Dr Elizabeth Seward
Senior Lecturer (Placement Officer, Open Day Organizer)
Room: E03 Florey building
Brief career history
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.
Undergraduate and postgraduate taught modules
- Wajdner HE, Farrington J, Barnard C, Peachell PT, Schnackenberg CG, Marino JP, Xu X, Affleck K, Begg M & Seward EP (2017) 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
- Wareham KJ & Seward EP (2016) P2X7 receptors induce degranulation in human mast cells. Purinergic Signalling, 12(2), 235-246. View this article in WRRO
- Kay LJ, Gilbert M, Pullen N, Skerratt S, Farrington J, Seward EP & Peachell PT (2013) 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.