Symposium on “toxins and ion channels” Thursday 27 July “Mechanisms and specificity in the interaction of scorpion toxins with voltage-gated sodium channels”
Michael Gurevitz was born in 1946 in Germany and received his BS, MSc and PhD
degrees at the Hebrew University of Jerusalem. He spent six years (1981-1986) in the
United States before he joined Tel Aviv University, where he serves now as a Professor at
The Department of Plant Sciences. His interests divide between Toxinology and plant
molecular biology. In the early 90s he has established a successful expression system for
scorpion toxins affecting voltage-gated sodium channels, which has been used
extensively to study structure-activity relationship and the mechanism by which these
toxins interact with their target channels.
The Gurevitz laboratory focuses in their toxinology research on molecular mechanisms
underlying the mode of action and specific recognition of insect and mammalian Na+
channels by a variety of pharmacologically distinct scorpion toxins. This study is motivated
by the need to develop new approaches to the design of environmentally-safe,
biodegradable insecticides and selective drugs in medicine. The experimental approach
combines methods of various disciplines (molecular genetics, neuropharmacology,
electrophysiology, structural biology) and involves extensive collaboration with several
research groups in Israel and abroad. Selected publications (from the last 2 years)
Cohen L, Karbat I, Gilles N, Froy O, Corzo G, Angelovici R, Gordon D & Gurevitz M (2004) Dissection of the functional surface of an anti-insect excitatory toxin illuminates a putative ‘hot spot’ common to all scorpion α-toxins affecting Na+ channels. J Biol Chem 279:8206-8211. Karbat I, Cohen L, Gilles N, Gordon D & Gurevitz M (2004) Conversion of a scorpion toxin agonist into an antagonist highlights an acidic residue involved in voltage sensor trapping during activation of neuronal Na+ channels. FASEB J 18:683-689. Karbat I, Frolow F, Froy O, Gilles N, Cohen L, Turkov M, Gordon D & Gurevitz M (2004) Molecular basis of the high insecticidal potency of scorpion α-toxins. J Biol Chem 279:31679-31686. Tan J, Liu Z, Wang R, Huang Z, Chen AC, Gurevitz M & Dong K (2005) Identification of amino acid residues critical for pyrethroid binding to insect sodium channels. Mol Pharmacol 67:513-522. Corzo G, Escoubas E, Villegas E, Karbat I, Gordon D, Gurevitz M, Nakajima T & Gilles N (2005) A spider toxin that induces a typical effect of scorpion α-toxins but competes with β-toxins on binding to insect sodium channels. Biochemistry 44:1542-1549. Cohen L, Karbat I, Gilles N, Ilan N, Gordon D & Gurevitz M (2005) Common features in the functional surface of scorpion β-toxins and elements that confer specificity for insect and mammalian voltage-gated Na-channels. J Biol Chem 280:5045-5053. Strugatsky D, Zilberberg N, Ilan N, Turkov M, Cohen L, Stankiewicz M, Pelhate M, Gilles N, Gordon D & Gurevitz M (2005) Expression of a gene family encoding a novel scorpion depressant toxin illuminates the key role of asparagine-58 in activity on insect neuronal sodium channels. Biochemistry 44:9179-9187.
