Anne Dell

Division of Molecular Biosciences
Imperial College London

Anne Dell received a BSc degree in chemistry from the University of Western Australia in 1972 and then moved to the University Chemical Laboratory in Cambridge, UK, for her PhD studies. Under the supervision of Howard Morris she began her research career exploring the application of mass spectrometry to peptide sequencing. In 1975 she moved to a postdoctoral position in the Biochemistry Department at Imperial College in London where Howard Morris was establishing a biopolymer mass spectrometry research laboratory. This new facility was equipped with high field magnet instrumentation for high mass analysis, which was unique in the world. Collaborations with biochemists and biologists worldwide ensued, and led to Anne beginning her independent research career in the field of glycopolymer analysis by mass spectrometry. She rose through the ranks at Imperial College and was promoted to a Personal Chair in 1991. She was Head of the Biochemistry Department from 1999-2001 and now holds a prestigious Professorial Fellowship from the UK Biotechnology and Biological Sciences Research Council which is allowing her to focus full-time on research and related activities for five years.

For over twenty years Anne's laboratory has been at the forefront of the development of ultra-high sensitivity mass spectrometric procedures coupled with micro-chemical manipulations for the characterisation of complex carbohydrates and glycoconjugates of biological and medical importance. She has devised novel strategies for structurally characterising heterogeneous mixtures of glycans present in minute quantities in biological matrices and has applied these strategies to a wide range of biological problems via numerous collaborations with research groups around the world.

In the early 1980's Anne's group was the first to apply Fast Atom Bombardment Mass Spectrometry (FAB-MS) to glycopolymers, thereby solving a long-standing structural problem in mycobacterial polysaccharide research. Experience gained from this study led to the first precise structural assignments of biologically active oligosaccharides derived from plant cell walls (the so called "oligosaccharins"), and to the development of procedures for sequencing highly complex carbohydrates and for locating the many labile functional groups that are an integral part of many glycopolymers. In more recent years FAB methodology has been supplemented and surpassed by Matrix Assisted Laser Desorption Ionisation (MALDI) and Electrospray (ES) technologies and new chemical and enzymatic strategies have been devised to allow an ever increasing range of structural problems to be addressed.

A highly productive collaboration in the 1980's provided the first rigorous structural information on the polylactosaminoglycan-containing glycoproteins of human erythrocytes and leukocytes. This information was pivotal to rapid progress in defining possible ligands for the Selectins when they were cloned towards the end of the 1980's. A complementary study of leukocyte O-glycosylation provided vital information pertaining to the O-glycan biosynthetic pathways operating in these cells and laid the foundations for immunological and biochemical research into the roles of O-linked glycans in the immune system. Exploiting similar strategies to those employed in the aforementioned research, Anne went on to characterize a wide range of glycoproteins including murine zona pellucida glycoproteins, human uromodulin, the ovarian cancer marker CA125, and a variety of prokaryotic glycoproteins in organisms such as Campylobacter jejuni .

Other research highlights have included the characterisation of glycodelin A (GdA), a human endometrial glycoprotein with immunosuppressive and contraceptive activity, and GdS, a differently glycosylated form of glycodelin, which is found in human seminal fluid. Anne has also made significant contributions to the structural glycobiology of schistosomes and has pioneered the characterisation of nematode glycosylation, including the discovery of tyvelose containing lacdiNAc antennae in the immunodominant antigens of Trichinella spiralis , stage specific novel core fucosylation of Haemonchus contortus N-glycans, and unusual chito-oligomers in glycans from a filarial parasite. In recent years a major focus of Anne's work has been the development of high sensitivity strategies for defining the glycomes of tissues and cells. These methodologies are being employed in collaborative studies of knock-out mice and have been adopted by the Analytical Core of the Consortium for Functional Glycomics in its mouse and human glycomics programs.

Anne has received the Tate & Lyle and Haworth Medals of the Royal Society of Chemistry and the Roy L. Whistler Award of the International Carbohydrate Organisation and was Chair of the Glycobiology Gordon Conference in 2001. She was elected a Fellow of the Royal Society in 2002.

RESEARCH PROGRAMMES

My research is devoted to the development of ultra-high sensitivity mass spectrometric (MS) strategies and their application to biologically important structural problems in the field of glycobiology. A key objective is to provide the structural underpinning for national and international collaborative programmes of research which are aimed at defining the biological roles that carbohydrates play in health and disease. This work is supported by grants totalling from the BBSRC, the Wellcome Trust, the NIH and industry.

RECENT PUBLICATIONS:

MacFadyen JR, Haworth O, Robertson D, Hardie D, Webster MT, Morris HR, Panico M, Sutton-Smth M, Dell A , Van der Geer P, Wienke D, Buckley CD, & Isacke CM. “Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium”. FEBS Lett. 2005 May 9; 579 (12):2569-75 PMID: 15862292 [PubMed – in process]

Linton D, Dorrell N, Hitchen P, Amber S, Karlyshev AV, Morris HR, Dell A , Valvano MA, Aebi M & Wren BW. “Functional analysis of the Campylobacter jejuni N-linked protein glycosylation pathway”. Mol.Microbiol. 2005 Mar; 55(6):1695-703. PMID:15752194 [PubMed – in process]

Wilson JC, Hitchen PG, Frank M, Peak IR, Collins PM, Morris HR, Dell A , Grice ID. “ Identification of a capsular polysaccharide from Moraxella bovis.” Carbohydr Res. 2005 Mar 21;340(4):765-9. PMID: 15721351 [PubMed - in process]

Parry S, Sutton-Smith M, Heal P, Leir SH, Palmai-Pallag T, Morris HR, Hollingsworth MA, Dell A , Harris A.

“Evaluation of MUC6 mucin tandem repeats.” Biochim Biophys Acta. 2004 Dec 28; [Epub ahead of print]

Griffitts JS, Haslam SM, Yang T, Garczynski SF, Mulloy B, Morris H, Cremer PS, Dell A , Adang MJ,

Aroian RV. “Glycolipids as receptors for Bacillus thuringiensis crystal toxin.” Science. 2005 Feb 11;307(5711):922-5.

Feldman MF, Wacker M, Hernandez M, Hitchen PG, Marolda CL, Kowarik M, MorrisHR, Dell A , Valvano MA, Aebi M. “Engineering N-linked protein glycosylation with diverse O antigen lipopolysaccharide structures in Escherichia coli.” Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3016-21. Epub 2005 Feb 09 Leir SH, Parry S, Palmai-Pallag T, Evans J, Morris HR, Dell A , Harris A. “Mucin glycosylation and sulphation in airway epithelial cells is not influenced by CFTR expression.” Am J Respir Cell Mol Biol. 2005 Jan 27; [Epub ahead of print]

Kawar ZS, Haslam SM, Morris HR, Dell A , Cummings RD. “ Novel polyLacdiNAc and fucosylated polyLacdiNAc N-glycans from mammalian cells expressing beta 1,4-GalNAcT and alpha 1,3-FucT.”J Biol Chem. 2005 Jan 14;

Alvarez-Sanchez R, Divkovic M, Basketter D, Pease C, Panico M, Dell A , Morris H, Lepoittevin JP. (2004)

“ Effect of glutathione on the covalent binding of the 13C-labeled skin sensitizer 5-chloro-2-methylisothiazol-3-one to human serum albumin: identification of adducts by nuclear magnetic resonance, matrix-assisted laser desorption/ionization mass spectrometry, and nanoelectrospray tandem mass spectrometry.” Chem Res Toxicol. 2004 Sep;17(9):1280-8.