Gurses, Candan, Ferrie, Colin, Harvey, Kirsten, Shiang, Rita, Christodoulou, John, Andermann, Frederick, Andermann, Eva, Thomas, Rhy H., Harvey, Robert J., Lynch, Joseph W. and Rees, Mark I. (2010) Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia. Journal of Neuroscience30 28: 9612-9620. doi:10.1523/JNEUROSCI.1763-10.2010

An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populations

Lynagh, Timothy and Lynch, Joseph W. (2010) An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populations. Journal of Biological Chemistry285 20: 14890-14897. doi:10.1074/jbc.M110.107789

Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae

Balansa, Walter, Islam, Robiul, Fontaine, Frank, Piggott, Andrew M., Zhang, Hua, Webb, Timothy I., Gilbert, Daniel F., Lynch, Joseph W. and Capon, Robert J. (2010) Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae. Bioorganic and Medicinal Chemistry18 8: 2912-2919. doi:10.1016/j.bmc.2010.03.002

Differential expression of glycine receptor subunits in the rat basolateral and central amygdala

Delaney, A. J., Esmaeili, A., Sedlak, Petra L., Lynch, J. W. and Sah, P. (2010) Differential expression of glycine receptor subunits in the rat basolateral and central amygdala. Neuroscience Letters469 2: 237-242. doi:10.1016/j.neulet.2009.12.003

Magnitude of a conformational change in the glycine receptor β1- β2 loop is correlated with agonist efficacy

Pless, Stephan A. and Lynch, Joseph W. (2009) Magnitude of a conformational change in the glycine receptor β1- β2 loop is correlated with agonist efficacy. The Journal of Biological Chemistry284 40: 27370-27376. doi:10.1074/jbc.M109.048405

Molecular determinants of β-carboline inhibition of the glycine receptor

Chen, Xuebin, Cromer, Brett. A. and Lynch, Joseph W. (2009) Molecular determinants of β-carboline inhibition of the glycine receptor. Journal Of Neurochemistry110 5: 1685-1694. doi:10.1111/j.1471-4159.2009.06273.x

The M4 transmembrane segment contributes to agonist efficacy differences between alpha1 and alpha3 glycine receptors

Chen, Xuebin, Webb, Timothy I. and Lynch, Joseph W. (2009) The M4 transmembrane segment contributes to agonist efficacy differences between alpha1 and alpha3 glycine receptors. Molecular Membrane Biology26 5-7: 321-332. doi:10.1080/09687680903120319

Ligand-specific conformational changes in the α1 glycine receptor ligand-binding domain

Pless, Stephan A. and Lynch, Joseph W. (2009) Ligand-specific conformational changes in the α1 glycine receptor ligand-binding domain. The Journal of Biological Chemistry284 23: 15847-15856. doi:10.1074/jbc.M809343200

Multiplexed labeling of viable cells for high-throughput analysis of glycine receptor function using flow cytometry

Gilbert, Daniel, Wilson, John C., Nink, Virginia, Lynch, Joseph W. and Osborne, Geoffrey W. (2009) Multiplexed labeling of viable cells for high-throughput analysis of glycine receptor function using flow cytometry. Cytometry Part A75A 5: 440-449. doi:10.1002/cyto.a.20703

Dihydropyridine inhibition of the glycine receptor: Subunit selectivity and a molecular determinant of inhibition

Chen, Xuebin, Cromer, Brett, Webb, Timothy I., Yang, Zhe, Hantke, Janina, Harvey, Robert J., Parker, Michael W. and Lynch, Joseph W. (2009) Dihydropyridine inhibition of the glycine receptor: Subunit selectivity and a molecular determinant of inhibition. Neuropharmacology56 1: 318-327. doi:10.1016/j.neuropharm.2008.07.001

Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits

Pless, Stephan and Lynch, Joseph W. (2009) Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits. Journal Of Neurochemistry108 6: 1585-1594. doi:10.1111/j.1471-4159.2009.05930.x

GABAᴀ receptors containing gamma 1 subunits contribute to inhibitory transmission in the central amygdala

Esmaeili, Abolghasem, Lynch, Joseph W. and Sah, Pankaj (2009) GABAᴀ receptors containing gamma 1 subunits contribute to inhibitory transmission in the central amygdala. Journal of Neurophysiology101 1: 341-349. doi:10.1152/jn.90991.2008

