Dr Elizabeth Seward
School of Biosciences
Senior Lecturer
+44 114 222 2383
Full contact details
School of Biosciences
Firth Court
Western Bank
Sheffield
S10 2TN
- Profile
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- 2003- Present: Senior Lecturer, School of Biosciences, University of Sheffield, UK
- 2000-2003: Lecturer, Department of Cell Physiology & Pharmacology, University of Leicester, UK
- 1996-2000: Lecturer, Department of Pharmacology, University of Bristol, UK.
- 1994-1995: Postdoctoral Fellow, Glaxo Institute for Molecular Biology, Geneva, Switzerland.
- 1991-1994: Medical Research Council of Canada Postdoctoral Fellow, Dept Anatomy & Neurobiology, Medical College of Pennsylvania, Philadelphia, USA.
- 1991: Postdoctoral Researcher, Dept. Pharm., University of California, San Diego, USA
- 1986-1990: Ph.D. Department of Pharmacolgy, University of Cambridge, UK. Member of Trinity College.
- 1985: M. Phil. Department of Pharmacology, University of Cambridge, UK. Member of Trinity College.
- 1981-1984: B.Sc. (First Class Honours). Department of Biochemistry, McGill University, Montreal, Canada
- Research interests
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Aberrant secretion of neurotransmitters, hormones or immune mediators contributes to the pathology of a wide variety of chronic neurological, endocrine and inflammatory diseases ranging from stress and hypertension through to asthma and irritable bowel syndrome.
Research in our lab is focussed on identifying the signalling pathways and molecules controlling secretion from neurones and mast cells, with a special interest in voltage-gated (CaV), ligand-gated (P2X and nAChR), receptor-operated (TRPC) and store-operated (Orai) calcium channels, IgE and G protein coupled receptors (P2Y, Histamine), and SNARE regulatory proteins (synaptotagmins, Doc2 and Munc13).
Most of our work is performed at the level of isolated primary cells using high resolution techniques including patch-clamp electrophysiology, carbon fibre amperometry, calcium imaging and total internal reflection fluorescence microscopy with various fluorescence-based biosensors.
Recent highlights of our research include (1) the discovery of ATP-sensitive P2X receptors on human lung mast cells, activation of which may contribute to the pathophysiology of asthma, (2) the first demonstration of Munc13 as an essential effector of phospholipase C-coupled G protein coupled receptor regulation of neurotransmitter release in mammalian cells, and (3) the modulatory action of synaptotagmin IV on the calcium-sensitivity of the neuronal fusion machinery.
Regulated exocytosis and receptor signalling
Understanding the complex interplay between membrane receptors and the exocytotic machinery remains a fundamental unresolved question in cell biology. Regulated exocytosis involves the fusion of specialized vesicles with the plasma membrane and the ensuing secretion of chemical transmitters; it is the process most commonly used by cells to communicate with each other. Aberrant secretion contributes to the symptoms of a diverse group of diseases, ranging from metabolic disorders, cardiovascular disorders and neurological disorders to chronic inflammatory diseases.
G protein coupled receptors (GPCRs) represent the largest family of cell surface receptors in the human genome; in the nervous system they are part of a complex information processing system used to modulate neurotransmitter secretion and thereby co-ordinate the body’s response to changes in the external environment. An estimated 40% of marketed drugs target GPCRs, understanding the molecular mechanisms used by GPCRs to modulate neurotransmission is therefore an important area of neuroscience research and drug discovery programs.
Much knowledge has been gained over the last two decades about regulated exocytosis and the key molecules required for docking, priming and fusion of transmitter storing vesicles, but what is really lacking is an understanding of how these processes are modulated by cell surface receptors to fine tune secretory output.
Research in our lab is focused on identifying which signalling pathways are used by GPCRs to modulate secretion and, which molecules controlling exocytosis are targeted by these pathways.
We study exocytosis and receptor signalling using patch-clamp electrophysiology, amperometry, calcium imaging and high resolution fluorescent imaging in primary cells of neuronal and immune origin The results of our research provide insight into how receptor regulated modulation of exocytosis are altered in disease, and how this may be targeted to alleviate the symptoms of disease.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events. Cell Reports, 36(8).
