Cellular life must recognise and respond appropriately to diverse internal and external stimuli. By ensuring the correct expression of specific genes at the appropriate times, the transcriptional regulatory system plays a central role in controlling many biological processes: these range from cell cycle progression and maintenance of intracellular metabolic and physiological balance, to cellular differentiation and developmental time-courses. Numerous diseases result from a breakdown in the regulatory system and a third of human developmental disorders have been attributed to dysfunctional transcription factors (TFs). Furthermore, alterations in the activity and regulatory specificity of TFs are now established as major sources for species diversity and evolutionary adaptation. Indeed, increased sophistication of the regulatory system appears to have been a principal requirement for the emergence of metazoan life.
Much of our basic knowledge of transcriptional regulation has derived from molecular biological and genetic investigation. In the past decade, the availability of genome sequences and development of new laboratory techniques have generated (and continue to generate) information describing the function and organisation of regulatory systems on an unprecedented scale. Genomic studies now allow us to examine regulatory systems from a whole-organism perspective; on the other hand however, many observations made with these data are unexpected and appear to complicate our view of gene expression control.
The continued flood of biological data means that many interesting questions require the application of computational methods to answer them. The combination of computational biology and genomics enables us to uncover general principles that apply to many different biological systems; any unique features of individual systems can then be understood within this broader context.
My group pursues research dedicated to understanding on a genomic scale: (i) how gene expression is regulated and (ii) how this regulatory system controls biologically interesting phenomena. Much of our work until now has been purely computational, either analysing publicly available data or in collaboration with experimental laboratories performing functional genomic investigations.