High throughput techniques for discovering new glycine receptor modulators and their binding sites

Gilbert, Daniel, Islam, Robiul, Lynagh, Timothy, Lynch, Joseph W. and Webb, Timothy I. (2009) High throughput techniques for discovering new glycine receptor modulators and their binding sites. Frontiers in Molecular Neuroscience2 OCT: 1-10. doi:10.3389/neuro.02.017.2009

Native glycine receptor subtypes and their physiological roles

Lynch, Joseph W. (2009) Native glycine receptor subtypes and their physiological roles. Neuropharmacology56 1: 303-309. doi:10.1016/j.neuropharm.2008.07.034

Optimizing the expression of recombinant αβγ GABAA receptors in HEK293 cells for high-throughput screening

Gilbert, Daniel, Esmaeili, Abolghasem and Lynch, Joseph W. (2009) Optimizing the expression of recombinant αβγ GABAA receptors in HEK293 cells for high-throughput screening. Journal of Biomolecular Screening14 1: 86-91. doi:10.1177/1087057108328017

A Cation-π Interaction in the Binding Site of the Glycine Receptor Is Mediated by a Phenylalanine Residue

Pless, Stephan A., Millen, Kat S., Hanek, Ariele P., Lynch, Joseph W., Lester, Henry A., Lummis, Sarah C. R. and Dougherty, Dennis A. (2008) A Cation-π Interaction in the Binding Site of the Glycine Receptor Is Mediated by a Phenylalanine Residue. Journal of Neuroscience28 43: 10937-10942. doi:10.1523/JNEUROSCI.2540-08.2008

Subunit-specific modulation of glycine receptors by cannabinoids and N-arachidonyl-glycine

Yang, Zhe, Aubrey, Karin R., Alroy, Iris, Harvey, Robert J., Vandenberg, Robert J. and Lynch, Joseph W. (2008) Subunit-specific modulation of glycine receptors by cannabinoids and N-arachidonyl-glycine. Biochemical Pharmacology76 8: 1014-1023. doi:10.1016/j.bcp.2008.07.037

Illuminating the structure and function of Cys-loop receptors

Pless, Stephan A and Lynch, Joseph W (2008) Illuminating the structure and function of Cys-loop receptors. Clinical And Experimental Pharmacology And Physiology35 10: 1137-1142. doi:10.1111/j.1440-1681.2008.04954.x

Subunit-specitic potentiation of recombinant glycine receptors by NV-31, a bilobalide-derived compound

Lynch, Joseph W. and Chen, Xuebin (2008) Subunit-specitic potentiation of recombinant glycine receptors by NV-31, a bilobalide-derived compound. Neuroscience letters435 2: 147-151. doi:10.1016/j.neulet.2008.02.022

Structure-activity analysis of ginkgolide binding in the glycine receptor pore

Heads, J. A., Hawthorne, R. L., Lynagh, T. and Lynch, J. W. (2008) Structure-activity analysis of ginkgolide binding in the glycine receptor pore. Journal of Neurochemistry105 4: 1418-1427. doi:10.1111/j.1471-4159.2008.05244.x

Tropisetron modulation of the glycine receptor: femtomolar potentiation and a molecular determinant of inhibition

Yang, Zhe, Ney, Agnieszka, Cromer, Brett A., Ng, Hooi-Ling, Parker, Michael W. and Lynch, Joseph W. (2007) Tropisetron modulation of the glycine receptor: femtomolar potentiation and a molecular determinant of inhibition.Journal of Neurochemistry100 3: 758-769. doi:10.1111/j.1471-4159.2006.04242.x

A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore

Yang, Zhe, Cromer, Brett A., Harvey, Robert J., Parker, Michael W. and Lynch, Joseph W. (2007) A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Journal of Neurochemistry103 2: 580-589. doi:10.1111/j.1471-4159.2007.04850.x

Closed-state cross-linking of adjacent beta 1 Subunits in alpha 1 beta 1 GABA(a) receptors via introduced 6 ' cysteines

Yang, Zhe, Webb, Timothy I. and Lynch, Joseph W. (2007) Closed-state cross-linking of adjacent beta 1 Subunits in alpha 1 beta 1 GABA(a) receptors via introduced 6 ' cysteines. Journal of Biological Chemistry282 23: 16803-16810. doi:10.1074/jbc.M611555200

Conformational variability of the glycine receptor M2 domain in response to activation by different agonists

