NEURODEGENERATION
Dr Gavin Davey
Dr Gavin Davey B.A.(Mod.),Ph.D.
Senior Lecturer in Neuroscience
Phone: + 353-1-896-8408/1853
Fax: + 353-1-6772400
Email: gdavey@tcd.ie
Location: Room 5.06,
Biomedical Sciences Institute
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Research Interests
The molecular and cellular mechanisms that underlie neurodegeneration in the brain are the main focus of research, in particular, the role that energy metabolism and bioenergetics play in controlling neuronal function and dysfunction. Cell reprogramming technologies are used to generate induced pluripotent stem (iPS) cell lines from mouse and human dermal fibroblasts. These cell lines are then differentiated into neurons that are used to study the biochemical mechanisms that control neurodegeneration.
Mitochondrial Energetics, Proteomics and the Permeability Transition Pore
The involvement of energy metabolism and mitochondrial dysfunction in the brain. The use of Metabolic Control Analysis Energy in studying energy thresholds in brain mitochondria. The involvement of mitochondria in cell death in the brain. The characterisation of the mitochondrial permeability transition pore in brain mitochondria and how pro-apoptotic or pro-necrotic signals may be released from mitochondria.
Cell Reprogramming and Induced Pluripotent Stem Cells
Using the latest reprogramming technologies, iPS cell lines are generated from disease-specific fibroblasts. Typically, fibroblasts are taken from patients with Parkinson’s disease, Alzheimer’s disease, Amytrophic Lateral Sclerosis, Huntington’s disease, Epilepsy and Schizophrenia, and reprogrammed using a mixture of reprogramming factors. Once stable iPS cell lines are generated, they are differentiated into neurons for biochemical characterization. These neurons are also used for drug discovery and toxicity screening.
Neurotoxins and Models of Parkinson’s disease
The actions of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a condition resembling Parkinson's disease: its metabolism, and the uptake and toxic effects of its metabolites. Mechanisms underlying the species differences in sensitivity to MPTP and the interactions of MPTP with drugs and alcohol. The behaviour of MPTP analogues. Biochemical mechanisms that underlie idiopathic Parkinson's disease and the clues that can be obtained from neurotoxin studies.
Production of Reactive Oxygen Species in Mitochondria from Adult and Aged Brain
Production of reactive oxygen species by the Electron Transport Chain in brain mitochondria. The mechanism in which superoxide radicals are produced during toxic insults and how they may cause lipid peroxidation and enzyme inactivation. The roles of oxidative enzymes, mitochondria and transition metals on oxidative tissue damage, apoptosis and necrosis.
Systems Biology and Mathematical Modelling
Using Systems Biology to understand and predict neurodegenerative events. Mathematical and computational analysis of the nerve terminal function. Computational modelling of glycosylation systems in CHO cells. Bioprocessing and biotechnology; glycosyltransferases and RNAi technology.
Research Personnel
Post Doctoral Fellow
Dr Eloy Cuadrado
Mitochondrial dynamics in reprogrammed neurons
Dr Tania O'Connor
Glycosyltransferases and recombinant protein production
Dr Andrew McDonald
Systems Biology & Glycosylation
Dr Ivo Fierro Monti
Characterisation of mitochondrial proteins in the brain
Dr Jerrard Hayes
Cell reprogramming and Parkinson's disease
Dr James Connolly
Molecular modelling & Parkinson's disease
Research Students
Susan Burleigh
Sialyltransferases and Glycosylation in CHO Cells
Sonia Gluchowska
Glycosyltransferases in CHO Cells
Darragh Crotty (Jointly with Prof. Mike Coey, School of Physics & CRANN)
Prevention of Degenerative Mechanisms in Neurons by Application of Strong Static and Low Frequency Magnetic Fields
Steven Quinn
Mitochondrial dynamics and Parkinson's disease
Emma Williams
Embryonic stem cells and Parkinson's disease
Laura Brady
Regulation of synaptic mitochondrial function and neurodegeneration
Visiting Socrates Students
Marc Pirson (University College Louvain)
Bioenergetics of synaptosomes
Marti Colom (University Pompeu Fabra, Barcelona)
Innate Immunity and Parkinson's disease
Louis Brisson (Montpellier SupAgro)
Reactive oxygen species and brain mitochondria
Financial Support
Enterprise Ireland (EI), Health Research Board ( HRB ), European Union (EU), Science Foundation of Ireland ( SFI ), IDA /National Institute of Bioprocessing Research and Training (NIBRT).
Academic Collaborations
Prof Keith Tipton, School of Biochemistry and Immunology, Trinity College Dublin, Ireland.
Prof Mercedes Unzeta, Department of Biochemistry, Autonomous University of Barcelona, Spain.
Dr Massimo Valoti, Department of Pharmacology, University of Siena, Italy.
Dr Simon Heales, Institute of Neurology, University College London, Queen Square, London, England
Prof Michael Coey, Department of Physics and CRANN, Trinity College Dublin, Ireland
Dr Patrick Schloss, Institute of Mental Health, Mannheim, Germany
Dr Padraig Fallon, School of Biochemistry and Immunology, Trinity College Dublin, Ireland.
Prof Rainer Pepperkok, European Molecular Biology Laboratory, Heidelberg, Germany
Prof Pauline Rudd, National Institute of Bioprocessing Research and Training (NIBRT) & Conway Institute, Belfield, Dublin, Ireland
Prof Orla Hardiman, Beaumont Hospital, Dublin, Ireland
Dr Colin Doherty, School of Medicine, St James Hospital, Dublin, Ireland
Dr Rashmi Upadhyar, Centre for Cellular and Molecular Biology, Hyderabad, India
Publications by the Neurodegeneration Group
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