Title: Conotoxins, ion channels and pain

Speaker: David J. Adams. Ph.D. (Professor, Director, Health Innovations Research Institute, RMIT University, Australia)

Time: July 02 2015, Thursday, 10am

Venue: KIZ main building, conference room 327 

Everyone is welcomed!

Research interest of Prof Adams:

The primary areas of research interest in the laboratory of Professor Adams are in neuroscience and membrane physiology using electrophysiological, molecular biological and fluorescence imaging techniques to study membrane receptors and ionic channels and calcium signalling.

Research in the laboratory focuses on:

1. the expression, function and modulation of native receptors and ionic channels in sensory neurons, and
2. the molecular mechanisms of action of venom peptides on cloned receptors and ion channels expressed in Xenopus oocytes and transfected mammalian cell lines.

Specifically, the laboratory investigates conotoxins that selectively modulate receptor and ion channel function and the ionic mechanisms underlying neuronal excitability in sensory neurons using patch clamp recording techniques.

Selected recent publications:

• Berecki G, McArthur JR, Cuny H, Clark RJ and Adams DJ (2014). Differential Cav2.1 and Cav2.3 channel inhibition by baclofen and alpha-conotoxin Vc1.1 via GABAB receptor activation. The Journal of General Physiology 143(4) 465-479.
• Berecki G, Daly NL, Huang YH, Vink S, Craik DJ, Alewood PF and Adams DJ (2014). Effects of arginine 10 to lysine substitution on omega-conotoxin CVIE and CVIF block of Cav2.2 channels. British Journal of Pharmacology171 3313-3327.
• Yasuda, T., Cuny, H. and Adams, D.J. (2013). Kv3.1 channels stimulate adult neural precursor cell proliferation and neuronal differentiation. Journal of Physiology (Lond.)591, 2579-2591.
• Adams, D.J. and Berecki, G. (2013) Mechanisms of conotoxin inhibition of N-type (Cav2.2) calcium channels. Biochem Biophys Acta – Biomembranes1828, 1619-1628
• Van Lierop, B.J., Robinson, S. D., Kompella, S. N., Belgi, A., McArthur, J. R., Hung, A., MacRaild, C.A., Adams, D.J., Norton, R.S., and Robinson A.J. (2013). Dicarba α-Conotoxin Vc1.1 analgogues with differential selectivity for nicotinic acetycholine and GABAB receptors. ACS Chemical Biology 8, 1815-1821.
• 3β4 Nicotinic acetylcholine receptors.aGrishin, A. A., Cuny, H., Hung, A., Clark, R.J., Brust, A., Akondi, K., Alewood, P., Craik, D.J. and Adams, D.J. (2013) Identifying key amino acid residues that affect α-conotoxin AuIB inhibition of  Journal of Biological Chemistry288(48), 34428-34442.
• Kabbani, N., Nordman, J.C., Corgiat, B.A., Veltri, D.P., Shehu, A., Seymour, V.A., Adams, D.J. (2013). Are nicotinic acetylcholine receptors coupled to G proteins? Bioessays-journal35: 1025-1034.
• Cuny H, de Faoite A, Huynh T, Yasuda T, Berecki G and Adams DJ. (2012). γ – Aminobutyric acid type B (GABA_B) receptor expression needed for inhibition of N-type (Ca_v2.2) calcium channels by analgesic α-conotoxins. Journal of Biological Chemistry287, 23948-23957.
• Franco A, Kompella SN, Akondi K, Melaun C, Daly N, Luetje CW, Alewood PF, Craik DJ, Adams DJ and Mari F. (2012). RegIIA: An α4/7-conotoxin from the venom of Conus regius that potently blocks α3β4 nAChRs. Biochemical Pharmacology83, 419-426.
• Knapp O, Nevin ST, Yasuda T, Lawrence N, Lewis RJ and Adams DJ. (2012). Biophysical properties of Na_v1.8/Na_v1.2 chimeras and inhibition by μO-conotoxin MrVIB. British Journal of Pharmacology166, 2148-2160.
• Bongiorno D, Schuetz F, Poronnik and Adams DJ (2011). Regulation of voltage-gated ion channels in excitable cells by ubiquitin ligases Nedd4 and Nedd4-2. Channels (Austin) 5 (1) 79-88.
• Daly NL, Callaghan B, Clark RJ, Nevin ST, Adams DJ and Craik DJ (2011). Structure and Activity of alpha-contoxin PeIA at nicotinic acetylcholine receptor subtypes and GABAB receptor-coupled N-type calcium channels. J Biol Chem286 (12) 10233-37.
• Dantas de Araujo, Callaghan B, Nevin ST, Daly NL, Craik DJ, Moretta M, Hopping G, Christie MJ, Adams DJ and Alewood PF (2011). Total synthesis of analgesic conotoxin MrVIB via selenocysteine-assisted folding. Angewandte Chemie – International Edition50, 6527-6529.
• Halai R, Callaghan B, Daly NL, Clark RJ, Adams DJ and Craik DJ (2011). Effects of cyclization on stability, structure and activity of α-conotoxin RgIA at the α9α10 nicotinic acetylcholine receptor and GABA_B receptor. Journal of Medicinal Chemistry54, 6984-6992.
• Klimis H, Adams DJ, Callaghan B, Nevin S.T, Alewood PF, Vaughan CW, Mozar CA and Christie MJ (2011). A novel mechanism of inhibition of high-voltage activated calcium channels by α-conotoxins contributes to relief of nerve injury-induced neuropathic pain Pain152 (2) 259-266.
• Callaghan B and Adams DJ (2010). Analgesic alpha-conotoxins Vc1.1 and RgIA inhibit N-type calcium channels in sensory neurons of alpha9 nicotinic receptor knockout mice. Channels4. (1) 51-54.
• Clark RJ, Jensen J, Nevin ST, Callaghan BP, Adams DJ. (2010). The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic Pain Angew. Chem. Int. Ed. 49 6545-6548.
• Grishin AA, Wang CI, Muttenthaler M, Alewood PF, Lewis RJ and Adams DJ (2010). Alpha-conotoxin AuIB isomers exhibit distinct inhibitory mechanisms and differential sensitivity to stoichiometry of alpha3beta4 nicotinic acetylcholine receptors. J Biol Chem. 285 (29) 22254-63.
• Yasuda T and Adams DJ (2010). Physiological roles of ion channels in adult neural stem cells and their progeny. J. Neurochem.114, (4) 946-59.

Key laboratory of Animal Models and Human Disease Mechanisms

2015-06-10