Pless, Stephen A., Dibas, Mohammed I., Lester, Henry A. and Lynch, Joseph W. (2007) Conformational variability of the glycine receptor M2 domain in response to activation by different agonists. Journal of Biological Chemistry282 49: 36057-36067. doi:10.1074/jbc.M706468200

Molecular pharmacology of the glycine receptor chloride channel

Webb, TI and Lynch, JW (2007) Molecular pharmacology of the glycine receptor chloride channel. Current Pharmaceutical Design13 23: 2350-2367. doi:10.2174/138161207781368693

Glycine receptors: A new therapeutic target in pain pathways

Lynch, JW and Callister, RJ (2006) Glycine receptors: A new therapeutic target in pain pathways. Current Opinion In Investigational Drugs7 1: 48-53.

High-throughput screening of glycine and GAB(A)A receptors: Why and how?

Lynch, J. W. (2006) High-throughput screening of glycine and GAB(A)A receptors: Why and how?. Alcoholism-Clinical And Experimental Research30 9: 61A-61A.

Molecular determinants of ginkgolide binding in the glycine receptor pore

Hawthorne, R., Cromer, B. A., Ng, H. L., Parker, M. W. and Lynch, J. W. (2006) Molecular determinants of ginkgolide binding in the glycine receptor pore. Journal of Neurochemistry98 2: 395-407. doi:10.1111/j.1471-4159.2006.03875.x

A yellow fluorescent protein-based assay for high-throughput screening of glycine and GABA(A) receptor chloride channels

Kruger, Wade, Gilbert, Daniel, Hawthorne, Rebecca, Hryciw, Deanne H., Frings, Stephan, Poronnik, Philip and Lynch, Joseph W. (2005) A yellow fluorescent protein-based assay for high-throughput screening of glycine and GABA(A) receptor chloride channels. Neuroscience Letters380 3: 340-345. doi:10.1016/j.neulet.2005.01.065

A picrotoxin-specific conformational change in the glycine receptor M2-M3 loop.

Hawthorne, Rebecca L. and Lynch, Joseph W. (2005) A picrotoxin-specific conformational change in the glycine receptor M2-M3 loop.. Journal of Biological Chemistry280 43: 35836-35843. doi:10.1074/jbc.M506645200

High throughput screening of neuronal Cl- channels: Why and how?

Lynch, J. W. (2005) High throughput screening of neuronal Cl- channels: Why and how?. Current Neuropharmacology3 4: 207-216. doi:10.2174/1570159054368286

Ligand-gated channels

Barry, P. H. and Lynch, J. W. (2005) Ligand-gated channels. Ieee Transactions On Nanobioscience4 1: 70-80. doi:10.1109/TNB.2004.842497

Molecular structure and function of the glycine receptor chloride channel

Lynch, J. W. (2004) Molecular structure and function of the glycine receptor chloride channel. Physiological Reviews,84 4: 1051-1095. doi:10.1152/physrev.00042.2003

Comparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptor

Han, N. L. R., Clements, J. D. and Lynch, J. W. (2004) Comparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptor. Journal of Biological Chemistry279 19: 19559-19565. doi:10.1074/jbc.M400548200

Asymmetric contribution of α and β subunits to the activation of αβ heteromeric glycine receptors

Shan, Q., Nevin, S. T., Haddrill, J. L. and Lynch, J. W. (2003) Asymmetric contribution of α and β subunits to the activation of αβ heteromeric glycine receptors. Journal of Neurochemistry86 2: 498-507. doi:10.1046/j.1471-4159.2003.01872.x

Insights into the structural basis for zinc inhibition of the glycine receptor

Nevin, S. T., Cromer, B. A., Haddrill, J. L., Morton, C. J., Parker, M. W. and Lynch, J. W. (2003) Insights into the structural basis for zinc inhibition of the glycine receptor. Journal of Biological Chemistry278 31 August 1: 28985-28992. doi:10.1074/jbc.M300097200

Comparative surface accessibility of a pore-lining threonine residue (T6') in the glycine and GABA(A) receptors

Shan, Qiang, Haddrill, Justine L. and Lynch, Joseph W. (2002) Comparative surface accessibility of a pore-lining threonine residue (T6') in the glycine and GABA(A) receptors. Journal of Biological Chemistry277 47: 44845-44853. doi:10.1074/jbc.M208647200

