Bachelor Medical Science (1st class Honors) University of Technology, Sydney, 2002
Graduate Diploma in Drug Discovery and Pharmaceutical Science. Unievrsity of Melbourne, 2005
PhD (Medical Science), University of Technology, Sydney, 2009
Central Visual Pathways
Recombinant Expression Systems
Cell Biology and Genetics
Medical and Applied Physiology
Gunning, SJ, Chung, KK, Donaldson, PJ & Webb, KF 2012, 'Identification of a nonselective cation channel in isolated lens fiber cells that is activated by cell shrinkage', American Journal of Physiology - Cell Physiology, vol. 303, no. 12, pp. 1252-1259.View/Download from: UTS OPUS or Publisher's site
The initiation of lens cataract has long been associated with the development of a membrane leak in lens fiber cells that depolarizes the lens intracellular potential and elevates intracellular Na+ and Ca2+ concentrations. It has been proposed that the leak observed in cataractous lenses is due to the activation of a nonselective cation (NSC) conductance in the normal electrically tight fiber cells. Studies of the membrane properties of isolated fiber cells using the patch-clamp technique have demonstrated a differentiation-dependent shift in membrane permeability from K+-dominated in epithelial and short fiber cells toward larger contributions from anion and NSC conductances as fiber cells elongate. In this study, the NSC conductances in elongating lens fiber cells are demonstrated to be due to at least two distinct classes: a Gd3+-sensitive, mechanosensitive channel whose blockade is essential for obtaining viable isolated fiber cells, and a second Gd3+-insensitive, La3+-sensitive conductance that appears to be activated by cell shrinkage. This second conductance was eliminated by the replacement of extracellular Na+ with the impermeant cation N-methyl-D-glucamine and was potentiated by both hypertonic stress and isosmotic cell shrinkage evoked by the replacement of extracellular Cl- with the impermeant anion gluconate.
Gunning, SJ, Maggio, FJ, Windley, MJ, Valenzuela, S, King, GF & Nicholson, GM 2008, 'The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels', FEBS Journal, vol. 275, no. 16, pp. 4045-4059.View/Download from: UTS OPUS or Publisher's site
The Janus-faced atracotoxins are a unique family of excitatory peptide toxins that contain a rare vicinal disulfide bridge. Although lethal to a wide range of invertebrates, their molecular target has remained enigmatic for almost a decade. We demonstrate here that these toxins are selective, high-affinity blockers of invertebrate calcium activated K+ (KCa) channels. J-ACTX-Hv1c, the prototypic member of this toxin family, selectively blocked KCa channels in cockroach unpaired dorsal median neurons with an IC50 of 2 nM, but it did not significantly affect a wide range of other voltage activated potassium (KV), calcium (CaV), or sodium (NaV) channel subtypes. J ACTX-Hv1c blocked heterologously expressed cockroach BKCa (pSlo) channels without a significant shift in the voltage-dependence of activation. However, the block was voltage-dependent, indicating that the toxin likely acts as a pore blocker rather than a gating modifier. The molecular basis of the insect selectivity of J-ACTX-Hv1c was established by its failure to significantly inhibit mouse mSlo currents (IC50 ~10 Î¼M) and its lack of activity on rat dorsal root ganglion neuron IK(Ca). This study establishes the Janus-faced atracotoxins as valuable tools for the study of invertebrate KCa channels and suggests that KCa channels might be a potential insecticide target.