Symposium on “toxins and ion channels” Thursday 27 July “Glycerotoxin, a new tool to dissect synaptic vesicle recycling”
Dr Meunier’s research focuses on understanding, at the molecular level, the dynamics events mediating neuronal/hormonal secretions and synaptic plasticity (how neurons survive, connect and communicate). To study these fundamental physiological processes, two main strategies are used: first, taking advantage of the exquisite selectivity of neurotoxins to selectively dissect these mechanisms, and second, examining the role played by members of certain classes of lipid in modulating various steps of neuronal secretions. The hope is to establish novel avenues in our understanding of neuronal communications that will lead to novel therapeutic strategies to tackle neuronal diseases. Selected Publications:
Rickman, C., Meunier, F. A., Binz, T. and Davletov, B. A. (2004). High affinity interaction of syntaxin and SNAP-25 on the plasma membrane is abolished by botulinum toxin E. J. Biol. Chem. 279:644-51. Foran, P.G., Davletov, B., and Meunier F. A. (2003). Getting muscles moving again after botulinum toxin : novel therapeutic challenges. Trends in Molecular Medicine 9: 9291-9299. Meunier, F.A., Feng, Z.P., Molgo, J., Zamponi, G. and Schiavo G. (2002). Glycerotoxin from Glycera convoluta stimulates neurosecretion by targeting N-type Ca2+ channels Cav2.2. EMBO J. 21: 6733-6743. Osborne, S.L., Meunier, F. A. and Schiavo G. (2001). Phosphoinositides as Key Regulators of Synaptic Function. Neuron 32: 9-12. Symposium on “toxins and ion channels” Thursday 27 July “Potassium channel toxins - a trail from cortex to channel subtype”
BSc (Hons) Aberdeen University, 1982; PhD, John Curtin School of Medical Research, Australian National University 1986; Postdoctoral Fellow, Sandoz Institute 1986-1988; Principal Scientist, Wyeth Research UK 1988- 1994; Governors’ Lecturer, Biochemistry, Imperial College London 1995- 2002; Professor of Neuroscience, University of Strathclyde 2002-2004; Eberhard Buhl Chair of Neurobiology, University of Leeds (2004 - ); Wellcome Trust Neurosciences and Mental Health Committee; Scientific Advisory Board, Biofocus PLC; MRC Brain Sciences Panel; Reviewing and Topical Reviews Senior Editor, Journal of Physiology. Research programme: Understanding the role of neuronal ion channels The challenge of understanding brain and neuronal function in health and disease requires an interdisciplinary attack at multiple levels, from genomic information through molecular, cellular and systems approaches. My background is in physiology with my present research focussing mainly on the characterization of voltage-gated potassium channels. Potassium channels are crucial regulators of the excitability of nerve cells, and they have consequently become an important target for academic and drug research. Indeed, I first worked on these in the pharmaceutical industry. My interests and experience ranges from obscure biophysical measurements of channel function up to complex neuronal networks in brain slices and isolated, intact, cerebellum. Throughout my career, I’ve come back again and again to using toxins as selective tools to dissect out roles of specific ion channels. Our lab employs a wide range of techniques and has developed some novel preparations. At the most basic level, we employ site directed mutagenesis techniques to unravel which parts of cloned potassium channel subunits contribute to their opening and their distinctive pharmacology. Furthermore, we examine ‘native’ voltage gated potassium currents in nerve cells, trying to understand the molecular identity of these using antibody labelling and physiological and pharmacological ‘fingerprinting’ and transgenic animals.
Another major interest in our lab is the study of changes in sensory neurons following nerve injury. Neuropathic pain is a huge health problem, and unfortunately, despite intensive study, we still know very little about the fundamental mechanisms involved. Using animal and organotypic culture models, we are investigating excitability changes often associated with anatomical remodelling, including sprouting of axonal terminals around primary afferent somata in dorsal root ganglia. Selected recent publications: AP SOUTHAN & B ROBERTSON (2000) Electrophysiological characterization of voltage-gated K+ currents in cerebellar basket and Purkinje cells: Kv1 and Kv3 channel subfamilies are present in basket cell nerve terminals. Journal of Neuroscience 20, 114-122. JM MILLAR, L BARRATT, AP SOUTHAN, KM PAGE, REW FYFFE, B ROBERTSON, & A MATHIE (2000) A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proceedings of the National Academy of Sciences (USA) 97, 3614-3618. T BUSHELL, C CLARKE, A MATHIE & B ROBERTSON (2002) Pharmacological characterisation of a non-inactivating outward current in mouse cerebellar Purkinje neurones. British Journal of Pharmacology 135, 705-712. NP MORRIS, REW FYFFE & B ROBERTSON (2004) Characterisation of the hyperpolarization-activated current (Ih) in the medial septum/diagonal band complex in the mouse. Brain Research, 1006, 74-86. SYM YEUNG, D THOMPSON, Z WANG, D FEDIDA, B ROBERTSON (2005) Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: Significance for CNS and biophysical studies. Journal of Neuroscience, 25, 8735-8745