Effects of polyunsaturated fatty acids on voltage-gated K+ and Na+ channels in rat olfactory receptor neurons

Seebungkert, B. and Lynch, J. W. (2002) Effects of polyunsaturated fatty acids on voltage-gated K+ and Na+ channels in rat olfactory receptor neurons. European Journal of Neuroscience16 8: 2085-2094. doi:10.1046/j.1460-9568.2002.02288.x

Characterization of a glycine receptor domain that controls the binding and gating mechanisms of the beta-amino acid agonist, taurine

Han, Nian-Lin R., Haddrill, Justine L. and Lynch, Joseph W. (2001) Characterization of a glycine receptor domain that controls the binding and gating mechanisms of the beta-amino acid agonist, taurine. Journal of Neurochemistry79 3: 636-647. doi:10.1046/j.1471-4159.2001.00601.x

Ivermectin, an unconventional agonist of the glycine receptor chloride channel

Shan, Q., Haddrill, J. L. and Lynch, J. W. (2001) Ivermectin, an unconventional agonist of the glycine receptor chloride channel. Journal of Biological Chemistry276 16: 12556-12564. doi:10.1074/jbc.M011264200

A common inhibitory binding site for zinc and odorants at the voltage-gated K+ channel of rat olfactory receptor neurons

Seebungkert, B and Lynch, JW (2001) A common inhibitory binding site for zinc and odorants at the voltage-gated K+ channel of rat olfactory receptor neurons. European Journal of Neuroscience14 2: 353-362. doi:10.1046/j.0953-816x.2001.01646.x

A single beta subunit M2 domain residue controls the picrotoxin sensitivity of alpha beta heteromeric glycine receptor chloride channels

Shan, Q., Haddrill, J. L. and Lynch, J. W. (2001) A single beta subunit M2 domain residue controls the picrotoxin sensitivity of alpha beta heteromeric glycine receptor chloride channels. Journal of Neurochemistry76 4: 1109-1120. doi:10.1046/j.1471-4159.2001.00124.x

The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state

Lynch, J. W., Han, N. L. R., Haddrill, J., Pierce, K. D. and Schofield, P. R. (2001) The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state. Journal of Neuroscience21 8: 2589-2599.

A pore-lining glutamic acid in the rat olfactory cyclic nucleotide-gated channel controls external spermine block

Nevin, Simon T., Haddrill, Justine L. and Lynch, Joseph W. (2000) A pore-lining glutamic acid in the rat olfactory cyclic nucleotide-gated channel controls external spermine block. Neuroscience Letters296 2-3: 163-167. doi:10.1016/S0304-3940(00)01650-5

Rectification of the olfactory cyclic nucleotide-gated channel by intracellular polyamines

Lynch, J. W. (1999) Rectification of the olfactory cyclic nucleotide-gated channel by intracellular polyamines. Journal of Membrane Biology170 3: 213-227. doi:10.1007/s002329900551

Identification of a new ligand binding domain in the al subunit of the inhibitory glycine receptor

Vafa, B, Lewis, TM, Cunningham, AM, Jacques, P, Lynch, JW and Schofield, PR (1999) Identification of a new ligand binding domain in the al subunit of the inhibitory glycine receptor. Journal of Neurochemistry73 5: 2158-2166.

Characterization of calcium-activated chloride channels in patches excised from the dendritic knob of mammalian olfactory receptor neurons

Hallani, M, Lynch, JW and Barry, PH (1998) Characterization of calcium-activated chloride channels in patches excised from the dendritic knob of mammalian olfactory receptor neurons. Journal of Membrane Biology161 2: 163-171. doi:10.1007/s002329900323

Nitric oxide inhibition of the rat olfactory cyclic nucleotide-gated cation channel

Lynch, JW (1998) Nitric oxide inhibition of the rat olfactory cyclic nucleotide-gated cation channel. Journal of Membrane Biology165 3: 227-234. doi:10.1007/s002329900436

Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways

Lynch, JW, Jacques, P, Pierce, KD and Schofield, PR (1998) Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways. Journal of Neurochemistry71 5: 2159-2168.

