NEUROCHEMISTRY, ENZYMOLOGY AND SYSTEMS BIOLOGY
Prof Keith Tipton
Keith Tipton, BSc, MA, PhD
Telephone: +353-1-896 1802
Fax: +353-1-677 2400
E-mail: ktipton@tcd.ie
Location: Room 1.1, Wellcome Building |
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Research Interests of the group
- Metabolism of neurotransmitters in the brain and the interactions of drugs with these processes.
- Enzyme behaviour, enzyme inhibition and enzymes with alternative functions.
- Systems biology.
- Enzymes and metabolic systems.
1. Neurochemistry
(i) Amine metabolism and drug interactions in the central nervous system and periphery. The behaviour of the enzymes of amine metabolism, their interactions with drugs that behave as antidepressants or neuroprotective agents. Optimal structure-function relationships of monoamine oxidase inhibitors. The mechanisms of the "cheese-reaction", and approaches to minimizing it. The functions and interactions of enzyme inhibitory drugs of potential value in the treatment of depression and Parkinson's disease. The interactions of ethanol and amine metabolism, with particular reference to the formation of alkaloids which may be involved in the addiction or tolerance processes.
(ii) The metabolism and function of taurine in the brain and periphery.
(iii) Production of reactive oxygen species (ROS) in brain. The roles of oxidative enzymes, mitochondria and transition metals on oxidative tissue damage, apoptosis and necrosis.
(iv) Excitatory amino acid neurotransmitters and excitotoxicity. The development and application of in vitro tests for excitotoxicity as potential models for ischaemic brain damage. The assessment of the mechanisms involved, the behaviour of different glutamate receptor subtypes and the effects of potential neuroprotective agents. The behaviour and function of enzymes involved in amino acid neurotransmitter metabolism.
2. Enzyme Behaviour
(i) Mechanisms through which the copper-containing amine oxidase (semicarbazide-sensitive amine oxidase; EC 1.4.3.6) also functions as a vascular-adhesion protein and modulates cellular glucose uptake.
(ii) Mechanisms of the complex behaviour shown by the oxidase reaction catalysed by peroxidase (EC 1.11.1.7).
(iii) The multiple functions of ceruloplasmin (ferroxidase; EC 1.16.3.1).
(iv) The behaviour and applications of suicide inhibitors and suicide substrates.
3. Systems Biology
Systems biology is the application of computational approaches to the understanding of the normal and dysfunctional behaviour of cellular systems.
Current projects include:
(i) Pathway tracing and metabolite connections.
(ii) Regulation of glucose transport in adipocytes and metabolism in normal and diabetic states.
(iii) Regulatory behaviour of branching processes.
(iv) Function and dysfunction of the aminergic nerve terminal.
(v) Complex dynamics and their biological significance.
The systems biology website is at http://www.systemsbiologyireland.org/
4. Enzyme Bioinformatics
We are responsible for curation of the International Union of Biochemistry and Molecular Biology's (IUBMB's) Enzyme List. This is a functional classification system in which novel enzymes are classified according to the reactions they catalyse, with each new enzyme being assigned an EC number. The work also involves updating entries for previously classified enzymes in the light of current knowledge. As the EC system is used extensively in many bioinformatics efforts, our group collaborates with many of the major world-wide bioinformatics centres, including the European Bioinformatics Institute, Cambridge (IntEnz), Kyoto University Bioinformatics Center (KEGG), University of Geneva (ExPASy and SWISS-PROT databases), University of Cologne (BRENDA database), University of Missouri at Columbia (KLOTHO database) as well as with IUBMB and IUPAC in this work.
International Union of Biochemistry and Molecular Biology (IUBMB)
Research Staff
Dr. Andrew McDonald
Systems Biology & Metabolic Bioinformatics
Dr. Jeff O'Sullivan
Semicarbazide Sensitive Amine Oxidases
Dr James Connolly
Computational approaches to the display and manipulation of metabolic pathways
Research Students
Laura Brady (Jointly with Dr. Gavin Davey)
Regulation of synaptic mitochondrial function and neurodegeneration.
WenHao Fu
Systems biological analysis of the synaptosome.
Susan Burleigh (Jointly with Dr. Gavin Davey)
Sialyltransferases and Glycosylation in CHO Cells
Visiting Research Students
Itziar Larrauri Vives, Socrates Student from Autonomous University Barcelona, Barcelona, Spain
Alessandra Carretta, University of Siena, Siena, Italy.
Raquel Folch Porta, Socrates Student from Autonomous University Barcelona, Barcelona, Spain.
Monica Vera Raez, Socrares Student from Automonous University Barcelona, Barcelona, Spain.
Francesca Fiorentino, Socrates Student from University of Florence, Italy.
Emma Williams, on studentship from SFI Ureka Supplement awards scheme.
Kira Holmstrom, on studentship from SFI Ureka Supplement awards scheme.
Financial Support
Enterprise Ireland (EI), Health Research Board (HRB), European Union (EU), National Institutes of Health (NIH), Science Foundation of Ireland (SFI) and the Pharmaceutical Industry.
Major Academic Collaborations
Dept. of Biochemistry, Autonomous University of Barcelona, Spain (Prof. Mercedes Unzeta)
Dept of Biochemistry, University of Cambridge, UK (Dr. Hal Dixon)
Dept of Biochemistry, University of Cologne, Germany (Prof. Dietmar Schomburg)
Dept of Biochemistry, University of Louvain-la-Neuve, Belgium (Prof. Robert Chrichton & Dr. Roberta Ward)
Dept. of Computer Science, University of Missouri, USA (Prof. Toni Kazic)
Dept of Pharmacology, University of Florence, Italy (Profs. Laura Della Corte & Laura Raimondi)
Dept of Pharmacology, University of Siena, Italy (Profs. Mitri Palmi, Giampietro Sgaragli & Massimo Valoti)
Dept of Pharmacology, University of Oxford, UK (Dr. J. Paul Bolam)
Dept of Pharmacology, Technion, Haifa, Israel (Prof. Moussa Youdin)
Dept of Pharmacology, University of Uppsala, Sweden (Prof. Lars Oreland)
European Bioinformatics Institute, Cambridge, UK (Dr. Rolf Apweiler)
Queen Mary University of London, UK (Dr. G.P. Moss)
Psychiatric Research Division, University of Saskatoon, Canada (Prof. Peter Yu)
Dublin Dental School (Dr. Michael O’Sullivan)
Plus collaborations with several other institutions under the ERASMUS and TEMPUS Schemes.
Recent Publications by the Neurochemistry, Enzymology and Systems Biology Group
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