Birinyi-Strachan, LC, Gunning, SJ, Lewis, RJ & Nicholson, GM 2005, 'Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons', Toxicology And Applied Pharmacology, vol. 204, no. 2, pp. 175-186.View/Download from: UTS OPUS or Publisher's site
The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath applic
Gunning, SJ, Chong, Y, Khalife, A, Hains, PG, Broady, KW & Nicholson, GM 2003, 'Isolation of delta-missulenatoxin-Mb1a, the major vertebrate-active spider delta-toxin from the venom of Missulena bradleyi (Actinopodidae)', Febs Letters, vol. 554, no. 1-2, pp. 211-218.View/Download from: UTS OPUS or Publisher's site
The present study describes the isolation and pharmacological characterisation of the neurotoxin ?-missulenatoxin-Mb1a (?-MSTX-Mb1a) from the venom of the male Australian eastern mouse spider, Missulena bradleyi. This toxin was isolated using reverse-phase high-performance liquid chromatography and was subsequently shown to cause an increase in resting tension, muscle fasciculation and a decrease in indirect twitch tension in a chick biventer cervicis nerve-muscle bioassay. Interestingly, these effects were neutralised by antivenom raised against the venom of the Sydney funnel-web spider Atrax robustus. Subsequent whole-cell patch-clamp electrophysiology on rat dorsal root ganglion neurones revealed that ?-MSTX-Mb1a caused a reduction in peak tetrodotoxin (TTX)-sensitive sodium current, a slowing of sodium current inactivation and a hyperpolarising shift in the voltage at half-maximal activation. In addition, ?-MSTX-Mb1a failed to affect TTX-resistant sodium currents. Subsequent Edman degradation revealed a 42-residue peptide with unusual N- and C-terminal cysteines and a cysteine triplet (Cys14-16). This toxin was highly homologous to a family of ?-atracotoxins (?-ACTX) from Australian funnel-web spiders including conservation of all eight cysteine residues. In addition to actions on sodium channel gating and kinetics to ?-ACTX, ?-MSTX-Mb1a caused significant insect toxicity at doses up to 2000 pmol/g. ?-MSTX-Mb1a therefore provides evidence of a highly conserved spider ?-toxin from a phylogenetically distinct spider family that has not undergone significant modification.
Gunning, SJ, Maggio, FJ, Windley, MJ, Valenzuela, S, King, GF & Nicholson, GM 2009, 'Janus-faced atracotoxins are specific blockers of invertebrate KCa channels', 34th Congress of the Federation of European Biochemical Societies, Prague, Czech Republic.
Nicholson, GM, Gunning, SJ, Windley, MJ, Maggio, FJ, Valenzuela, S & King, GF 2009, 'Defining the lethal ion channel targets of insecticidal spider toxins', 16th World Congress on Animal, Plant and Microbial Toxins.
Sollod, B, Gunning, SJ, Wen, S, Gentz, MC, Nicholson, GM & King, GK 2009, 'A dual-target, self-synergizing ion channel toxin from spider venom', 16th World Congress on Animal, Plant and Microbial Toxins, Canberra, ACT.
Nicholson, GM, Gunning, SJ, Maggio, FJ, Windley, MJ, Valenzuela, S & King, GF 2009, 'Identifying novel insecticide targets using insect-specific spider toxins', 3rd International Congress on Natural Peptides to Drugs, Zermatt, Switzerland.
Gunning, SJ, Maggio, FJ, Valenzuela, S, Broady, KW, King, GK & Nicholson, GM 2006, 'Pharmacophore mapping of the Îº-atracotoxins: selective insect potassium channel blockers that reveal a novel insecticide target', 15th World Congress on Animal, Plant and Microbial Toxins, Glasgow, Scotland.
Gunning, SJ, Maggio, FJ, Valenzuela, S, Broady, KW, King, GK & Nicholson, GM 2005, 'Îº-Atracotoxins: Insect potassium channels blockers that reveal a novel insecticide target', Venoms to Drugs 3, Heron Island, QLD.
Sollod, B, Gunning, SJ, Wen, S, Nicholson, GM & King, GK 2005, 'Evolution of a dual target, self-synergizing toxin: implications for insecticide and pharmaceutical discovery', Venoms to Drugs 3, Heron Island, QLD.
Gunning, SJ, Maggio, FJ, Valenzuela, S, Broady, KW, King, GK & Nicholson, GM 2005, 'Selective actions of Îº-atracotoxins on insect KCa channels: electrophysiological validation of the insect target and pharmacophore', 7th Asia Pacific Congress on Animal, Plant and Microbial Toxins, Cebu City, Philippines.
Gunning, SJ, Maggio, FJ, King, GK & Nicholson, GM 2004, 'Îº-Atracotoxins: Insect potassium channels blockers that reveal a novel insecticide target.', 8th Symposium of the Pan-American Section of the International Society of Toxinology, Angra dos Reis, Brazil.
Gunning, SJ, Chong, Y, Khalife, A, Hains, PG, Broady, KW & Nicholson, GM 2003, 'Discovery of a novel sodium channel neurotoxin delta-missulenatoxin Mb1a from the venom of the Eastern mouse spider Missulena bradleyi', 14th World Congress on Animal, Plant and Microbial Toxins, Adelaide.
University of Auckland (Molecular Vision Laboratory)
University of Technology, Sydney (Neurotoxin Research Group)