Concentration dependence of sodium permeation and sodium ion interactions in the cyclic AMP-gated channels of mammalian olfactory receptor neurons

Balasubramanian, S, Lynch, JW and Barry, PH (1997) Concentration dependence of sodium permeation and sodium ion interactions in the cyclic AMP-gated channels of mammalian olfactory receptor neurons. Journal of Membrane Biology159 1: 41-52. doi:10.1007/s002329900267

Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel

Lynch, JW, Rajendra, S, Pierce, KD, Handford, CA, Barry, PH and Schofield, PR (1997) Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel. Embo Journal16 1: 110-120. doi:10.1093/emboj/16.1.110

Odorant-induced currents in intact patches from rat olfactory receptor neurons: Theory and experiment

Chiu, P, Lynch, JW and Barry, PH (1997) Odorant-induced currents in intact patches from rat olfactory receptor neurons: Theory and experiment. Biophysical Journal72 3: 1442-1457.

The glycine receptor

Rajendra, S, Lynch, JW and Schofield, PR (1997) The glycine receptor. Pharmacology & Therapeutics73 2: 121-146. doi:10.1016/S0163-7258(96)00163-5

Calcium-dependent modulation of the agonist affinity of the mammalian olfactory cyclic nucleotide-gated channel by calmodulin and a novel endogenous factor

Balasubramanian, S, Lynch, JW and Barry, PH (1996) Calcium-dependent modulation of the agonist affinity of the mammalian olfactory cyclic nucleotide-gated channel by calmodulin and a novel endogenous factor. Journal of Membrane Biology152 1: 13-23. doi:10.1007/s002329900081

Molecular and genetic insights into ligand binding and signal transduction at the inhibitory glycine receptor

Schofield, PR, Lynch, JW, Rajendra, S, Pierce, KD, Handford, CA and Barry, PH (1996) Molecular and genetic insights into ligand binding and signal transduction at the inhibitory glycine receptor. Cold Spring Harbor Symposia On Quantitative Biology61 333-342.

The human glycine receptor beta subunit: Primary structure, functional characterisation and chromosomal localisation of the human and murine genes

Handford, CA, Lynch, JW, Baker, E, Webb, GC, Ford, JH, Sutherland, GR and Schofield, PR (1996) The human glycine receptor beta subunit: Primary structure, functional characterisation and chromosomal localisation of the human and murine genes. Molecular Brain Research35 1-2: 211-219.

The Permeation of Organic Cations Through Camp-Gated Channels in Mammalian Olfactory Receptor Neurons

Balasubramanian, S, Lynch, JW and Barry, PH (1995) The Permeation of Organic Cations Through Camp-Gated Channels in Mammalian Olfactory Receptor Neurons. Journal of Membrane Biology146 2: 177-191.

Mutations affecting the glycine receptor agonist transduction mechanism convert the competitive antagonist, picrotoxin, into an allosteric potentiator

Lynch, Joseph W., Rajendra, Sundran, Barry, Peter H. and Schofield, Peter R. (1995) Mutations affecting the glycine receptor agonist transduction mechanism convert the competitive antagonist, picrotoxin, into an allosteric potentiator. Journal of Biological Chemistry270 23: 13799-13806. doi:10.1074/jbc.270.23.13799

Mutation of An Arginine Residue in the Human Glycine Receptor Transforms Beta-Alanine and Taurine From Agonists Into Competitive Antagonists

Rajendra, S, Lynch, JW, Pierce, KD, French, CR, Barry, PH and Schofield, PR (1995) Mutation of An Arginine Residue in the Human Glycine Receptor Transforms Beta-Alanine and Taurine From Agonists Into Competitive Antagonists.Neuron14 1: 169-175. doi:10.1016/0896-6273(95)90251-1

Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor

Rajendra, Sundran, Lynch, Joseph W., Pierce, Kerrie D., French, Chris R., Barry, Peter H. and Schofield, Peter R. (1994) Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor. Journal of Biological Chemistry269 29: 18739-18742.

A Missense Mutation in the Gene Encoding the Alpha(1) Subunit of the Inhibitory Glycine Receptor in the Spasmodic Mouse

Ryan, SG, Buckwalter, MS, Lynch, JW, Handford, CA, Segura, L, Shiang, R, Wasmuth, JJ, Camper, SA, Schofield, P and Oconnell, P (1994) A Missense Mutation in the Gene Encoding the Alpha(1) Subunit of the Inhibitory Glycine Receptor in the Spasmodic Mouse. Nature Genetics7 2: 131-135. doi:10.1038/ng0694-131

A pertussis toxin-insensitive calcium influx mediated by neuropeptide Y2 receptors in a human neuroblastoma cell line

Lynch, Joseph W., Lemos, Virginia Soar, Bucher, Bernard, Stoclet, Jean-Claude and Takeda, Kenneth (1994) A pertussis toxin-insensitive calcium influx mediated by neuropeptide Y2 receptors in a human neuroblastoma cell line.Journal of Biological Chemistry269 11: 8226-8233.

