Dr. Gavin Davey
Associate Professor, Biochemistry
Associate Professor, Trinity Inst. of Neurosciences (TCIN)
Biography
My research interests are in the areas of Neuroscience and Glycobiology, with specific focus on enzymology, metabolic flux, glycosylation, computational & systems biology. My group researches the molecular and cellular mechanisms that underlie neurodegeneration in the brain, in particular, the role that energy metabolism and bioenergetics play in controlling neuronal function and dysfunction. A major goal is to understand how abnormal mitochondrial dynamics control cell loss in Parkinson's disease and other common brain disorders. My group also has interests in drug development and application of our technologies to the development of next-generation biotherapeutics, including bio- and glyco-engineering of recombinant proteins and therapeutic antibodies and nanoparticle synthesis for delivery of therapeutics into the brain.
Publications and Further Research Outputs
Peer-Reviewed Publications
Alice Pifferi, Elda Chiaino, Jesus Fernandez-Abascal, Aoife C. Bannon, Gavin P. Davey, Maria Frosini, and Massimo Valoti, Exploring the Regulation of Cytochrome P450 in SH-SY5Y Cells: Implications for the Onset of Neurodegenerative Diseases, Int. J. Mol. Sci, 25, 2024, p7439.-
Shanahan KA, Davis GM, Doran CG, Sugisawa R, Davey GP, Bowie AG., SARM1 regulates NAD+-linked metabolism and select immune genes in macrophages., The Journal of Biological Chemistry, 300, (2), 2024, p105620
Ryoichi Sugisawa, Katharine A. Shanahan, Gavin M. Davis, Gavin P. Davey, Andrew Bowie, SARM1 regulates pro-inflammatory cytokine expression in human monocytes by NADase-dependent and -independent mechanisms, iScience, 27, (6), 2024, p109940
Benevenuto SGM, Domenico MD, Yariwake VY, Dias CT, Mendes-da-Silva C, Alves NO, Caumo SEDS, Vasconcellos P, Morais DR, Cardoso MS, Ianicelli J, Waked D, Davey GP, Boylan F, Costa JL, Veras MM., Prenatal exposure to Cannabis smoke induces early and lasting damage to the brain., Neurochemistry International, 160, 2022
McDonald AG, Mariethoz J, Davey GP, Lisacek F., In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis., Scientific Reports, 27, (12(1)), 2022, p10846-
McDonald AG, Davey GP, O-Glycologue: A Formal-Language-Based Generator of O-Glycosylation Networks, Methods Mol Biol., 2370, 2021, p223 - 236
Hayes JM, O'Hara DM, Davey GP, Metabolic Labeling of Primary Neurons Using Carbohydrate Click Chemistry, Methods Mol Biol, 2021, p315 - 322
Dowling JK, Afzal R, Gearing LJ, Cervantes-Silva MP, Annett S, Davis GM, De Santi C, Assmann N, Dettmer K, Gough DJ, Bantug GR, Hamid FI, Nally FK, Duffy CP, Gorman AL, Liddicoat AM, Lavelle EC, Hess C, Oefner PJ, Finlay DK, Davey GP, Robson T, Curtis AM, Hertzog PJ, Williams BRG, McCoy CE , Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages, Nature Communications, 12, (1), 2021, p1460-
O'Farrell LK, Fraser AD, Davey GP, Monitoring the Sialome on Human Immune Cells , Methods Mol Biol, 2370, 2021, p323 - 329
McDonald AG and Davey GP , Simulating the enzymes of ganglioside biosynthesis with Glycologue, Beilstein Journal of Organic Chemistry , 2021
Smith J, Millán-Martín S, Mittermayr S, Hilborne V, Davey G, Polom K, Roviello F, Bones J., 2-Dimensional ultra-high performance liquid chromatography and DMT-MM derivatization paired with tandem mass spectrometry for comprehensive serum N-glycome characterization, Analytica Chimica Acta, 1179, (338840), 2021
Martignoni M; Benedetti M; Davey GP; Tipton KF; McDonald A, Degradation of thymic humoral factor
Kilbride, SM, Telford, JE and Davey, GP, Complex I controls mitochondrial and plasma membrane potentials in nerve terminals, Neurochemical Research, 2020
Vare lija D, Tipton KF, Davey GP, McDonald AG, 6-Hydroxydopamine: a far from simple neurotoxin., J Neural Transm, 2020
Abascal JF, Chiaino E, Frosini M, Davey GP, Valoti , β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration, International Journal of Molecular Sciences , 2020
Darren O'Hara, Gavin M. Davis, Natalie A. Adlesic, Jerrard M. Hayes and Gavin P. Davey, Dichloroacetate Stabilizes Mitochondrial Fusion Dynamics in Models of Neurodegeneration, frontiers in Molecular Neuroscience, 2019
