Clive Bate
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Clive is currently a Lecturer for the PID department at the Royal Veterinary College. Clive’s primary research interest is in neurodegenerative diseases, specifically those caused following protein misfolding.
Biography
Clive completed a BSc in Pharmacology at Portsmouth University in 1988. He then went on to complete a PhD from UCL on the pathology of Malaria in 1991. He investigated the theory that cerebral malaria was due to a hyperactivity of the hosts’ immune system resulting in a “cytokine storm”.
From 1991 until the end of 1998 Clive worked at the Institute of Molecular Medicine in Oxford and the MRC unit, Fajara, The Gambia. From 1999 he joined Professor Alun Williams, first at Glasgow University Veterinary School and later moved to the RVC in the beginning of 2005 where he took his current post.
Research
Clive’s primary research interest is in neurodegenerative diseases, specifically those caused following protein misfolding (such as prion, Alzheimer’s and Parkinson’s diseases). Clive’s research encompasses 3 main themes. (1) The formation of prions within neuronal cells and how their formation can be blocked. (2) How the accumulation of misfolded proteins (either prions or the Aβ1-42 peptide that is thought to intiate pathogenesis in Alzheimer’s disease) causes damage to synapses (synaptotoxity) and ultimately neuronal death. The synapse damage represents the early stage of neurodegenerative disease. Clive’s research is aimed at stopping the synaptic destruction, and allowing the growth of synaptic connections. (3) The role of neuroinflammation, the responses of immune cells within the brain to cell damage, that occurs with Alzheimer’s and prion diseases.
Underlying these research interests is the concept that membrane biology and abnormal cell signaling pathways are important in the development of these diseases. Clive is particularly interested in the role of cholesterol in cell membranes and its effect specific “lipid raft” micro-domains, on cell signaling (phospholipase A2) and intracellular trafficking. These studies have identified a number of novel drugs that may be able to retard the progression of prion and Alzheimer’s disease.
Teaching
Clive lectures on prion and Alzheimer’s diseases to the BSc Bioveterinary Science course. He also lectures on parasitology, specifically how a parasite is successful and mechanisms of immune system evasion. He has also assisted with the BVetMed course and the Control of Infectious Disease MSc.
Selected Publications
Bate C, Tayebi M, Diomede L, Salmona M & Williams. A. (2009) Polyunsaturated fatty acids reduce prion-mediated synapse damage in vitro (Neurotoxicity Research - DOI 10.1007/s12640-009-9093-2).
Bate C, Tayebi M, Diomede L, Salmona M & Williams. A. (2008) Docosahexaenoic and eicosapentaenoic acids increase prion formation in neuronal cells. BMC Biology, 6. 139 (September).
Bate C & Williams A. (2008) Do prion-induced changes in cholesterol trigger neurodegeneration? Future Neurology 3 (4) 367-370.
BATE, C., TAYEBI, M. & WILLIAMS, A. (2008) Ginkgolides protect against amyloid-beta1-42-mediated synapse damage in vitro. Mol Neurodegener 3, 1. PubMed ID 18179689
BATE, C., TAYEBI, M. & WILLIAMS, A. (2008) Sequestration of free cholesterol in cell membranes by prions correlates with cytoplasmic phospholipase A2 activation. BMC Biol 6, 8. PubMed ID 18269734
BATE, C., TAYEBI, M. & WILLIAMS, A. (2008) Cholesterol esterification reduces the neurotoxicity of prions. Neuropharmacology 54, 1247-1253. PubMed ID 18448139
BATE, C., MARSHALL, V., COLOMBO, L., DIOMEDE, L., SALMONA, M. & WILLIAMS, A. (2008) Docosahexaenoic and eicosapentaenoic acids increase neuronal death in response to HuPrP82-146 and Abeta 1-42. Neuropharmacology 54, 934-943. PubMed ID 18355880
WILSON, R., BATE, C., BOSHUIZEN, R., WILLIAMS, A. & BREWER, J. (2007) Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide. BMC Neurosci 8, 99. PubMed ID 18034899
