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EBIGroupsLuscombe GroupResearch

Luscombe Group Research Interests

A summary of our research interest:



Introduction


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 development disorders have been attributed to dysfunctional transcription factors. Further, alterations in the activity and regulatory specificity of transcription factors are now established as major sources for species diversity and evolutionary adaptation. Indeed, increased sophistication in the regulatory system appears to have been a principal requirement for the emergence of metazoan life.

Much of our basic knowledge of transcription regulation has derived from molecular biological and genetic investigations. In the past decade, the availability of genome sequences and development of new laboratory techniques have (and continue to) generate information describing the function and organisation of regulatory systems on an unprecedented scale. Genome-scale studies now allow us to examine the regulatory system from a whole-organism perspective; on the other hand however, observations made with these data are often unexpected and appear to complicate our view of gene expression control.

This continued flood of biological data means that many interesting questions require the application of computational methods to answer them. The strength of bioinformatics is its ability to uncover general principles providing global descriptions of entire systems. Armed with these biological data we are now in a great position to do this.

Much of our work so far focused on the regulatory system in the yeast Saccharomyces cerevisiae: by integrating diverse data sources – from genome sequence to the results of functional genomics experiments – we can study the regulatory system at a whole-organism level (Figure 1). We are now also expanding our interests to regulatory processes in enterobacteria and humans.
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Current work


Our current projects include:
  • Developing Graphical Models approaches to integrate disparate data sources and provide a probabilistic framework for understanding the relationship of regulatory network structure to its function.

  • Studying the structure and robustness of the regulatory network to identify regions of vulnerability that have potential implications for diseases.

  • Examining how the transcriptional regulatory network interacts with other cellular components such as the metabolic system.

  • Analysing the repertoire, usage and cross-species conservation of transcription factors in the human genome.

  • Wet/dry lab collaborations to uncover the regulation governing complex bacterial behaviour.
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Collaborations


We collaborate extensively with experimental research groups in Cambridge and Heidelberg (see 'people page' for details). We also interact regularly with a number of groups within the EBI, namely the Thornton, Huber, Bertone and the Microarray Informatics groups.
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Future work


We will continue advancing analysis techniques and our understanding of regulatory systems in relatively simple organisms such as yeast. We will also consolidate our work with the regulatory apparatus in bacteria and mammalian organisms. A major focus continues to be our close interactions with research groups performing genome-scale experiments.







































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