Sinevici N, Mittermayer S, Davey GP, Bones J, O'Sullivan J, Salivary N-glycosyalation as a biomarker of Oral Cancer: A pilot study., Glycobiology, 2019
McDonald A.G., Tipton K.F. and Davey G.P., A mechanism for bistability in glycosylation, PLOS Computational Biology, 14, (8), 2018, pe1006348-
Djikic, T., Martí, Y., Spyrakis, F., (...), Schloss, P., Yelekci, K., Human dopamine transporter: the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities, Journal of Biomolecular Structure and Dynamics, 2018, p1-16
Hayes J.M, Wormald M.R, Rudd P.M, Davey G.P, Fc gamma receptors: Glycobiology and therapeutic prospects, Journal of Inflammation Research, 9, 2016, p209 - 219
McDonald AG, Tipton KF, Davey GP, A Knowledge-Based System for Display and Prediction of O-Glycosylation Network Behaviour in Response to Enzyme Knockouts., PLoS computational biology, 12, (4), 2016, pe1004844
McDonald AG, Hayes JM, Davey GP, Metabolic flux control in glycosylation., Current opinion in structural biology, 40, 2016, p97-103
Harte NP, Klyubin I, McCarthy EK, Min S, Garrahy SA, Xie Y, Davey GP, Boland JJ, Rowan MJ, Mok KH, Amyloid Oligomers and Mature Fibrils Prepared from an Innocuous Protein Cause Diverging Cellular Death Mechanisms., The Journal of biological chemistry, 290, (47), 2015, p28343 - 28352
Harte NP, Klyubin I, McCarthy EK, Min S, Garrahy SA, Xie Y, Davey GP, Boland JJ, Rowan MJ, Mok KH, Amyloid Oligomers and Mature Fibrils Prepared from an Innocuous Protein Cause Diverging Cellular Death Mechanisms, Journal of Biological Chemistry, 290, (47), 2015, p28343 - 28352
McDonald, A.G., Hayes, J.M., Bezak, T., Głuchowska, S.A., Cosgrave, E.F.J., Struwe, W.B., Stroop, C.J.M., Kok, H., van den Lar, T., Rudd, P.M., Tipton, K.F. and Davey, G.P., Galactosyltransferase 4 is a major control point for glycan branching in N-linked glycosylation, Journal of Cell Science, 127, 2014, p5014 - 5026
Hayes JM, Frostell A, Cosgrave EF, Struwe WB, Potter O, Davey GP, Karlsson R, Anneren C and Rudd PM , Fc gamma receptor glycosylation modulates the binding of IgG Glycoforms - a requirement for stable antibody interactions. , Journal of Proteome Research , (13), 2014, p5471 - 5485
Hayes JM, Cosgrave EF, Struwe WB, Wormald M, Davey GP, Jefferis R, Rudd PM, Glycosylation and Fc receptors., Current topics in microbiology and immunology, 382, 2014, p165-99
Davey, G.P., Bolaños, J.P., Peroxiredoxin 5 links mitochondrial redox signalling with calcium dynamics: Impact on Parkinson's disease, Journal of Neurochemistry, 125, (3), 2013, p332-333
Min S, Meehan J, Sullivan LM, Harte NP, Xie Y, Davey GP, Svanborg C, Brodkorb A, Mok KH, Alternatively folded proteins with unexpected beneficial functions., Biochemical Society transactions, 40, (4), 2012, p746-51
Artemenko, N.V., McDonald, A.G., Davey, G.P., Rudd, P.M., Databases and tools in glycobiology, Methods in Molecular Biology, 899, 2012, p325-350
Tipton KF, Davey GP, McDonald AG, Kinetic behavior and reversible inhibition of monoamine oxidases--enzymes that many want dead., International review of neurobiology, 100, 2011, p43-64
Burleigh SC, van de Laar T, Stroop CJ, van Grunsven WM, O'Donoghue N, Rudd PM, Davey GP, Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells., BMC biotechnology, 11, 2011, p95
Seán M Kilbride, Sonia A Gluchowska, Jayne E Telford, Catherine O'Sullivan and Gavin P Davey, High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal, Molecular Neurodegeneration , 6, (53), 2011
Simon J.R. Heales, Adrian Menzes, Gavin P. Davey, Depletion of glutathione does not affect electron transport chain complex activities in brain mitochondria: Implications for Parkinsons's disease and postmortem studies, Free Radical Biology and Medicine, 50, (7), 2011, p899-902
Telford, J.E., Kilbride, S.M., Davey, G.P., Decylubiquinone increases mitochondrial function in synaptosomes, Journal of Biological Chemistry, 285, (12), 2010, p8639-8645
McDonald, A.G., Tipton, K.F., Stroop, C.J., Davey G.P., GlycoForm and Glycologue: two software applications for the rapid construction and display of N-glycans from mammalian sources., BMC Research Notes, 18, (3), 2010, p1-7
