Part of the research involves studying the molecular mechanisms of neurotransmitter release with the ultimate goal of deciphering the precise reactions and components that participate in this complex process. Such research will provide evidence that some of these components fail or work inappropriately in certain neuronal disorders including both neurodegenerative diseases and psychiatric illnesses. Recently a major study has convincingly proved that synaptic vesicles can exocytose by both a kiss-and-run and a full fusion mode, vesicles can switch from one mode to the other mode and that these modes are controlled by protein phosphorylation reactions, and intracellular calcium. Furthermore, both dynamin and myosin 2 have been shown to regulate these processes. The significance of these changes in biochemical release are to be assessed by electrophysiological recordings in conjunction with Philip Welsby.
During long term diabetes there is known to be a change in synaptic plasticity which leads to memory deficits. Recent research has investigated the differences between diabetic animals and control animals in terms of the mode of exocytosis. There is more of the kiss-and-run mode in diabetic animals which relates to the fact that upon stimulation there is a higher intracellular calcium level achieved in such diabetic terminals. This can be related to a switch in the type of voltage dependent calcium channel that is involved in coupling to neurotransmitter release. The group is currently trying to correlate the biochemical changes with distinct behavioural characteristics shown by control and diabetic animals that can be measured using a LABORAS animal behaviour system. This involves collaboration with Prof Jai Singh. Furthermore, future investigations of the changes in voltage dependent calcium channels will be studied using immune-fluorescence microscopy in conjunction with Chris Smith.
Other work carried out by Jai Singh involves the mechanism of stimulus-secretion coupling in the exocrine pancreas, the parotid salivary gland and the lacrimal glands. Mechanism of excitation-contraction coupling in the myocardium in normal and pathophysiological conditions (eg. Diabetes-induced cardiomyopathy, metabolic syndrome and hypomagnesemia). It is intended that future work will involve identification of molecular and neurochemical changes that underlie pathophysiological processes in behavioural pharmacology used to assess efficacy of novel compounds.
Dr Philip Welsby’s research interests focus on the central nervous system and include areas such as the treatment of dementia and brain tumours. With an expertise in electrophysiology he is investigating pharmacological approaches for the treatment of dementia by examining changes in synaptic plasticity, the molecular correlate of memory. These approaches include the selective targeting of cholinergic and histaminergic receptors and the characterisation of their signalling effects. Additionally, his interest in the treatment of glioma is examining the potential of aspirin analogues, work being done in collaboration with colleagues at Wolverhampton University, and also of asiatic acid where the focus is on novel drug delivery methods.
Chris Smith is a neuropharmacologist with an interest in pain and analgesia and in particular how sensory signals are processed within the spinal cord. Such spinal activity can change following nerve injury and give rise to clinical conditions with patients experiencing exaggerated pain and pain following normally non-painful stimuli. Chris currently has a project looking at invertebrate behavioural responses to external stimuli with a view to developing an analgesic screening model replicating this hypersensitivity that will reduce the need for vertebrate rodent models of pain.
Vicky Jones is a molecular neurobiologists with particular interests in the role of the ER in diseased states affecting neuronal and glial cells. She has utilised viral delivery systems to label the ER with fluorescent probes which has enable the morphology of the ER to be investigated in live cells. She has also looked at a triple knockout transgenic mouse model for Alzheimer’s disease and she is currently trying to make permanently transfected cell lines which also replicates the phenotype of the triple knockout mouse model.
Exocytosis and endocytosis
Transfection of neuronal cells
Immuno fluorescence microscopy
Chris Smith project 1: Developing an analgesic screening model by investigation invertebrate behavioural responses to external stimuli.
Dr Philip Welsby project 1: Effect of Chronic NSAID Treatment on Glioblastoma cell Proliferation
Dr Philip Welsby project 2: Effect of Chronic NSAID Treatment on Glioblastoma cell Apoptosis
Dr Vicky Jones project 1: Development of a super-photoactivatable fluorescent probe to reveal Endoplasmic Reticulum Dynamics in Glial cells
Dr Vicky Jones project 2: Investigation of the mechanisms underlying aberrant EGFR degradation in Glioblastoma
Prof Jai Singh project 1: Cellular, sub cellular and molecular mechanisms associated with cardiac remodelling in diabetic heart
Prof Jai Singh project 2: Beneficial effect of Momordica charantia, cinnamon, Glucagon-like peptide 1, Exenatide and exercise in the treatment of diabetes mellitus
Prof Jai Singh project 3: Mechanism of action of drugs and plant-based medicines in treating cancers.