- Secretion of mast cell inflammatory mediators is enhanced by CADM1-dependent adhesion to sensory neurons. Frontiers in Cellular Neuroscience, 13. View this article in WRRO
- Orai and TRPC channel characterization in FcεRI-mediated calcium signaling and mediator secretion in human mast cells.. Physiol Rep, 5(5). View this article in WRRO
- P2X7 receptors induce degranulation in human mast cells. Purinergic Signalling, 12(2), 235-246. View this article in WRRO
- Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE-dependent secretion from human lung mast cells. Clinical and Experimental Allergy, 43, 741-751.
All publications
Journal articles
- Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events. Cell Reports, 36(8).
- Double-binding botulinum molecule with reduced muscle paralysis: Evaluation in in vitro and in vivo models of migraine. Toxicon, 190, S5-S5.
- Porphyromonas gingivalis lipopolysaccharide rapidly activates trigeminal sensory neurons and may contribute to pulpal pain. International Endodontic Journal. View this article in WRRO
- Mast Cell Purification Protocols, 49-56.
- Secretion of mast cell inflammatory mediators is enhanced by CADM1-dependent adhesion to sensory neurons. Frontiers in Cellular Neuroscience, 13. View this article in WRRO
- Orai and TRPC channel characterization in FcεRI-mediated calcium signaling and mediator secretion in human mast cells.. Physiol Rep, 5(5). View this article in WRRO
- P2X7 receptors induce degranulation in human mast cells. Purinergic Signalling, 12(2), 235-246. View this article in WRRO
- Mast Cell Purification Protocols, 49-55.
- Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE-dependent secretion from human lung mast cells. Clinical and Experimental Allergy, 43, 741-751.
- Biophysical and Pharmacological Characterisation of Calcium Channels in Human Mast Cells. BIOPHYSICAL JOURNAL, 102(3), 425A-425A.
- Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses.. Nat Neurosci, 13(1), 45-52. View this article in WRRO
- Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells.. Br J Pharmacol, 157(7), 1215-1224.
- Functional transient receptor potential melastatin 7 channels are critical for human mast cell survival. J IMMUNOL, 179(6), 4045-4052.
- Differential regulation of endogenous N- and P/Q-type Ca2+ channel inactivation by Ca2+/calmodulin impacts on their ability to support exocytosis in chromaffin cells.. J Neurosci, 27(19), 5236-5248.
- Potentiation of exocytosis by phospholipase C-coupled G-protein-coupled receptors requires the priming protein Munc13-1.. J Neurosci, 27(1), 212-219.
- The fascinating and fleeting world of vesicle dynamics. Journal of Physiology, 585(3), 653-654.
- Identification of the P2Y(12) receptor in nucleotide inhibition of exocytosis from bovine chromaffin cells.. Mol Pharmacol, 66(3), 601-611.
- . Neurochemical Research, 27(11), 1371-1385.
- Bidirectional Modulation of Exocytosis by Angiotensin II Involves Multiple G-Protein-Regulated Transduction Pathways in Chromaffin Cells. The Journal of Neuroscience, 20(13), 4776-4785.
- Differential coupling between subtypes of voltage-operated Ca2+ channels and stimulus-evoked exocytosis in adult, bovine adrenal chromaffin cells. JOURNAL OF PHYSIOLOGY-LONDON, 523, 4P-5P.
- P2Y Purinoceptors Inhibit Exocytosis in Adrenal Chromaffin Cells via Modulation of Voltage-Operated Calcium Channels. The Journal of Neuroscience, 20(2), 606-616.
- G-protein coupled receptor stimulation of PLC, Ca2+and PKC increases the readily releasable pool of vesicles in chromaffin cells. EUROPEAN JOURNAL OF NEUROSCIENCE, 12, 18-18.
- Imaging Ca2+ concentration changes at the secretory vesicle surface with a recombinant targeted cameleon. Current Biology, 9(16).
- Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. British Journal of Pharmacology, 128(2), 479-485.
- Imaging Ca2+ concentration changes at the secretory vesicle surface with a recombinant targeted cameleon. Current Biology, 9(16), 915-S1.
- . Cellular and Molecular Neurobiology, 18(1), 65-80.
- Domains of P2X receptors involved in desensitization. Proceedings of the National Academy of Sciences, 93(26), 15485-15490.
- Functional selectivity of orphanin FQ for its receptor coexpressed with potassium channel subunits in Xenopus laevis oocytes. Molecular Pharmacology, 50(3), 447-450.
- Coexpression with potassium channel subunits used to clone the Y
2 receptor for neuropeptide Y. Molecular Pharmacology, 49(3), 387-390.