Telford, JE, Kilbride SM and Davey GP, Complex I is rate limiting for oxygen consumption in the nerve terminal. , Journal Biological Chemistry, 284, 2009, p9109 - 9114
Nomenclature and Potential Functions of Copper Amine Oxidases in, editor(s)Giovanni Floris and Bruno Mondovi , Copper Amine Oxidases: Structures, Catalytic Mechanisms and Role in Pathophysiology, CRC Press, 2009, [S. Boyce, K. F. Tipton, M. I. O'Sullivan, G. P. Davey, M. Motherway Gildea, A. G. McDonald, A. Olivieri, and J. O'Sullivan]
Kilbride SM, Telford, JE, Tipton, KF and Davey GP, Partial inhibition of complex I activity increases Ca2+-independent glutamate release rates from synaptosomes. , Journal of Neurochemistry, 106, 2008, p826 - 834
Kilbride SM, Telford JE, Davey GP, Age-related changes in H2O2 production and bioenergetics in rat brain synaptosomes, Biochim Biophys Acta Bioenergetics, 1777, 2008, p783 - 788
Upadhyay R and Davey GP , Complex I and energy thresholds in the brain, Biochim Biophys Acta Bioenergetics, 1777, 2008, p777 - 782
J O'Sullivan, G Davey, M O'Sullivan, KF Tipton, Hydrogen peroxide derived from amine oxidation mediates the interaction between aminosugars and semicarbazide-sensitive amine oxidase, J Neural Transm, 2007
McDonald A, Tipton K, O'Sullivan J, Olivieri A, Davey GP, Coonan AM, Fu W, Modelling the roles of MAO and SSAO in glucose transport, Journal of Neural Transmission, 114, 2007, p783 - 786
Taurine, taurine analogues, and mitochondrial function and dysfuntion in, Taurine 6, 2006, pp469 - 479, [M Palmi, G Davey, KF Tipton, A Meini]
O'Sullivan J., O'Sullivan M.I., Tipton K.F. and Davey G.P. , Inhibition of amine oxidases by the histamine-1 receptor antagonist hydroxyzine, Journal of Neural Transmission, 71, 2006, p105 - 112
O'Sullivan J., Hernandez M., Unzeta M., Tipton K.F. and Davey G.P, Inhibition of semicarbazide sensitive sensitive amine oxidase and adhesion function. , Journal of Neural Transmission, 75, 2006, p105 - 112
Keith F Tipton, Gavin Davey, Martha Motherway, Monoamine oxidase assays, Current Protocols in Toxicology, 2006, p4.21.1 - 4.21.42
Tipton KF, Boyce S, O'Sullivan J., Davey G.P. and Healy J., Monoamine Oxidases: Certainties and Uncertanties, Current Med. Chemistry , 11, 2004, p1965 - 1982
Farmer MK, Tipton KF and Davey GP, The effects of two salsolinol derivatives on mitochondrial respiration and the likely nature of any endogenous parkinsonism-inducing toxin. In Monoamine Oxidase inhibitors and their role in neurotransmission, In Monoamine Oxidase inhibitors and their role in neurotransmission, 2004, p42 - 55
O'Sullivan J, Unzeta M, Healy J, O'Sullivan MI, Davey G, Tipton KF, Semicarbazide-sensitive amine oxidases: enzymes with quite a lot to do, Neurotoxicology, 25, 2004, p303 - 315
Tipton KF, O'Sullivan MI, Davey GP, O'Sullivan J, It can be a complicated life being an enzyme., Biochem Soc Trans, 31, 2003, p711 - 715
O'Sullivan J, O'Sullivan M, Tipton KF, Unzeta M, Del Mar Hernandez M, Davey GP, The inhibition of semicarbazide-sensitive amine oxidase by aminohexoses, Biochim Biophys Acta., 1647, (1-2), 2003, p367 - 371
Palmi M., Youmbi G., Sgaragli G.P., Meini A., Benocci A., Fusi F., Frosini M., Della Corte L., Davey G. P. and Tipton K.F., Advances in Experimental Medicine and Biology, 483, 2000, p87 - 96
Davey G.P. and Tipton K.F. , Mitochondria, Cell Death and DNA Damage, Radiation Research , (2), 2000, p390 - 394
Tipton K.F., Davey G.P. and Motherway M., Monoamine oxidase assays, Current Protocols in Pharmacology , (2), 1999, p3.61 - 3.6.42
Davey G.P., Peuchen S. and Clark J.B., Energy thresholds in brain mitochondria: potential involvement in neurodegeneration, Journal of Biological Chemistry , (273), 1998, p12753 - 12757
Davey G.P., Canevari L and Clark J.B. , Threshold effects in synaptosomal and nonsynaptic mitochondria from hippocampal CA1 and paramedian neocortex brain regions, Journal of Neurochemistry , (69), 1997, p2564 - 2570
Davey G.P. and Clark J.B, Control of oxidative phosphorylation in non-synaptic rat brain mitochondria. , Journal of Neurochemistry , (66), 1996, p1617 - 1624
Davey G.P. and Tipton K.F, Chronic ethanol consumption and mitochondrial sensitivity to 1-methyl-4-phenylpyridinium ion (MPP+) inhibition , Biogenic Amine, (12), 1996, p103 - 115
