international centre for neurotherapeutics

SFI Research Professor of Neurotherapeutics & Director, I.C.N.T.

Professor Dolly is a molecular neurobiologist whose area of expertise encompasses many aspects of communication in the nervous system. After working at Imperial College in London for 27 years where he directed a well-funded Centre for Neurobiochemistry, the award of a prestigious Research Professorship by Science Foundation Ireland attracted him home to Dublin to establish a multi-disciplinary Centre for Neurotherapeutics Research.

His specific research topics include: (i) identification of the proteins and mechanism responsible for quantal release of transmitters, couple with developing novel therapeutics to selectively control this fundamental process, and (ii) the molecular characterisation of neuronal voltage-sensitive K+ channels in normal and diseased states, with the goal of designing inhibitors capable of controlling nerve cell excitability and synaptic transmission.

Professor Dolly is chairperson of the Scientific Advisory Board of the Brain Trust at the Institute of Neurology in London, and has acted as a reviewer for the Medical Research Council, the Biotechnology and Biological Sciences Research Council, Wellcome Trust and the National Science Foundation (USA). He has served on the editorial board of the Journal of Neurochemistry for 10 years, and acts as an editor for Toxicon and the Protein Journal.

Dr Bodeker studied molecular genetics in Trinity College Dublin and subsequently undertook a PhD in biochemistry at the University of Dundee in Scotland. Before joining the I.C.N.T. in July 2004, he spent a number of years as a postdoctoral researcher and resident at the University of California, in the Department of Ophthalmology and later at the Francis I Proctor Foundation. His work at the University of California principally focused on axon guidance and axon repair after injury, and on HSV replication in vivo.

Current work & research interests:

• Gene expression pattern analysis
• Messenger RNA localisation and quantitation within a given cell or tissue
• Differential mRNA stability and its possible effects on cDNA microarray data
• Nuclear and nucleolar architecture
• Inflammation
• Viral epidemiology
• Tissue damage and repair.

Dr Chamotienko is a biochemist who studied at Moscow State University and later at the Shemykin Institute of Bioorganic Chemistry in Pushchino, Russia. He has spent time working in the Shemykin Institute, Max-Planck Institute and prior to moving to the I.C.N.T. in 2004, spent the last 10 years in Imperial College, London in Professor Dolly's Lab.

Current work & research interests:

• Isolation and characterisation of the mammalian, insect- and crustacean specific neurotoxins from the black widow spider venom
• Isolation and characterisation of the K+ channel specific toxins from the mamba snake venom
• Purification and characterisation of the Na+ channel components from crayfish and bovine brain
• Investigation and isolation of the ?a-latrotoxin receptors from mammalian brain
• Investigation of the protein components involved in the neurotransmitter exocytosis
• Studies of the voltage dependant K+ channel, including purification of the channels from mammalian brain, elucidation of the subunit composition of the prevailing native channel complexes, expression of the K+ channel components in mammalian and bacterial cell cultures, toxin - binding, biochemical and biophysical characterisation of the expressed predetermined complexes
• Investigation of the cellular proteins interacting with the K+ channel components
• Studies of the role of phosphorylation in channel functioning.

Dr Gary Lawrence studied at the University of Dundee, and undertook his postgraduate and postdoctoral studies at Imperial College, London. During his time in Imperial College, he pioneered the use of primary cultures of neuroendocrine chromaffin cells for the study of the mechanism of regulated exocytosis of chemical transmitters. He developed methodology for the intoxication of these cells with botulinum and tetanus toxins, endoproteolytic proteins that potently inhibit regulated exocytosis by the specific cleavage of intracellular proteins known as SNAREs, to study in detail the biochemical properties of SNAREs and their functional roles in stimulus-triggered exocytosis. A fluorescence assay was used to quantify exocytosis in conjunction with PAGE and Western blotting techniques to analyse biochemically the SNAREs. For this purpose, he also developed a novel limited proteolysis assay and a two-dimensional PAGE method to exploit unique properties of the SNAREs in order to study them.

