Associate Professor Graham M Nicholson

Phone: +61 2 9514 2230

Fax: +61 2 9514 8206

Graham.Nicholson@uts.edu.au

Academic Qualifications

BSc(Hons), PhD (Sydney), GradCertHigherEd (UTS), MIST

Research Interests and activities

The potency and specificity of many animal, plant or microbial toxins make them attractive drug leads and a number of toxins have proved to be invaluable tools in the study of the structure and function of the nervous system and how nerve cells communicate.

For example, toxins have been extremely useful for probing the diversity of ion channels, defining various classes of these channels and for identifying ion channel subtypes.

Another potential use of neurotoxins is their application as novel biopesticides for the control of insecticide resistant pests. We are particularly interested in this area of toxinology since Australia contains a large number of highly toxic animals.

This provides us with an, as yet, untapped source of highly specific toxins to use as molecular probes, and lead compounds for therapeutic and insecticidal agents.

Dr Nicholson is the leader of the Neurotoxin Research Group. He is interested in isolation as well as structural and pharmacological characterisation of animal neurotoxins.

Dr. Nicholson has been responsible for the isolation and pharmacological characterisation of a wide range of neurotoxins from spider, snake, scorpion and dinoflagellate venoms/toxins particularly those that target the ion channels. Dr. Nicholson's laboratory employs intracellular, patch clamp, ion flux and radioligand binding techniques as well as HPLC separation of venom, organ bath pharmacology and acute toxicity testing techniques. He has published over 50 international refereed publications on toxins and toxicology.

National and international contacts

• Dr. Richard Lewis

  Institute for Molecular Bioscience, University of Queensland, St Lucia QLD 4072, Australia



• Assoc. Prof. Kevin Broady

  Department of Cell & Molecular Biology, University of Technology, Sydney, St. Leonards, NSW 2065, Australia



• Dr. Gerardo Corzo

  Suntory Institute for Bioorganic Research, Osaka, Japan



• Dr. Mike Davies

  Heart Research Institute, Camperdown NSW 2006, Australia



• Dr Dalia Gordon

  Department of Plant Sciences, Tel-Aviv University, Ramat-Aviv, Tel Aviv 69978 Israel



• Dr. Wayne Hodgson

  Monash Venom Group, Department of Pharmacology, Monash University, Clayton VIC 3168 Australia



• Prof. Glenn King

  Department of Biochemistry, University of Connecticut Health Center, Farmington CT 06032, USA



• Dr. Ken Winkel

  Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, VIC 3010, Australia

Research topics for honours and postgraduate students

• Pharmacological characterisation of ion channel modulators from spider and scorpion venom
• Isolation and characterisation of insect-selective arachnid neurotoxins: leads for novel biopesticides
• Cross reactivity of Australian spider antivenoms for the treatment of related and overseas spider envenomation
• Neurotransmitter release and its modulation by presynaptic snake neurotoxins

Research staff and students

PhD Students

• Simon Gunning BMedSc(Hons)
• Youmie Chong BMedSc(Hons)
• Michelle Little MSc
• Suping Wen MMed

Honours Students

positions are currently available for Honours students

Honours projects available

Recent Neurotoxin Research Group Alumni

• Dr Andis Graudins MBBS, PhD, FACEM

  Conjoint Senior Lecturer UNSW Staff Specialist - Emergency Medicine, Consultant Toxicologist

  Prince of Wales Hospital, Randwick, NSW, Australia

  andis@graudins.com




• Dr Liesl-Birinyi-Strachan PhD

  Health Outcomes Analyst, Medical Technology Assessment Group (M-TAG), Chatswood NSW, Australia

  lbstrachan@m-tag.net

Selected Publications (1998-2004)

• Nicholson GM, Graudins A, Wilson HI, Little M, Broady KW (2004) Arachnid toxinology in Australia: clinical toxicology to potential applications [invited review]. Toxicon, in press.