Bates TE, Strangward M, Keelan J, Davey GP, Munro PM, Clark JB., Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo, Neuroreport, 7, (8), 1996, p1397 - 400
Almeida A, Brooks KJ, Sammut I, Keelan J, Davey GP, Clark JB, Bates TE., Postnatal development of the complexes of the electron transport chain in synaptic mitochondria from rat brain, Dev Neurosci, 17, (4), 1995, p212 - 218
Davey G.P., Tipton K.F. and Murphy M.P. , Use of an electrode selective for 1-methyl-4-phenylpyridinium (MPP+) to measure its uptake and accumulation by mitochondria , Journal of Neural Transmission Suppl, (40), 1992, p47 - 45
Davey G.P., Tipton K.F. and Murphy M.P. , Uptake and accumulation of 1-methyl-4-phenylpyridinium by rat liver mitochondria measured using an ion-selective electrode, Biochemical Journal , (288), 1992, p439 - 443
Non-Peer-Reviewed Publications
McDonald AG and Davey GP, 'On/Off Switching During The Synthesis Of Complex Sugars', Science Trends, 2018, -
Reprogramming human dermal fibroblasts for the generation of pluripotent stem cells. in, editor(s)Freshney, R.I. , Culture of Animal Cells, a Manual of Basic Technique and Specialized Applications, John Wiley & Sons , 2010, [Sullivan S, Davey GP ]
McDonald AG, Tipton KF and Davey GP, Mathematical modelling of metabolism., The Biochemist, 2009
Research Expertise
Description
I am an enzymologist and my main research interests are in the areas of enzymology, metabolism, metabolic flux, glycosylation, computational & systems biology. My group researches the molecular and cellular mechanisms that underlie neurodegeneration in the brain, in particular, the role that energy metabolism and bioenergetics play in controlling neuronal function and dysfunction. I am internationally recognised as an expert in bioenergetics and metabolism and more recently in the rapidly expanding area of glycosylation research and glycobiology. A major goal is to understand how abnormal mitochondrial dynamics control cell loss in Parkinson's disease and other common brain disorders. My group also has interests in how mitochondria control immune cell metabolism and we have made some recent exciting high-impact discoveries in this area. I also have made substantial impact in drug development and application of our technologies to the development of next-generation biotherapeutics, including bio- and glyco-engineering of recombinant proteins and therapeutic antibodies. I have established myself among my peers as a researcher with a wide and deep understanding of mitochondria and metabolism by: 1. Discovering how mitochondrial dysfunction in neurons and the ageing brain controls neurodegeneration. I was the first to show that the mitochondrial complex I enzyme system is a major control point for controlling energy thresholds in brain nerve terminals. Through a series of high impact discoveries I am now recognised as an international leader in brain mitochondria research. 2. Showing that the use of flux control analysis and mathematical models of cellular metabolic networks reveal key metabolic control point in neurons, blood brain barrier epithelial cells and recently in immune cells. My advances in computational modelling of N- and O-linked glycosylation networks in cancer cells, immune cells and neurons has led to significant impact in the field of glycobiology and new collaborations with pharmaceutical companies. 3. Discovering how regulating glycosyltransferase enzyme activities can control the glycosylation status of recombinant biotherapeutics in CHO cell production systems. These discoveries have shown the field how to control glycan antennarity on proteins and also led to identification of optimal glycosylation routes for synthesis of human milk oligosaccharides. 4. Recently discovering how electron transport chain activities regulate energy production in immune cells and how this can control pro and anti-inflammatory effects. My expertise in mitochondrial biology has also been used to identify how the immunomodulatory protein SARM1 regulates mitochondrial function and subsequently macrophage cell activation.Projects
- Title
- Advanced Biopharmaceutical Technologies
- Summary
- Effect of extractables & leachables on CHO cell metabolism during single use bioprocessing.
