Dr Elizabeth Seward
School of Biosciences
Senior Lecturer
+44 114 222 2383
Full contact details
School of Biosciences
Firth Court
Western Bank
ºù«Ӱҵ
S10 2TN
- Profile
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- 2003- Present: Senior Lecturer, School of Biosciences, University of ºù«Ӱҵ, 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
- . Cell Reports, 36(8).
- . Frontiers in Cellular Neuroscience, 13.
- . Physiol Rep, 5(5).
- . Purinergic Signalling, 12(2), 235-246.
- . Clinical and Experimental Allergy, 43, 741-751.
All publications
Journal articles
- . Cell Reports, 36(8).
- . Toxicon, 190, S5-S5.
- . International Endodontic Journal.
- , 49-56.
- . Frontiers in Cellular Neuroscience, 13.
- . Physiol Rep, 5(5).
- . Purinergic Signalling, 12(2), 235-246.
- , 49-55.
- . Clinical and Experimental Allergy, 43, 741-751.
- . BIOPHYSICAL JOURNAL, 102(3), 425A-425A.
- . Nat Neurosci, 13(1), 45-52.
- . 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.
- . J Neurosci, 27(19), 5236-5248.
- . J Neurosci, 27(1), 212-219.
- . Journal of Physiology, 585(3), 653-654.
- . Mol Pharmacol, 66(3), 601-611.
- . Neurochemical Research, 27(11), 1371-1385.
- . 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.
- . 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).
- . British Journal of Pharmacology, 128(2), 479-485.
- . Current Biology, 9(16), 915-S1.
- . Cellular and Molecular Neurobiology, 18(1), 65-80.
- . 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.
- . The Journal of Neuroscience, 16(4), 1370-1379.
- . The Journal of Neuroscience, 16(2), 553-562.
- . Proceedings of the National Academy of Sciences, 92(7), 3065-3069.
- . The Journal of Neuroscience, 15(5), 3390-3399.
- . Neuron, 14(2), 353-363.
- . Proceedings of the Royal Society of London. Series B: Biological Sciences, 244(1310), 129-135.
- . Pfl�gers Archiv European Journal of Physiology, 417(2), 223-230.
- . Neuropharmacology, 24(6), 571-575.
- . ALTEX.
- . Neurotherapeutics.
Chapters
- , Methods in Molecular Biology (pp. 187-202). Springer US
Conference proceedings papers
- . BIOPHYSICAL JOURNAL, Vol. 106(2) (pp 317A-317A)
- . 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
- .
- . 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-)