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I studied Chemical Physics at Bristol University and obtained a BSc (Hons) degree. Following that I became more interested in medical and biological topics obtaining an MSc in Medical Physics from the University of Aberdeen and a PhD in Biochemistry from University College London, in 1984. After working for a short time in industry, I worked as a postdoctoral research fellow at the National Institute of Medical Research until 1990. After that I joined the Department of Biochemistry and Molecular Biology at UCL and in 1995 I was awarded an MRC Senior Fellowship in Bioinformatics which has now been extended until 2005. In 2002 I was promoted to the position of Professor of Bioinformatics. My main research interests focus on bioinformatics which could be described as the theoretical analysis of genes, proteins and biological systems using computational methods. I have recently co-edited a textbook entitled Bioinformatics: Genes, Proteins and Computers which will be published by BIOS in 2003.
Research Interests
(1) Protein Structure Comparison, Classification and Analysis
During evolution protein structures are very conserved and sensitive structure comparison methods are therefore important for detecting evolutionary relationships. The challenge is to find mechanisms for representing the 3-D information which allow rapid but accurate identification of equivalent positions between two structures. Several algorithms have been developed which have enabled us to classify 40,000 known domain structures into evolutionary superfamilies in the CATH database. We are also designing methods to identify structural features associated with specific functional properties, conserved across a family of proteins. Ultimately, we would like to be able to predict the possible function of any gene sequence assigned to one of the protein families in our database.
CATH: A Hierarchic Classification of Protein Domain Structures.
C.A Orengo, A. D. Michie, D.T. Jones, M.B. Swindells & J.M.Thornton. Structure (1997), Vol 5, 1093-1108.
(2) Genome Annotation and the Analysis of Protein Functions and Biological Processes
Classification of proteins into families and superfamilies has allowed us to study the evolution of proteins in different kingdoms. For example, in enzyme families, although the chemistry tends to be well conserved, embellishments to the core of the structure, arising during evolution, can modify the substrate specificity. We have assigned genes from nearly 70 completed genomes to families and are now using this information to try to understand how the processes of domain duplication, domain modification, domain fusion have contributed to the evolution of new functions and biological processes.
Gene3D:Structural Assignments for Whole Genes and Genomes Using the CATH Domain Structure Database.
D. Buchan, D.Lee, J.Bray, F.Pearl, J.Thornton and C.Orengo (2002). Genome Res. Vol 12, 503-514.
The Evolution of Function in Protein Superfamilies.
A. Todd, C. Orengo, J.Thornton (2001). J. Mol. Biol. 307, 1113-1143.
(3) Functional Genomics and Datamining of Gene Expression Data
The new experimental technologies of functional genomics e.g. transcriptomics allow us to study the behaviour of large sets of proteins. For example transcriptomics can be used to study the expression of hundreds of genes during different biological conditions. We are developing datamining methods to help identify genes which are co-expressed because they are part of a common biological process. To do this we are designing a large data warehouse with special links between protein family, functional and gene expression data to glean further clues into the biological systems which have been activated.
Comparing, Contrasting and Combining Clusters in Viral Gene Expression Data, P.Kellam, X. Liu, N. Martin, C.Orengo, S. Swift and A.Tucker (2001) Proc of the Sixth Workshop on Intelligent Data Analysis in Medicine and Pharmacology, 56-62.
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