• Strachan LC, Gunning SJ, Lewis RJ, Nicholson GM (2004) Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons. Toxicology and Applied Pharmacology, in press.


• Nicholson GM, Little MJ, Birinyi-Strachan LC (2004) Structure and function of delta-atracotoxins: lethal neurotoxins targeting the voltage-gated sodium channel [invited review]. Toxicon, 43, 587-599.


• Tran Y, Craig A, Bartrop R, Nicholson GM (2004) Time course and regional distribution of cortical changes during acute alcohol ingestion. International Journal of Neuroscience, 114, 863-878.


• Alewood D, Birinyi-Strachan LC, Pallaghy PK, Norton RS, Nicholson GM, Alewood PF (2003) Synthesis and characterization of delta-atracotoxin-Ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus). Biochemistry, 42(44), 12933- 2940


• Nicholson GM, Little MJ, Birinyi-Strachan LC (2003) Structure and function of delta-atracotoxins: lethal neurotoxins targeting the voltage-gated sodium channel [invited review]. Toxicon, in press.


• Alewood D, Birinyi-Strachan LC, Pallaghy PK, Norton RS, Nicholson GM, Alewood PF (2003) Synthesis and characterization of delta-atracotoxin-Ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus). Biochemistry.


• Gunning SJ, Chong Y, Khalife AA, Hains PG, Broady KW, Nicholson GM (2003) Isolation of delta-missulenatoxin-Mb1a, the major vertebrate-active spider-toxin from the venom of Missulena bradleyi (Actinopodidae). FEBS Letters, 554, 211-218.


• Nicholson GM, Graudins A (2003) Antivenoms for the treatment of spider envenomation [invited review]. Journal of Toxicology and Toxin Reviews, 22, 35-59.


• Nicholson GM, Blanche T, Mansfield K, Tran Y (2002) Differential blockade of neuronal voltage-gated sodium and potassium channels by antidepressant drugs. European Journal of Pharmacology, 452, 35-48.


• Nicholson GM, Graudins A (2002) Spiders of medical importance in the Asia-Pacific: atracotoxin, latrotoxin and related spider neurotoxins [invited review]. Clinical and Experimental Pharmacology and Physiology, 29, 785-794.


• Gordon D, Gilles N, Bertrand D, Molgo J, Nicholson GM, Sauviat MP, Benoit E, Shichor I, Lotan I, Gurevitz M, Kallen RG, Heinemann SH (2002) Scorpion toxins differentiate among neuronal sodium channel subtypes: Nature's guide for design of selective drugs. In: Perspectives in Molecular Toxinology (Ed. A. Menez), pp. 215-238, John Wiley & Sons, ISBN: 0-471-49503-4.


• Gilles N, Harrison G, Karbat I, Gurevitz M, Nicholson GM and Gordon D (2002) Variations in receptor site-3 on rat brain and insect sodium channels highlighted by binding of a funnel-web spider delta-atracotoxin. European Journal of Biochemistry, 269, 1500-1510. (2.999)


• Graudins A, Gunja N, Broady KW, Nicholson GM (2002) Clinical and in vitro evidence for the efficacy of Australian red-back spider (Latrodectus hasselti) antivenom in the treatment of Brown cupboard spider (Steatoda grossa) envenomation. Toxicon, 40, 767-775. (2.003)


• Graudins A, Wilson D, Alewood PF, Broady KW, Nicholson GM (2002) Cross-reactivity of Sydney funnel-web spider antivenom: Neutralization of the in vitrotoxicity of other Australian funnel-web (Atrax and Hadronyche) spider venoms. Toxicon, 40, 259-266.


• Wang X-H, Connor M, Wilson D, Wilson HI, Nicholson GM, Smith R, Shaw D, Mackay JP, Alewood PF, Christie MJ, King GF (2001) Discovery and structure of a potent and highly specific blocker of insect calcium channels. Journal of Biological Chemistry, 276, 40306-40312.