- Ba2+ ions evoke two kinetically distinct patterns of exocytosis in chromaffin cells, but not in neurohypophysial nerve terminals. The Journal of Neuroscience, 16(4), 1370-1379.
- Kinetics of stimulus-coupled secretion in dialyzed bovine chromaffin cells in response to trains of depolarizing pulses. The Journal of Neuroscience, 16(2), 553-562.
- Activation of nicotinic receptors triggers exocytosis from bovine chromaffin cells in the absence of membrane depolarization.. Proceedings of the National Academy of Sciences, 92(7), 3065-3069.
- Exocytosis in peptidergic nerve terminals exhibits two calcium- sensitive phases during pulsatile calcium entry. The Journal of Neuroscience, 15(5), 3390-3399.
- Chromaffin cell cortical actin network dynamics control the size of the release-ready vesicle pool and the initial rate of exocytosis. Neuron, 14(2), 353-363.
- μ-Opioid-receptor-mediated inhibidon of the N-type calcium-channel current. Proceedings of the Royal Society of London. Series B: Biological Sciences, 244(1310), 129-135.
- Characterization of two components of the N-like, high-threshold-activated calcium channel current in differentiated SH-SY5Y cells. Pfl�gers Archiv European Journal of Physiology, 417(2), 223-230.
- Epileptogenic action of penicillin derivatives: structure-activity relationship. Neuropharmacology, 24(6), 571-575.
- A sensitive cell-based assay for testing potency of Botulinum neurotoxin type A. ALTEX.
- Double-Binding Botulinum Molecule with Reduced Muscle Paralysis: Evaluation in In Vitro and In Vivo Models of Migraine. Neurotherapeutics.
Chapters
- Membrane Capacitance Measurements of Stimulus-Evoked Exocytosis in Adrenal Chromaffin Cells, Methods in Molecular Biology (pp. 187-202). Springer US
Conference proceedings papers
- Orai and TRPC Channel Contribution to Calcium Signaling in Human Mast Cells. BIOPHYSICAL JOURNAL, Vol. 106(2) (pp 317A-317A)
- The Role of Doc2B in Depolarization-Evoked and G Protein-Coupled Receptor Modulated Exocytosis in Mouse Chromaffin Cells. BIOPHYSICAL JOURNAL, Vol. 106(2) (pp 312A-312A)
- Expression of TRPM7 and TRPM2 channels in human lung mast. THORAX, Vol. 60 (pp II120-II120)
- Selective inhibition of rapid exocytosis from adrenal chromaffin cells by adenoviral expression of a mutant calmodulin. BIOPHYSICAL JOURNAL, Vol. 88(1) (pp 262A-262A)
- Identification of a TRPM7-like cation channel in human lung mast cells. THORAX, Vol. 59(1) (pp 27-28)
- Calmodulin Regulation of Calcium Channels in bovine adrenal chromaffin cells. BIOPHYSICAL JOURNAL, Vol. 86(1) (pp 275A-275A)
- Induction of tolerance to the inhibitory effect of mu opioid receptor agonists on the calcium current in human neuroblastoma SH-SY5Y cells. New leads in opioid research: proceedings of the International Narcotics Research Conference. ICS914 (pp 302)
Preprints
- Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events. Cell Reports, 36(8).
- Research group
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Collaborators
- Dr Walter Marcotti
- Dr Peter Peachell
- Dr Heather Wilson
- Prof G Battaglia
- Prof D Grundy
- Prof Peter Bradding (University of Leicester, UK)
Postgraduate studentship opportunities
We advertise PhD opportunities (Funded or Self-Funded) on FindAPhD.com
- Grants
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- Wellcome Trust
- HEFCE
- GSK
- AZ
- BBSRC
- Teaching activities
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Undergraduate:
- BMS109-108 Physiology with Pharmacology (Coordinator)
- BMS242/245 Phys Pharm Cells
- BMS242/243 Core Phys Pharm
- BMS301 Membrane Receptors (Coordinator)
- BMS376 Membrane Trafficking
- Level 3 Practical and Dissertation Modules
Masters (MSc):
- BMS6061 Membrane Receptors (Coordinator)
- Professional activities and memberships
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Member of:
- Asthma UK Research Review Panel Member
- International Symposium on Chromaffin Cell Biology Organizing Committee (2005-)
- Biophysical Society, Exocytosis and Endocytosis Subgroup (2002-)
- Society for Neuroscience (1991-)
- Physiological Society (1999-)