Biomedical and Life Sciences

Lecturer

Office B33b
Division of Biomedical and Life Sciences
Faculty of Health and Medicine
Lancaster University
Lancaster
LA1 4YQ
UK

Tel: +44 1524 593561
Fax: +44 1524 593192
E-mail: r.lauder@lancaster.ac.uk

Research Interests

My research is focused on the elucidation of the structure and function of connective tissue macromolecules in health and disease. I have a special interest in the study of glycosaminoglycans (GAGs) and the proteoglycans (PGs) to which they are attached.

Glycosaminoglycans are a class of sulphated polysaccharides found in association with a protein core to form a PG. The structural diversity of GAGs is large and as novel systems are being examined and increasingly sensitive methods of detection and analysis are being used this diversity is expanding.

Important functionality is associated with GAGs and PGs and my work seeks to identify and examine these functions and their relationship with structural motifs especially within the GAG chondroitin / dermatan sulphate.

My work involves the development of GAG isolation and analysis methodologies and the application of these methods to several areas of investigation.

Development of methods for structural characterisation

The development of rapid and sensitive methods for the characterization of PGs and GAGs, based at present upon HPLC separation and fluorescent detection, is central to an increasing ability to identify novel structures and bio-functional motifs.

In addition, the development of novel methods for the fragmentation and isolation of PGs and GAGs allows an analytical focus to be placed upon specific motifs identified as having important roles.

Study of the age and disease related changes in structure

These enabling methodologies are being used to study the normal age related changes in PG and GAG structure within extracellular matrices, especially cartilage. With these baseline data in place a study of disease related changes, with a special focus upon osteoarthritis (OA), is now possible and this will be a major area of research development.

An understanding of the outcomes of the disease process will inform future work which will seek to understand the processes which are occurring during the progression of the disease. The aim will be to defer, preventing or reverse the progression of the disease, and, explore opportunities for early biochemical tests for the presence of the disease state.

Study of the structures of GAGs and PGs

I am also applying new and improved techniques for isolation and analysis to examine the GAGs and PGs from novel biological systems and to probe known systems with the expectation of isolating and identifying previously unidentified, rare, and potentially biologically important structures.

A knowledge of the spectrum of structures found in vivo will inform future work which seeks to elucidate the enzymes and mechanisms involved in their biosynthesis

Study of the functions of GAGs and PGs

I seek to elucidate the interactions and functions of PGs and GAGs. This work is informed by the strands of investigation described above; biologically active GAGs and PGs preparations can be identified, isolated, purified to homogeneity and characterised before being subject to interaction and functional studies.

For example, my previous work has established that the ability of Plasmodium falciparum infected red blood cells to bind to human placenta is modulated by two very specific structural motifs within chondroitin sulphate, one is required for binding but the other actively prevents, rather than simply failing to support, binding.

