Research Interests
Analytical Technology and Screening Research Group
One of the key steps in target-directed cancer drug discovery is the identification of small molecule compounds (hits) that inhibit the activity of validated target proteins. This can be achieved by high-throughput screening of large lead-like compound collections using appropriate biochemical and cell-based assay formats that report the activity of the drug target, or by screening small compound libraries of low molecular weight molecules (fragments) using very sensitive biophysical techniques and high concentration biochemical assays.
The role of the Analytical Technology and Screening group is to establish, validate and run high-throughput and fragment screens on selected cancer drug targets, and to carry out the initial characterisation of the hits obtained. Presently, we have a file of approximately 80,000 lead-like compounds and a fragment library of about 2,000 compounds. Once progressible compound series have been identified, the group is involved in supporting medicinal chemistry aimed at understanding and improving the pharmaceutical properties of the hits generated.
In addition, mechanistic endpoint assays are developed to support the Unit's drug discovery projects into clinical evaluation. These assays include, high-throughput phenotypic assays based on standard ELISA methodology and high content imaging assays based on the use of the InCell analyser.
Structure-Based Drug Design Research Group
The Structure-Based Drug Design Research Group is a joint initiative between the Divisions of Structural Biology and Cancer Therapeutics and consists of protein biochemists and protein crystallographers. The group has strong links with Medicinal Chemistry, In-Silico Medicinal Chemistry and Biology Teams within the CR-UK Cancer Therapeutics Unit and with the other crystallography team within the Division of Structural Biology.
We use biophysical techniques such as Tm-shift assays, Surface Plasmon Resonance, Isothermal Titration Calorimetry and High Throughput X-ray Crystallography to characterise protein-ligand interactions of hit matter resulting from our fragment and high-throughput screens and continue to investigate these interactions as the hits progress to advanced inhibitors.
In addition, we are responsible for the protein production for the biophysical characterisation and X-ray crystallography as well as for the biochemical assays carried out in the Analytical Technology and Screening Research Group. Therefore we are experienced in construct design and have our own E. coli and insect cell expression facilities and a modern protein purification laboratory.