• Grolleau F, Stankiewicz M, Birinyi-Strachan LC, Wang X-H, Nicholson GM, Pelhate M, Lapied B (2001) Electrophysiological analysis of the neurotoxic action of a funnel-web spider toxin, delta-atracotoxin-Hv1a on insect voltage-gated sodium channels. Journal of Experimental Biology, 204, 711-721.


• Graudins A, Padula M, Broady KW, Nicholson GM (2001) Red-back spider (Latrodectus hasselti) antivenom prevents the toxicity of widow spider venoms. Annals of Emergency Medicine, 37, 154-160.


• Rash LD, Birinyi-Strachan LC, Nicholson GM, Hodgson WC (2000) Neurotoxic activity of venom from the Australian eastern mouse spider (Missulena bradleyi). British Journal of Pharmacology, 130 1817-1824


• Gilles N, Chen H, Wilson HI, Le Gall F, Montoya G, Molg? J, Sch?nherr R, Nicholson GM, Heinemann SH, Gordon D (2000) Scorpion alpha- and alpha-like toxins differentially interact with sodium channels in mammalian CNS and periphery. European Journal of Neuroscience, 12, 2823-2832


• Torres AM, de Plater GM, Doverskog M, Birinyi-Strachan LC, Nicholson GM, Gallagher CH, Kuchel PW (2000) Defensin-like peptide-2 from platypus venom: member of a class of peptides with a distinct structural fold. Biochemical Journal, 348, 649-656.


• Wang X-H, Connor M, Smith R, Maciejewski MW, Howden MEH, Nicholson GM, Christie MJ, King GF (2000) Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge. Nature Structural Biology, 7, 505-513 (10.446)


• Szeto TH, Birinyi-Strachan LC, Wang X-H, Smith R, Connor M, Christie MJ, King GF, Nicholson GM (2000) Isolation and pharmacological characterisation of delta-atracotoxin-Hv1b, a vertebrate-selective sodium channel toxin. FEBS Letters, 470, 293-299


• Szeto TH, Wang XH, Smith R, Connor M, Christie MJ, Nicholson GM and King GF (2000) Isolation of a funnel-web spider polypeptide with homology to mamba intestinal toxin 1 and the embryonic head inducer Dickkopf-1. Toxicon, 38, 429-442.


• Graudins A, Padula M, Broady KW, Nicholson GM (2000) Evidence for red-back spider antivenom efficacy in the prevention of envenomation by other widow-spiders (genus Latrodectus). Journal of Toxicology & Clinical Toxicology, 38, 205-206.


• Torres AM, Wang X, Fletcher JI, Alewood D, Alewood PF, Smith R, Simpson R, Nicholson GM, Sutherland SK, Gallagher CH, King GF and Kuchel PW (1999) Solution structure of a defensin-like peptide from platypus venom. BiochemicalJournal, 341, 785-794.


• Strachan LC, Lewis RJ and Nicholson GM (1999) Differential actions of Pacific ciguatoxin-1 on voltage-gated sodium channel subtypes in mammalian sensory neurons. Journal of Pharmacology and Experimental Therapeutics, 288, 379-388.


• Fletcher JI, Wang X, Connor M, Christie MJ, King GF and Nicholson GM (1999) Spider toxins: a new group of potassium channel modulators. Perspectives in Drug Discovery and Design 15/16, 61-69.

Teaching

Dr Nicholson's skills are in the areas of pharmacology and toxicology. He is the immediate past Course Director for the BMedSc program at UTS. He also teaches on a number of subjects within the academic programs of the Faculty of Science and Faculty of Nursing, Midwifery & Health.

Research Activities

• Chairman, Scientific Program Committee, 6th Asia-Pacific IST Congress on Animal, Plant & Microbial Toxins, Cairns, Australia
• Member, Scientific Program Committee, 14th World IST Congress on Animal, Plant & Microbial Toxins, Adelaide, Australia
• Member, Editorial Council, International Journal Toxicon