Selected Publications

1. Lauder, R. M. and Beynon, A. D. [1993] Unmasking and abolition of mineralising front sudanophilia. Biotechnic and Histochemistry 68: 180 - 185.
2. Huckerby, T. N., Dickenson, J., Tai, G. H., Lauder, R. M., Brown, G. M. and Nieduszynski, I. A. [1993] 13C NMR spectroscopy of keratan sulphates: Assignments for the reduced form of a repeat unit tetrasaccharide derived from keratan sulphate by a keratanase digestion and partial assignments for two fucosylated pentasaccharides. Mag. Reson. Chem. 31:394 - 398
3. Lauder, R. M., Huckerby, T. N. and Nieduszynski, I. A. [1994] The structure of the keratan sulphate attached to fibromodulin isolated from bovine tracheal cartilage, Oligosaccharides isolated following keratanase digestion. Biochem. J. 302: 417 - 423.
4. Lauder, R. M., Huckerby, T. N. and Nieduszynski, I. A. [1995] The structure of the keratan sulphate attached to fibromodulin isolated from bovine tracheal cartilage, Oligosaccharides isolated following keratanase II digestion. Glycoconjugate J. 12: 651 - 659.
5. Lauder, R. M., Huckerby, T. N. and Nieduszynski, I. A. [1996] The structure of the keratan sulphate attached to fibromodulin isolated from bovine articular cartilage. Eur. J. Biochem. 242: 402 - 409.
6. Lauder, R. M., Huckerby, T. N. and Nieduszynski, I. A. [1997] The structure of keratan sulphate chains from fibromodulin of human articular cartilage. Glycocongujate J. 14: 651 - 660
7. Lauder, R. M., Huckerby, T. N., Nieduszynski, I. A. and Plaas A. H. K. [1998] Age related changes in the structure of keratan sulphate chains isolated from bovine articular cartilage. Biochem. J. 330: 753-757.
8. Huckerby, T.N., Lauder, R. M. and Nieduszynski, I. A. [1998] Structural determination for octasaccharides derived from the carbohydrate-protein linkage region of chondroitin sulphate in aggrecan from bovine articular cartilage. Eur. J. Biochem. 258: 669-676.
9. Fried, M, Lauder, R. M. and Duffy, P. E. [1998] Minimal chondroitin sulphate structures required to support Plasmodium falciparum adhesion. Glycobiology. 8: 1021
10. Lauder, R. M., Huckerby, T. N. Nieduszynski, I. A. [1999] Isolation and identification of an octasaccharide chondroitin sulphate linkage region fragment. Carbohydrate Letters. 3: 381 - 388.
11. Lauder, R. M., Huckerby, T. N. and Nieduszynski, I. A. [2000] A high pH anion exchange chromatography fingerprinting method for chondroitin / dermatan sulphate and hyaluronan oligosaccharides. Glycobiology. 10: 393-401.
12. Lauder, R. M. [2000] Analysis of proteoglycans and glycosaminoglycans. In Encyclopaedia of Analytical Chemistry (Eds Myers, R., A. and Holyoake, A.) John Wiley. London.
13. Lauder, R. M., Huckerby, T. N. and Nieduszynski, I. A. [2000] Increased incidence of unsulphated and 4-sulphated residues in the chondroitin sulfate linkage region observed by high pH anion exchange chromatography. Biochem. J. 347: 339-348.
14. Huckerby, T.N. and Lauder, R. M. [2000] Keratan sulphates from bovine tracheal cartilage. Structural studies of intact polymer chains using ¹H and ¹³C-NMR spectroscopy. Eur. J. Biochem. 276: 3360-3369.
15. Lauder, R. M. [2000] Analysis of proteoglycans and glycosaminoglycans. In Encyclopaedia of Analytical Chemistry (Eds Myers, R., A. and Holyoake, A.) John Wiley. London.
16. Fried, M, Lauder, R. M. and Duffy, P. E. [2000] Plasmodium falciparum: Adhesion of placental isolates modulated by the sulfation characteristics of the glycosaminoglycan receptor. Experimental Parasitology. 95: 75-78.
17. Huckerby, T. N., Lauder, R. M., Brown, G. M., Nieduszynski, I. A., Anderson, K., Boocock, J. B., Sandell, P. L. and Weeks, S. D. [2001] Characterisation of oligosaccharides from the chondroitin sulphates: ¹H and ¹³C-NMR studies of di- and tetrasaccharides. Eur. J. Biochem. 268: 1181-1189.
18. Lauder, R. M., Brown, G. M., Bayliss, M. T., Huckerby, T. N. and Nieduszynski, I. A. [2001] Age related changes in the chondroitin sulphate linkage region of human articular cartilage aggrecan. Biochem. J. In the press.
19. Huckerby, T. N., Lauder, R. M. and Nieduszynski, I. A. [2001] Characterisation of oligosaccharides from the chondroitin sulphates: ¹H and ¹³C-NMR studies of tri- and hexa-saccharides. Eur. J. Biochem. In Preparation.
20. Lauder, R. M., Huckerby, T. N, Walker, C. and Sadler, I. [2001] Characterisation of oligosaccharides from the chondroitin / dermatan sulphates: ¹H and ¹³C-NMR studies of oligosaccharides generated by nitrous acid depolymerisation. Eur. J. Biochem. In Preparation.

ELECTRONIC PUBLICATIONS

1. Lauder, R. M. [1995] Proteoglycans and Glycosaminoglycans Home pages. A series of World Wide Web pages written and presented by R.M.Lauder as a section of the Glycoscience Interest Groups World Wide Web Pages. http://bssv01.lancs.ac.uk/gig/pages/toppage.htm
2. Lauder, R.M., Huckerby, T.N., Nieduszynski, I.A. [1997] Isolation and characterisation of octasaccharides derived from the linkage region of bovine articular cartilage chondroitin sulphate [Paper presented at the Third Electronic Glycoscience Conference]
3. Lauder, R.M. and Sansom, C. [1997] The Glycosciences Hyperglossary: Proteoglycans and Glycosaminoglycans [Paper presented at the Third Electronic Glycoscience Conference].
4. Lauder, R.M., Huckerby, T.N., Nieduszynski, I.A. [1996] The structure of keratan sulphate chains from fibromodulin of human articular cartilage. [Paper presented at the First Electronic Glycoscience Conference]
5. Lauder, R. M., Huckerby, T. N., and Nieduszynski, I. A. [1996] Age related changes in the structure of keratan sulphate chains isolated from bovine articular cartilage. [Paper presented at the First Electronic Glycoscience Conference]