Dr Lawrence routinely undertook anaerobic culture of the bacterium Clostridium botulinum and the purification of the botulinum toxins they produce. This involved fermentation, protein precipitation and conventional chromatography techniques (ion-exchange and size-exclusion) and was all performed under Level 3 containment and almost completely within a Class III safety cabinet. As well as being principally responsible for the development of these latter experimental procedures, he was also involved in the design and equipping of the Level 3 laboratory and the development of the protocols and procedures governing its usage. Various other techniques that he has used to assay properties of the botulinum toxins that he or others have produced, include ELISA and reversed phase HPLC assays to measure their proteolytic activities and recordings of nerve-evoked muscle spasms to measure their neuroparalytic potency. In 2001 he was promoted to the position of Laboratory Manager for the containment facility in Imperial College, and moved with Professor Dolly to assume the position of Centre Manager of the I.C.N.T.

Ms Meng is a graduate of Henan University, China and subsequently undertook an M.Sc. in Biochemistry and Molecular Biology in the Life Sciences Institute in Wuhan University, China, followed by studies in hydrobiology genetics at the Chinese Academy of Sciences (CAS). She has since spent time working at both the Institute of Cancer Research and Imperial College in London, before taking up a Research Assistant post in the I.C.N.T. this year.

Current work & research interests:

As a I.C.N.T. Research Assistant, Ms Meng's project is to determine the molecular mechanism of anti-nociceptive function of Botulinum neurotoxins, and study on the Botulinum neurotoxins conjugated single chain antibody targeting on nociceptors on the neuron surface. During the last 12 months, she has successfully dissected and cultured rat trigeminal ganglionic neurons in vitro. Pain related vasoactive neurontransmitter (CGRP and Substance P) release can be monitored from cultured rat trigeminal ganglionic neurons and proofed to be SNARE protein dependent.

Ms NiDhochartaigh graduated from University College Galway in 2003 with a 1st B.Sc. in Biotechnology. During her time as an undergraduate, she also worked as a laboratory technician in Alltech Biotechnologies in the U.S. Ms NiDhochartaigh joined the I.C.N.T. in October 2003 as a PhD student.

Current work & research interests:

• Definition of SNAREs and Potassium Channels for Novel Therapeutics

Dr Raghunath graduated with a 1st class M.B.B.S. from Karnatak University in 1998. He has subsequently worked as a house surgeon (Karnatak University), a research assistant (Swiss Foundation of Neuroscience, Universite de Fribourg, Switzerland and JNCASR, Bangalore, India) and as a visiting scientist (School of Biotechnology, DCU, Ireland). He joined the I.C.N.T. in May 2003 as a Research Assistant.

Current work & research interests:

Novel treatments for Botulism including:

1. creation of viral vectors expressing specific non-cleavable proteins for use in the rescue of exocytosis in affected neurons, and
2. generation of single chain antibodies against surface proteins of motor and sensory neurons for use in the specific targeting of gene therapy vectors.

Dr Sasse is a certified pharmacist who obtained her PhD in medicinal chemistry from the Free University Berlin, Germany. She conducted her post-doctoral studies in molecular biology at INSERM, in Paris, France and worked as a senior staff scientist at the Max-Planck Institute for experimental medicine in Goettingen, Germany before joining the I.C.N.T. in October 2004. Her work was focused on the development of small ligands for G-Protein coupled receptors, and the identification, localization, and pharmacological characterization of new receptor subtypes, as well as the genetic linkage of those receptors to psychiatric disorders.

Dr Wang undertook both his B.Sc. and Ph.D. at Wuhan University China, in the area of molecular virology and molecular biology. He went on to conduct postdoctoral research in molecular virology at the Institute of Life Sciences at Wuhan University, and later at Imperial College, London with Professor Dolly.

Current work & research interests:

• Purification, stabilisation, and characterization of botulinum toxins;
• Development of recombinant botulinum toxins or chimeras as pharmaceuticals;
• Engineering of non-viral transporters for specific targeting to motor neuron and/or sensory neurons.

Dr Zurawski studied for his B.Sc. and M.Sc. in systematic zoology and ecology at Masaryk University, Brno, Czech Republic, and went on to complete his Ph.D. in parasitology between Masaryk and Queen's University, Belfast. He completed a 2-yr postdoctoral research fellowship in intracellular membrane trafficking at the Department of Biochemistry, University College Cork, before joining the I.C.N.T. in June 2004.

Current work & research interests:

The focus of Dr Zurawski's research interests is in understanding the events of intracellular membrane trafficking (exo-endocytosis). He concentrates on imaging and microscopy methods using immunocytochemistry, immunoelectron microscopy, histochemical staining methods altogether with a variety of microscopical techniques (transmission and scanning electron microscopy, fluorescence and confocal scanning laser microscopy, live cell imaging, digital image analysis and processing).