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Molecules isolated from venomous marine cone snails can be used to discover new drug leads for pain management and the treatment of chronic pain, depression and drug addiction. By introducing subtle modifications to key conotoxins that target a particular receptor, we can further refine their biological properties to develop more effective drugs with fewer side effects than present options.
Dr. Armishaw’s lab is interested in developing novel research tools and drugs for studying pain management, depression and drug addiction using molecules isolated from venomous marine cone snails. Cone snails use an elaborate biological harpoon mechanism to deliver deadly venom that swiftly immobilizes their fast moving prey. Their venom, which is composed of a complex mixture of disulfide rich peptides known as conotoxins, acts on an array on ion-channels and receptors in the central and peripheral nervous systems. There is enormous scope for using conotoxins to develop new bioactive ligands as probes for studying nervous system functions, with potential for developing new drugs for treating a host of neurological conditions. By introducing subtle modifications to key conotoxins through use of synthetic combinatorial chemistry, we can further refine their biological properties to develop more effective drugs with fewer side effects than present options.
Figure 1: Conus striatus with its proboscis extended ready to strike at its prey
Dr. Armishaw completed his Bachelor of Science (Honours) degree in 1998 from the University of Melbourne, Australia, followed by his Ph.D. in Chemistry at the Institute for Molecular Bioscience, University of Queensland, Australia, ("Controlling Cysteine Frameworks in Structurally Constrained Conotoxins") in 2003. After completing his Ph.D., he continued working at the University of Queensland as a post doctoral Research Officer before undertaking post doctoral research at the Faculty of Pharmaceutical Sciences at the University of Copenhagen, Denmark with Professor Kristian Strømgaard where he performed structure-activity relationship studies of α-conotoxins targeting neuronal nicotinic acetylcholine receptors. Dr. Armishaw joined the Torrey Pines Institute in February 2008 as an Assistant Member where he is currently using conotoxins to develop novel research tools and drug leads for treating pain and drug addiction.
- July 1999-July 2003: Doctor of Philosophy (Biological Chemistry), Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
- Jan 1999 – Dec 1998: Bachelor of Science (Honours 1st Class)(Major – Chemistry), Department of Chemistry, The University of Melbourne, Australia
- Feb 2008 - Present: Assistant Member Torrey Pines Institute for Molecular Studies, Port St Lucie, Florida
- Jan 2006 - Dec 2007: DRA post-doctoral research fellow Department of Medicinal Chemistry Faculty of Pharmaceutical Sciences The University of Copenhagen, Denmark
- July 2003 - Dec 2005: NHMRC research officer Institute for Molecular Bioscience The University of Queensland, Brisbane, Australia
- Jan 1999 - July 1999: Research Assistant Department of Chemistry The University of Melbourne, Australia
- American Peptide Society
- American Chemical Society
- Society for Neuroscience
- July 2010-June 2013 – Principal investigator, State of Florida Department of Health, James & Esther King research foundation new investigator award, “α-Conotoxins as subtype-specific nicotinic acetylcholine receptor antagonists for studying tobacco addiction
- July 2010-June 2011 – Principal investigator, Arthritis and Chronic Pain Research Institute, Development selective norepinephrine reuptake inhibitors using conotoxin frameworks
- July 2009-June 2010 – Principal investigator, Arthritis and Chronic Pain Research Institute, Synthetic combinatorial libraries of α-conotoxins targeting neuronal nicotinic acetylcholine receptors
Scholarships & Fellowships
- Drug Research Academy Post Doctoral Fellowship, University of Copenhagen, 2006-2007.
- University of Queensland Graduate School Research Scholarship, 1999-2003.
- University of Queensland Graduate School Research Travel Award, 2001.
- Royal Australian Chemical Institute, best Ph.D. thesis award in biomolecular chemistry, 2003.
- Deans commendation list, outstanding higher degree thesis, University of Queensland, 2003.
Selected Publications (10 of 19)
- Armishaw, C. J.; Jensen, A. A.; Balle, L. D.; Scott, K. C. M.; Sørensen, L.; Strømgaard, K. Improving the stability of α-conotoxin AuIB through N-to-C cyclization: The effect of spacer length on stability and activity at nicotinic acetylcholine receptors. Antioxidants & Redox Signaling 2011, 14, 65-76.
- Armishaw, C. J.; Singh, N.; Medina-Franco, J.; Clark, R. J.; Scott, K. C. M.; Houghten, R. A.; Jensen, A. A. A synthetic combinatorial strategy for developing α-conotoxin analogs as potent α7 nicotinic acetylcholine receptor antagonists. J. Biol. Chem. 2010, 285, 1809-1821.
- Armishaw, C. J. Synthetic α-conotoxin mutants as probes for studying nicotinic acetylcholine receptors and in the development of novel drug leads. Toxins 2010, 2, 1470-1498.
- Armishaw, C. J.; Dutton, J. L.; Craik, D. J.; Alewood, P. F. Establishing regiocontrol of disulfide bond isomers of α-conotoxin ImI via the synthesis of N-to-C cyclic analogs. Biopolymers 2010, 94, 307-313.
- Mejia, M.; Heghinian, M. D.; Busch, A.; Armishaw, C. J.; Marí, F.; Godenschwege, T. A. A novel approach for in vivo screening of toxins using the Drosophila giant fiber circuit. Toxicon 2010, 56, 1398-1407.
- Muttenthaler, M.; Nevin, S. T.; Grishin, A. A.; Ngo, S. T.; Choy, P. T.; Daly, N. L.; Hu, S.-H.; Armishaw, C. J.; Wang, C.-I.; Lewis, R. J.; Martin, J. L.; Noakes, P. G.; Craik, D. J.; Adams, D. J.; Alewood, P. F. Solving the α-conotoxin folding problem: Efficient selenium-directed on-resin generation of more potent and stable nicotinic acetylcholine receptor antagonists. J. Am. Chem. Soc. 2010, 132, 3514-3522.
- Armishaw, C.; Jensen, A. A.; Balle, T.; Clark, R. J.; Harpsøe, K.; Skonberg, C.; Liljefors, T.; Strømgaard, K. The rational design of α-conotoxin analogues targeting α7 nicotinic acetylcholine receptors: Improved antagonistic activity by incorporation of proline derivatives. J. Biol. Chem. 2009, 284, 9498-9512.
- Armishaw, C. J.; Daly, N. L.; Nevin, S. T.; Adams, D. J.; Craik, D. J.; Alewood, P. F. a-Selenoconotoxins: A new class of potent α7 neuronal nicotinic receptor antagonists. J. Biol. Chem. 2006, 281, 14136-14143.
- Lovelace, E. S.; Armishaw, C. J.; Colgrave, M. L.; Wahlstrom, M. E.; Alewood, P. F.; Daly, N. L.; Craik, D. J. Cyclic MrIA: A stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter. J. Med. Chem. 2006, 49, 6561-6568.
- Armishaw, C. J.; Alewood, P. F. Conotoxins as research tools and drug leads. Curr. Protein Pept. Science 2005, 6, 221-240.
- Craik, D.J., Daly, N.L., Nielsen, K.J., Armishaw, C.J., Clark, R.J., Alewood, P.F.; Cyclised conotoxin peptides U.S. Pat. Appl. Publ. 2005 44pp., Continuation in part of U.S. Ser. No. 787,082.