My research lies in the field of bioinformatics, specifically in the area of protein sequence analysis. I maintain a database of protein fingerprints (PRINTS), which is accessible for searching via the Web and available for local installation via anonymous ftp. PRINTS is a companion resource to PROSITE, providing both a detailed annotation resource for protein families, and a diagnostic tool for newly-determined sequences (it therefore has particular relevance in the current drive to analyse, and functionally annotate, data from the various genome projects).
Central to my research is the provision of a diagnostic resource for G-protein-coupled receptors. For this diverse group of proteins, ~250 fingerprints have been designed, allowing us to distinguish receptors at the clan, superfamily, family and receptor subtype levels. Future detailed analyses will show whether it is possible to discriminate between receptors on the basis of the ligands they bind, or the particular G-proteins to which they couple.
Another important avenue of research is the investigation of methods to improve fingerprint diagnostic performance, with a view to identifying distant family relationships and penetrating deeper into the Twilight Zone (e.g., by explicit consideration of structural information and generating PRINTS-derived substitution matrices).
An essential aspect of the work involves manual manipulation of protein sequence alignments. To facilitate this process, we have developed a suite of visualisation tools called Utopia. The newest of the tools is Utopia Documents, a novel PDF reader that adds interactive functionality to static PDF articles. Utopia Documents powers the Semantic Biochemical Journal published by Portland Press Ltd.
Projects within the group include:
- Design of tools for linking research articles with their underlying data
- Analysis of functional motifs that distinguish GPCR subtypes
- Structural and functional analysis of kinases
- New approaches for sequence alignment
Research in my group involves using computers to analyse and understand biological information. Our focus is on the amino acid sequences of proteins, how these can be grouped into related families, and what these family relationships can tell us about protein function, structure and evolution. Members of a family in which we have a keen interest (G protein-coupled receptors) are acted upon by more than 50% of prescription drugs – this makes them especially interesting to pharmaceutical companies. We have developed an analysis method (protein fingerprinting) that allows us to uniquely diagnose new members of this and many other important families; it is used today in international projects to help annotate the results of newly-sequenced genomes. We are also interested in using computers to allow readers to make better use of scientific articles. In particular, we have developed software that ‘brings life’ to electronic versions of papers by adding interactive capabilities to them: e.g., by directly linking what is written with interactive software tools and online databases. The software (called Utopia) offers readers the best of both worlds – i.e., access both to the original research and to analysis tools that allow them to explore research findings in real time.