The group has had a long term interest in the development of special techniques for the purification of very low levels of biochemicals (e.g. proteins, peptides, prostoglandins, lipids) present in biological samples at trace levels. We use these purified compounds to understand both their structure (shape) and function (biological activity).

We have also been involved in the development of sensitive biosensor techniques, in which we couple the exquisite sensitivity of biological interactions with sensitive physico-chemical and chemical methods of detection in instrumental devises, for measuring protein-protein interactions. The sensitivity of many modern analytical systems means that we can now recover sufficient material from the biosensor surfaces for detailed characterization (proteomics analysis).

We have developed automated medium-throughput cell-based bioassays to support these purification protocols and structure-function studies and can use then to identify stimulants (agonists) and inhibitors (antagonists) of key biochemical pathways. Importantly, these systems have been typically applied to identify and characterise proteins and signalling pathways involved in cancer development and progression, with a view to using this information to develop new anti-cancer drugs or sensitive and specific assays for the detection and monitoring of cancer.

Major on-going projects include the development of novel biosensor platforms for the analysis of telomerase in clinical samples from patients with colon and bladder cancer, development of a new generic biosensor platform for the amplified detection of protein biomarkers and the validation of EGFR-based assays for monitoring of patients with colon cancer.

Additionally, a panel of colon cancer biomarker assays are being developed and validated as part of The Human Colon Cancer Initiative. We are also developing affinity-based proteomics methods for the analysis of protein-complexes including the Wnt-APC-βcatenin, E-cadherin, A33 and EGFR signalling pathways, and have recently extended this to allow for comparative analysis of signalling pathways following in situ phosphorylation.

As part of our studies on the development of new therapeutic reagents we have recently established a Pharmacokinetices Team who are using a range of chemical and biochemical techniques to monitor drug pharmacokinetics and metabolites in preclinical studies. Finally we have produced and characterised a number of reagents to further our understanding of the role of laminin-10/integrin/EGFR signalling in the potentiation of colon cancer metastasis.

1. E.C.Nice and B.Catimel, Instrumental biosensors: New perspectives for the analysis of biomolecular interactions. Bioessays, 21, 339 – 351, 1999

2. T. Domagala, N. Konstantopoulos, F. Smyth, R.N. Jorissen, L.Fabri, D. Geleick, I.Lax, J.Schlessinger, W.Sawyer, G.J.Howlett, A.W. Burgess and E.C. Nice. Stoichiometry, Kinetic and Binding Analysis of the Interaction between Epidermal Growth Factor (EGF) and the Extracellular Domain of the EGF Receptor. Growth Factors, 18, 11 – 29, 2000

3. AG Ellis, MM Doherty, F.Walker, J.Weinstock, M.Nerrie, A.Vitali, R.Murphy, R.Luwor, T.Johns, A.Scott, A.Levitzki, G.McLachlan, L.Webster, AW Burgess and E.Nice. Preclinical studies on the tissue distribution and pharmacokinetics of the analinoquinazoline AG1478, a specific small molecule inhibitor of EGFR tyrosine kinase, Biochem. Pharmacol. 71, 1422-34, 2006

4. B. Catimel, J. Rothacker, J. Catimel, M.Faux, J. Ross, L.Connolly, A. Clippingdale, A.W.Burgess and E. Nice. Biosensor-based micro-affinity purification for the proteomic analysis of protein complexes. J.Proteome. Res. 4, 1646 – 1656, 2005