Nicholas Luscombe

Bioinformatics and Computational Biology Laboratory

The Luscombe group's research focuses on the analysis of genomic data using bioinformatic and computational methods.

In particular, we study how the biology of an organism is shaped by regulation of gene expression. We investigate this at various levels of complexity, from single-celled bacteria and yeast to complex mammals. Expression of a gene - i.e. production of a protein - is a complex exercise requiring large, gluttonous protein machines which expend the cell's energy reserves. Hence, the organism needs to be judicious in choosing which proteins to produce when and where. Furthermore, the expression of all genes at all times would be detrimental to the organism. Expression must be rigourously regulated so that the right genes are 'switched on or off' in response to changes in the internal and external environments of the cell.

The question of 'when to produce' is the only issue in bacteria, which consist of a single cell. The bacterial cell comes under a variety of stresses to which it must rapidly adapt in order to survive. The control of not only 'when' but also 'where' is crucial in mammals. All tissue types in the human body carry the same set of genes; yet, they are different from one another. This is because different subsets of genes are expressed in different tissues.

While decisions relating to 'when' and 'where' are taken at different stages during the protein production process, we study the regulatory mechanism operating at the first stage known as transcription, in which DNA is converted to messenger RNA. Regulation at this level is achieved by a class of proteins called transcription factors, whose activity may be regulated by the environment, either directly or via complex signalling cascades. Transcription factors represent the major focus of our research. We investigate how they regulate gene transcription, the mechanisms by which they themselves are regulated, and the interactions of these factors with other cellular processes, such as metabolism.

Selected publications

Ilsley GR, Fisher J, Apweiler R, De Pace AH, Luscombe NM. Cellular resolution models for even skipped regulation in the entire Drosophila embryo. Elife. 2013 2:e00522.

Zarnack K, König J, Tajnik M, Martincorena I, Eustermann S, Stévant I, Reyes A, Anders S, Luscombe NM, Ule J. Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements. Cell. 2013 152(3):453-66.

Martincorena I, Seshasayee AS, Luscombe NM. Evidence of non-random mutation rates suggests an evolutionary risk management strategy. Nature. 2012;485(7396):95-8

Nicholas Luscombe

nicholas.luscombe@crick.ac.uk
+44 (0)20 379 61132

  • Qualifications and history
  • 2000 PhD from University College London, UK
  • 2004 Postdoctoral Fellow, Yale University, USA
  • 2005 Group Leader, EMBL-European Bioinformatics Institute, Cambridge, UK.
  • 2012 Established lab London Research Institute, Cancer Research UK, Professor of Computational Biology, University College London, UK
  • 2011 Adjunct Faculty, Okinawa Institute of Science & Technology, Japan
  • 2015 Winton Group Leader, the Francis Crick Institute, London, UK