John W. Daly Plenary lecture Thursday 27 July John W. Daly “Alkaloids as probes for ionic channels”
Dr. Daly was born and raised in Portland, Oregon. He received in 1954 a bachelors degree in Biochemistry and in 1955 a masters degree in Organic Chemistry at Oregon State College and then a Ph.D. in Organic Chemistry at Stanford University in 1958. After a two year postdoctorate in the Laboratory of Chemistry at NIH, he became a permanent member of the staff in 1960, a section chief in 1969 and the founding chief of the Laboratory of Bioorganic Chemistry in 1981. He became a NIH Scientist Emeritus in January 2003. During his five decades at NIH, his research has spanned many disciplines, being involved in isolation, structure elucidation and synthesis of novel natural products and receptor agonists/ antagonists and in the elucidation of their mechanism of action with a focus on receptors, ion channels, and second messenger formation in the nervous system. High points in his career include the discovery of the NIH Shift, the introduction of a prelabeling technique for investigation of cyclic AMP generation in intact cells, the introduction of a variety of selective agonists and antagonists as probes and radioligands for adenosine receptors, the delineation of biological targets for caffeine and other xanthines in the central nervous system, the discovery of the direct activation of adenylyl cyclase by forskolin, the discovery of the activation of phosphoinositide breakdown by maitotoxin, and the discovery that loperamide is a unique modulator of a capacitative calcium influx pathway and that N-substituted dihydropyridines are selective blockers of such channels. Over four decades, he has been involved both in field collection and as a chemist and pharmacologist in the discovery and structure elucidation of a wide range of over 800 alkaloids of twenty some structural classes in amphibian skin and elucidation of the basis for their biological activity. Such compounds include batrachotoxins, histrionicotoxins, pumiliotoxins, and epibatidine. Certain of these alkaloids are now widely used as research tools; batrachotoxin as a selective activator of sodium channels, histrionicotoxins as blockers of nicotinic channels, pumiliotoxins as sodium channel agents with biomedical potential as cardiotonic agents and epibatidine as nicotinic agonist with potent analgetic activity. Analogues of epibatidine are the subject of clinical trials for a treatment of chronic pain of neuropathies, cancer and arthritis. Many of the alkaloids discovered by Dr. Daly have been the target of synthetic research in laboratories world-wide. Dr. Daly’s research presently focuses on the structure and biological activity of further novel alkaloids found in amphibian skin and on the dietary origin of such alkaloids. Dr. Daly has been the recipient of other awards in recognition of his achievements. He was elected to the National Academy of Sciences, USA in 1997. Besides his abiding interest in field work and research, Dr. Daly is an avid fisherman. Selected publications from a bibliography of over 600 articles and reviews follow. 1. Seamon, K.B., and Daly, J.W.: Forskolin: A unique diterpene activator of cyclic AMP- generating systems. J. Cyclic Nucleotide Res. 7: 201-224, 1982. 2. Badio, B., and Daly, J.W. Epibatidine, a potent analgetic and nicotinic agonist. Mol Pharmacol. 45: 563-569, 1994. 3. Daly, J.W., Kaneko, T., Wilham, J., Garraffo, H.M., Spande, T.F., A. Espinosa and Donnelly, M.A. Bioactive alkaloids of frog skin: Combinatorial bioprospecting reveals that pumiliotoxins have an arthropod source. Proc. Natl. Acad. Sci. U.S.A. 99: 13996-14001, 2002. 4. Daly, J.W. Ernest Guenther Award in Chemistry of Natural Products. Amphibian skin: A remarkable source of biologically active arthropod alkaloids. J. Med. Chem. 46: 445-452, 2003. 5. Fitch, R.W., Garraffo, H.M., Spande, T.F., Yeh, H.J.C. and Daly, J.W. Bioassay-guided isolation of epiquinamide, a novel quinolizidine alkaloid and nicotinic agonist from an Ecuadoran poison frog, Epipedobates tricolor. J. Nat. Prod. 66: 1345-1350, 2003. 6. Dumbacher, J.P., Wako, A., Derrickson, S.R., Samuelson, A., Spande, T.F., and Daly, J.W. Melyrid beetles (Choresine): A putative source for the batrachotoxin alkaloids found in poison- dart frogs and toxic passerine birds. Proc. Natl. Acad. Sci. U.S.A. 101: 15857-15860, 2004.