TAYEBI, M., BATE, C., HAWKE, S. & WILLIAMS, A. (2007) A role for B lymphocytes in anti-infective prion therapies? Expert Rev Anti Infect Ther 5, 631-638. PubMed ID 17678426
KEMPSTER, S., BATE, C. & WILLIAMS, A. (2007) Simvastatin treatment prolongs the survival of scrapie-infected mice. Neuroreport 18, 479-482. PubMed ID 17496807
BATE, C. & WILLIAMS, A. (2007) Squalestatin protects neurons and reduces the activation of cytoplasmic phospholipase A2 by Abeta(1-42). Neuropharmacology 53, 222-231. PubMed ID 17583757
BATE, C., RUMBOLD, L. & WILLIAMS, A. (2007) Cholesterol synthesis inhibitors protect against platelet-activating factor-induced neuronal damage. J Neuroinflammation 4, 5. PubMed ID 17233902
BATE, C., KEMPSTER, S. & WILLIAMS, A. (2006) Prostaglandin D2 mediates neuronal damage by amyloid-beta or prions which activates microglial cells. Neuropharmacology 50, 229-237. PubMed ID 16289250
BATE, C., KEMPSTER, S. & WILLIAMS, A. (2006) Platelet-activating factor antagonists protect amyloid-beta damaged neurons from microglia-mediated death. Neuropharmacology 51, 173-181. PubMed ID 16678220
BATE, C., KEMPSTER, S., LAST, V. & WILLIAMS, A. (2006) Interferon-gamma increases neuronal death in response to amyloid-beta1-42. J Neuroinflammation 3, 7. PubMed ID 16569229
BATE, C., BOSHUIZEN, R. & WILLIAMS, A. (2005) Microglial cells kill prion-damaged neurons in vitro by a CD14-dependent process. J Neuroimmunol 170, 62-70. PubMed ID 16225933
BATE, C. & WILLIAMS, A. (2004) Role of glycosylphosphatidylinositols in the activation of phospholipase A2 and the neurotoxicity of prions. J Gen Virol 85, 3797-3804. PubMed ID 15557253
BATE, C. & WILLIAMS, A. (2004) Detoxified lipopolysaccharide reduces microglial cell killing of prion-infected neurons. Neuroreport 15, 2765-2768. PubMed ID 15597050
BATE, C., VEERHUIS, R., EIKELENBOOM, P. & WILLIAMS, A. (2004) Microglia kill amyloid-beta1-42 damaged neurons by a CD14-dependent process. Neuroreport 15, 1427-1430. PubMed ID 15194867
BATE, C., SALMONA, M. & WILLIAMS, A. (2004) The role of platelet activating factor in prion and amyloid-beta neurotoxicity. Neuroreport 15, 509-513. PubMed ID 15094513
BATE, C., SALMONA, M. & WILLIAMS, A. (2004) Ginkgolide B inhibits the neurotoxicity of prions or amyloid-beta1-42. J Neuroinflammation 1, 4. PubMed ID 15285798
BATE, C., SALMONA, M., DIOMEDE, L. & WILLIAMS, A. (2004) Squalestatin cures prion-infected neurons and protects against prion neurotoxicity. J Biol Chem 279, 14983-14990. PubMed ID 14754889
BATE, C., REID, S. & WILLIAMS, A. (2004) Phospholipase A2 inhibitors or platelet-activating factor antagonists prevent prion replication. J Biol Chem 279, 36405-36411. PubMed ID 15210691
BATE, C., LANGEVELD, J. & WILLIAMS, A. (2004) Manipulation of PrPres production in scrapie-infected neuroblastoma cells. J Neurosci Methods 138, 217-223. PubMed ID 15325130
BATE, C., VEERHUIS, R., EIKELENBOOM, P. & WILLIAMS, A. (2003) Neurones treated with cyclo-oxygenase-1 inhibitors are resistant to amyloid-beta1-42. Neuroreport 14, 2099-2103. PubMed ID 14600505
BARRET, A., TAGLIAVINI, F., FORLONI, G., BATE, C., SALMONA, M., COLOMBO, L., DE LUIGI, A., LIMIDO, L., SUARDI, S., ROSSI, G., AUVRE, F., ADJOU, K. T., SALES, N., WILLIAMS, A., LASMEZAS, C. & DESLYS, J. P. (2003) Evaluation of quinacrine treatment for prion diseases. J Virol 77, 8462-8469. PubMed ID 12857915
EIKELENBOOM, P., BATE, C., VAN GOOL, W. A., HOOZEMANS, J. J., ROZEMULLER, J. M., VEERHUIS, R. & WILLIAMS, A. (2002) Neuroinflammation in Alzheimer's disease and prion disease. Glia 40, 232-239. PubMed ID 12379910
BATE, C., RUTHERFORD, S., GRAVENOR, M., REID, S. & WILLIAMS, A. (2002) Cyclo-oxygenase inhibitors protect against prion-induced neurotoxicity in vitro. Neuroreport 13, 1933-1938. PubMed ID 12395095
BATE, C., BOSHUIZEN, R. S., LANGEVELD, J. P. & WILLIAMS, A. (2002) Temporal and spatial relationship between the death of PrP-damaged neurones and microglial activation. Neuroreport 13, 1695-1700. PubMed ID 12352629
BATE, C., REID, S. & WILLIAMS, A. (2001) Killing of prion-damaged neurones by microglia. Neuroreport 12, 2589-2594. PubMed ID 11496154