- Funding Agency
- Science Foundation Ireland
- Date From
- 2014
- Date To
- 2017
- Title
- Training in neurodegeneration, therapeutics intervention and neurorepair
- Summary
- Research training of 12 PhD students
- Funding Agency
- EU Marie Curie
- Date From
- 2013
- Date To
- 2017
- Title
- Glycoengineering Fc/FcγR interactions
- Summary
- Investigation of cell surface glycosylation and glycan interactions that influence immune responses.
- Funding Agency
- Saudi Education Ministry
- Date From
- 2016
- Date To
- 2020
- Title
- What is the role for ACAD9 as a neurotherapeutic?
- Summary
- A PhD project investigation the role of ACAD9 on nerve terminal mitochondria function in the context of neurodegeneration.
- Funding Agency
- Irish Research Council
- Date From
- 2013
- Date To
- 2017
- Title
- Japan - Ireland International Strategic Cooperation Award
- Summary
- SFI funded student/academic exchange program with Japanese research institutions.
- Funding Agency
- Science Foundation Ireland
- Date From
- 2014
- Date To
- 2016
- Title
- Characterisation of Mitochondrial Proteins in Brain
- Summary
- Establishment of mitochondrial proteomics centre in the School of Biochemistry and Immunology.
- Funding Agency
- European Union
- Date From
- 2006
- Date To
- 2010
- Title
- Understanding glycosylation systems in the brain
- Summary
- An investigation of the dopamine cell surface glycome and regulation of bioenergetics in the context of Parkinson's disease
- Funding Agency
- Parkinson's Association of Ireland
- Date From
- 2010
- Date To
- 2011
- Title
- Glycan profiling in rheumatoid arthritis patients and biomarker development for MTX and anti-TNF non-responders
- Summary
- 2 PhD research projects investigating the metabolomics, bioenergetics and glycosylation status in PBMCs from RA patients.
- Funding Agency
- Croom Arthritis Research Charity
- Date From
- 2012
- Date To
- 2016
- Title
- Mitochondrial fusion dynamics in cancer cells and neurons
- Summary
- A PhD research project focussing on confocal imaging of mitochondrial dynamics in cancer cells and neurons
- Funding Agency
- Irish Research Council
- Date From
- 2007
- Date To
- 2010
- Title
- Computational Analysis of the Nerve Terminal
- Summary
- Systems Biology analysis of the nerve terminal in collaboration with Keith Tipton
- Funding Agency
- Science Foundation Ireland
- Date From
- 2002
- Date To
- 2006
- Title
- MITOTOX - Mitochondria and Toxicology
- Summary
- In vitro toxicology testing
- Funding Agency
- Enterprise Ireland
- Date From
- 2001
- Date To
- 2003
- Title
- Health Research Board Equipment Grant
- Funding Agency
- Health Research Board
- Date From
- 2000
Recognition
Representations
Member of University Council, Trinity College Dublin
Editor EBEC 2008 BBA Bioenergetics
Scientific Advisory Board NIBRT
Awards and Honours
Science Foundation Award Best Academia-Industry Collaboration Prize
Irish Pharma Awards - Best Industry-Academia Project
International Conference of Radiation Research conference lecture
European Union Marie Curie Return Grant
European Union Human Capital and Mobility Fellowship
Memberships
The Biochemical Society
The International Society for Neurochemistry
The American Society for Neurochemistry
Neuroscience Ireland