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Biological Chemistry and Lipid Research

The main emphasis of the Laboratory of Biological Chemistry and Lipid Research
has been on the study of biochemical pathways and molecular mechanism of action of small molecules. Bioactive lipids such as the polyunsaturated fatty acids (PUFA), eicosanoids, resolvins and other novel bioactive lipid mediators form a core research theme within the laboratory, whilst other projects deal with the biochemistry of sulphur amino acids such as homocysteine and glutathione, and bile salts.

The_Structural_Diversity_of_Lipids.pdf

Lipidomics is a research field dedicated to the understanding of lipid function through the complete qualitative and quantitative analysis and profiling of lipid species, elucidation of lipid-lipid and lipid-protein interactions, and lipid-mediated signalling networks in biological systems. Lipidomics may be further extended to include the genomics and biosynthetic pathways of lipid metabolism, normal and abnormal functions of lipids, biological membranes, and proteins that interact and metabolise lipids, contributing thus significantly to biomedical research and drug development. Within this context we have developed mass spectrometry-based assays for membrane phospholipids (structural lipidomics) and a range of bioactive lipid mediators (mediator lipidomics) such as the eicosanoids. This multidisciplinary approach is supported by metabolite analysis and profiling by high-field NMR, HPLC, MS/MS and LC/MS, GC, organic synthesis, protein chemistry and enzymology.

Mediator_lipidomics,_eicosanoids.pdf

Structural_lipidomics_one_step_analysis_of_membrane_phospholipids.pdf

Current projects focus on the molecular mechanism of action of polyunsaturated fatty acids and their role in brain function and neuroinflammation, the production of eicosanoids by skin cells and its significance in the sunburn response in human skin, the function of eicosanoids in the reproductive and cardiovascular systems, and cancer development, sulphur amino acid kinetics and oxidative damage, and the study of methionine dependence as chemotherapeutic target.

Sulfur_amino_acid_mediated_pathways.pdf

Contact details
Group Leader: Prof A. Nicolaou
School of Pharmacy, University of Bradford, Bradford BD7 1DP
Email: : Tel: 44(0)1274 234717; Fax: 44(0)1274 235600

Lab Members
Dr G Syoun (Research Assistant)
Ms M Massodi (Research Assistant)
Ms K Massey (Research Assistant )
Mr A Healey (Research Technician, Mass Spectrometry Support)
Ms A Williams (Postgraduate student)
Ms A Shrinivasan (Postgraduate student)
Ms N Anyakoha (Postgraduate student)
Ms J Durn (Postgraduate student)
Mr K Kedhil (Postgraduate student)
Mr H Elsihawi (Postgraduate student)
Mr AA Mir (Postgraduate student)

Our Sponsors

*The Wellcome Trust

*MRC

*BBSRC

*YCR

*The Royal Society

*The Pancreatic Society

*Yorkshire Forward

*Amarin Neuroscience

*PZ Cussons

*Allergan

Selected Recent Publications

SH Rahman, AR Srinivasan, A Nicolaou. Defects in the transulfuration pathway and increased glutathione degradation contribute to oxidative stress associated with severe acute pancreatitis (2008) Dig Dis Sci, in press

RM Clarke, A Lyons, F O’Connell, BF Deighan, CE Barry, NG Anyakoha, A Nicolaou, MA Lynch. A pivotal role for interleuking-4 in atorvastatin-associated neuroprotection in rat brain. (2008) J Biol Chem 283, 1808-1817

M Masoodi, AA Mir, NA Petasis, SN Serhan, A Nicolaou. Simultaneous lipidomic analysis of three families of bioactive lipid mediators leukotrienes, resolvins, protectins and related hydroxy-fatty acids by liquid chromatography/electrospray tandem mass spectrometry (2008) Rapid Commun Mass Spectrom 22, 75-83

SJ Little, MA Lynch, MS Manku, A. Nicolaou. Lipidomic analysis reveals docosahexaenoic acid-induced alterations in the phospholipid profiles of young and aged cortical tissue (2007) Prost Leuk Essen Fatty Acids 77, 155-162

E Banks, S Doughty, RT Wheelhouse, A Nicolaou. Inhibition of the cobalamine-dependent methionine synthase by substituted benzo-heterocycles (2007) FEBS J 274; 287-299

M Masoodi and A Nicolaou. Lipidomic analysis of twenty seven prostanoids and isoprostanes by electrospray liquid chromatography/tandem mass spectrometry (2006) Rapid Commun Mass Spectrom 20; 3023-3029

V Pavillard, A Nicolaou, JA Double, RM Phillips. Methionine dependence of tumours: A biochemical strategy for optimising paclitaxel chemosensitivity in vitro (2006) Biochem Pharmacol 71; 772-778

A Nicolaou and YH Peng. Lipidomics: current developments, challenges and opportunities. (2006) Lipid Technology 18(3); 53-57

DC Rees, A Iolascon, M Carella, AS O’Marcaigh, JR Kendra, SN Jowitt, JK Wales, A Vora, M Makris, N Manning, A Nicolaou, J Fisher, A Mann, SJ Machin, PT Clayton, P Gasparini, GW Stewart. Stomatocytic haemolysis and macrothrombocytopenia is the haematological presentation of phytosterolaemia. (2005) Br J Haematol 130; 297-309

A Blackburn, M Bibby, M Lucock, A Nicolaou. Temporal evaluation of methionine synthase and related metabolites in the MAC15A mouse adenocarcinoma animal model (2004) Inter J Cancer 112; 577-584

A Nicolaou, SE Estdale, M Tsatmali, DP Herrero, AJ Thody. Prostaglandin production by melanocytic cells and the effect of alpha -melanocyte stimulating hormone (2004) FEBS Letts 570 223-226

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