7. Daly, J.W., Spande, T.F., and Garraffo, H.M. Alkaloids from amphibian skin: A
tabulation of over eight-hundred compounds. J. Nat. Prod. 68: 1556-1575, 2005.
Michel Lazdunski Plenary lecture Thursday 27 July Michel Lazdunski “Ion channels, toxins, and pain”
Michel Lazdunski is professor at the Medical School of the University of Nice – Sophia Antipolis He holds the chair of Molecular Pharmacology at the Institut Universitaire de France. A world-renowned specialist of ion channels, Michel Lazdunski and his team have made internationally recognized contributions to basic research and to applied research in pharmacology and pathology. These range from understanding the mechanisms underlying oral antidiabetics, and inhalational anesthetics, to the mechanisms of pain perception, cardiac arrhythmia, convulsions, and cerebral ischemia. Over the last 30 years, Michel Lazdunski and his group have introduced and/or analyzed the machanisms of a large variety of toxins, particularly toxins for voltage-sensitive Na+ channels, voltage-sensitive K+ channels, Ca2+-sensitive K+ channels, voltage-sensitive Ca2+ channels and ASIC channels. They have also worked on several other types of venom polypeptides among which toxic phospholipases A2. Michel Lazdunski earned a degree in chemical engineering in 1959, followed by a Ph. D. in physical chemistry in 1962, and a doctorate in biochemistry (doctorat ès sciences) in 1964. He joined the CNRS in 1962. When the CNRS Center for Biochemistry and Molecular Biology opened in 1967 in Marseilles, he took charge of the research group studying the physical chemistry of proteins and enzymology, which he oversaw until 1973. He then created the CNRS Center for Biochemistry in Nice and directed it until 1989, when he founded the CNRS Institute of Molecular and Cell Pharmacology (Institut de pharmacologie moléculaire et cellulaire, IPMC) in Sophia Antipolis, a high tech campus near Nice.
Michel Lazdunski received the CNRS Silver Medal in 1976 for his work on enzymology and the structure of proteins. He has received several prestigious awards, such as the Grand Prix of the French Academy of Sciences for biological research (Charles Léopold Mayer Prize) in 1983, the International Society for Cardiac Research Award in 1984, the Athena Foundation - Institut de France Prize in 1991, the Grand Prix of the French Foundation for Medical Research in 2003. Also in 1991, his team received the Bristol-Myers Foundation Neuroscience Award. Michel Lazdunski is a member of several academies, including the Academia Europaea (1989), the French Academy of Sciences (1991), the Belgian Royal Academy of Medicine (1991). He was awarded the CNRS Gold Medal (2000).
Some recent publications
Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, Salinas M, Lazdunski M. (2004). A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J. 23:1516-25. Chagot B, Escoubas P, Villegas E, Bernard C, Ferrat G, Corzo G, Lazdunski M, Darbon H. (2004). Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid spider Phrixotrichus auratus. Protein Sci. 13:1197-208. Salinas M, Rash LD, Baron A, Lambeau G, Escoubas P, Lazdunski M. (2005).THE RECEPTOR SITE OF THE SPIDER TOXIN PcTx1 ON THE PROTON-GATED CATION CHANNEL ASIC1a. J Physiol. in press.
PESCA SPORTIVA 2014 LICENZA DI PESCA CLASSIFICAZIONE DELLE ACQUE PERIODI DI PESCA E MISURE MINIME (L.R.T. 07/05) (Piano Ittico Provinciale 2012-2015) (D.P.G.R. 54/R/2005 e Piano Ittico Provinciale 2012-2015) Licenze di pesca Elenco delle zone a salmonidi e ciprinidi della provincia di Pistoia, in Per ogni giornata di pesca si applicano i seguenti limiti di
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