R. Jane Rylett
Chair and Professor
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PH.D. University of Western Ontario |
Research in my laboratory focuses on mechanisms regulating chemical communication in the nervous system in health, normal aging and disease. We are specifically interested in cholinergic neuron function. Cholinergic neurons projecting from basal forebrain nuclei to neocortex and hippocampus play important roles in cognitive processes such as learning and memory, while cholinergic neurons in striatum are involved in movement and motor functions. Degeneration of basal forebrain cholinergic neurons underlie a number of age-related neurological disorders such as Alzheimer disease and some of the cognitive deficits associated with normal aging. Dysfunction of cholinergic neurons in the striatum occurs in movement disorders such as Huntington's chorea, and imbalance between dopaminergic and cholinergic transmission is found in Parkinson's disease and drug-induced disorders such as tardive dyskinesia. Current research interests in my laboratory include the physiological mechanisms controlling events in the synthesis of the neurotransmitter acetylcholine, the role which growth and trophic factors may play in regulation of the expression of cholinergic neuronal phenotype and in maintenance and survival of these neurons, and the mechanisms by which amyloid peptides cause neuron dysfunction and degeneration. Other projects relate to identification and characterization of the neuronal choline transport protein, and investigation of regulation of activity of the transporter for delivery of choline as substrate for acetylcholine synthesis. A range of cellular and molecular biological approaches are used in these investigations, including genomics and proteomics, protein trafficking and molecular imaging, protein chemistry, protein-protein interactions and signal transduction.
Gill SK, Ishak M, Dobransky T, Haroutunian V, Davis KL, Rylett RJ (2006) 82-kDa choline acetyltransferase is in nuclei of cholinergic neurons in human CNS and altered in aging and Alzheimer disease. Neurobiology of Aging [Epub ahead of print] Kim AR, Dobransky T, Rylett RJ, Shilton BH (2005) Surface-entropy reduction used in the crystallization of human choline acetyltransferase. Acta Crystallographica D Biological Crystallography 61: 1306-1310. Dobransky T and Rylett RJ (2005) A model for dynamic regulation of choline acetyltransferase by phosphorylation. Journal of Neurochemistry 95: 305-313. Dobransky T, Doherty-Kirby A, Kim AR, Brewer D, Lajoie G, Rylett RJ (2004) Protein kinase C isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity. Journal of Biological Chemistry 279: 52059-52068. Gill SK, Bhattacharya M, Ferguson SS, Rylett RJ (2003) Identification of a novel nuclear localization signal common to 69- and 82-kDa human choline acetyltransferase. Journal of Biological Chemistry 278: 20217-20224. Kalisch BE, Demeris CS, Ishak M, Rylett RJ (2003) Modulation of nerve growth factor-induced activation of MAP kinase in PC12 cells by inhibitors of nitric oxide synthase. Journal of Neurochemistry 87: 1321-1332.