Cyclic Nucleotide-Gated Channels of Rat Olfactory Receptor-Cells - Divalent-Cations Control the Sensitivity to Camp

Lynch, JW and Lindemann, B (1994) Cyclic Nucleotide-Gated Channels of Rat Olfactory Receptor-Cells - Divalent-Cations Control the Sensitivity to Camp. Journal of General Physiology103 1: 87-106. doi:10.1085/jgp.103.1.87

Properties of Cyclic-Nucleotide Gated Channels Mediating Olfactory Transduction - Activation, Selectivity, and Blockage

Frings, S, Lynch, JW and Lindemann, B (1992) Properties of Cyclic-Nucleotide Gated Channels Mediating Olfactory Transduction - Activation, Selectivity, and Blockage. Journal of General Physiology100 1: 45-67. doi:10.1085/jgp.100.1.45

An Analysis of Na+ Currents in Rat Olfactory Receptor Neurons

Rajendra, S, Lynch, JW and Barry, PH (1992) An Analysis of Na+ Currents in Rat Olfactory Receptor Neurons.Pflugers Archiv-European Journal of Physiology420 3-4: 342-346. doi:10.1007/BF00374468

Slowly Activating K+ Channels in Rat Olfactory Receptor Neurons

Lynch, JW and Barry, PH (1991) Slowly Activating K+ Channels in Rat Olfactory Receptor Neurons. Proceedings of the Royal Society B-Biological Sciences244 1311: 219-225. doi:10.1098/rspb.1991.0074

Properties of Transient K+ Currents and Underlying Single K+ Channels in Rat Olfactory Receptor Neurons

Lynch, JW and Barry, PH (1991) Properties of Transient K+ Currents and Underlying Single K+ Channels in Rat Olfactory Receptor Neurons. Journal of General Physiology97 5: 1043-1072. doi:10.1085/jgp.97.5.1043

Liquid Junction Potentials and Small-Cell Effects in Patch-Clamp Analysis

Barry, PH and Lynch, JW (1991) Liquid Junction Potentials and Small-Cell Effects in Patch-Clamp Analysis. Journal of Membrane Biology121 2: 101-117. doi:10.1007/BF01870526

Inward Rectification in Rat Olfactory Receptor Neurons

Lynch, JW and Barry, PH (1991) Inward Rectification in Rat Olfactory Receptor Neurons. Proceedings of the Royal Society B-Biological Sciences243 1307: 149-153. doi:10.1098/rspb.1991.0024

Action-Potentials Initiated by Single Channels Opening in a Small Neuron (Rat Olfactory Receptor)

Lynch, JW and Barry, PH (1989) Action-Potentials Initiated by Single Channels Opening in a Small Neuron (Rat Olfactory Receptor). Biophysical Journal55 4: 755-768.

A Temperature and Solution Control-System for the Measurement of Single Channel Currents in Excised Membrane Patches

Lynch, JW, Barry, PH and Quartararo, N (1988) A Temperature and Solution Control-System for the Measurement of Single Channel Currents in Excised Membrane Patches. Pflugers Archiv-European Journal of Physiology412 3: 322-327. doi:10.1007/BF00582515

 

  • Brett Cromer, RMIT University
  • Pankaj Sah, The University of Queensland
  • Rob Capon, The University of Queensland
  • Mark Rees, University of Swansea
  • Seo-kyung Chung, University of Swansea
  • Daniel Gilbert, University of Erlangen
  • Robert Harvey, London School of Pharmacy
  • Chris Ulens, KU Leuven
  • Andrew Jenkins, Emory University

 

 

Project 1:  Investigating the mechanism by which hereditary mutations to the potassium/chloride co-transporter, KCC2, cause epilepsy.

 

Project 2:  Discovering new drugs that control malaria-transmitting Anopheles mosquitos by targeting their glutamate-gated chloride channels.

Project 3:  Discovering new drugs for treating chronic inflammatory pain by targeting alpha3 glycine receptors.

Project 4:  Molecular mechanisms regulating synaptic clustering of alpha5-containing GABA-A receptors.

How to apply