Having completed tertiary education across Southeast Asia and India, I pursued research towards a doctoral degree in Molecular Neurobiology at the Institute of Neurology, University of London. I then completed post-doctoral research stints at the National Institute of Medical Research, Mill Hill, and at Oxford University prior to setting up the Nuclear Signalling Laboratory at the Randall Institute, King’s College London in 1990. In 1999, I moved with my laboratory to the Department of Biochemistry at Oxford and I joined Trinity College as the Fellow in Biochemistry.
I provide lectures and tutorials in basic cellular and molecular biology, as well as in more advanced topics such as cancer biology, intracellular signalling mechanisms, chromatin biology, epigenetics and gene regulation. A stimulating part of my engagement with undergraduates at Trinity is to mentor independent vacation research, which involves identifying host laboratories in the UK and abroad, securing the offer of a place and applying for funding to cover travel and subsistence costs.
In the Nuclear Signalling Laboratory, we study the process by which extracellular stimuli rapidly activate a small subset of genes called Immediate-Early (IE) genes in the nucleus. These genes are linked directly by signal transduction circuitry to cell surface and intracellular receptors. The process is highly conserved in evolution and is widely deployed within the organism, controlling diverse phenomena such as cell division, differentiation as well as immunological and inflammatory responses. Our research encompasses three overlapping areas of cell biology: intracellular signalling circuitry, regulation of gene transcription and chromatin biology. Present research centres on (i) understanding the signalling systems and nucleosomal modifications controlling IE genes, especially quantitative influences observed, (ii) on determining causality and identifying the enzymes involved in dynamic histone modifications, (iii) on addressing evolutionary conservation of these processes using other model systems such as Drosophila and Dictyostelium, and (iv) on developing chromatinised transfection-based model systems in which the complexity of these processes is preserved. As these processes regulate the control of proto-oncogenes and genes encoding pro-inflammatory cytokines such as TNFa, there is considerable current interest in deriving inhibitors in the context of cancer and inflammation.
- Live-cell studies of p300/CBP histone acetyltransferase activity and inhibition. Chembiochem. (2012), 14, 2113-2121.
- Dynamic acetylation of lysine-4-trimethylated histone H3 and H3 variant biology in a simple multicellular eukaryote. Nucleic Acids Res. (2012), 40, 7247-7256.
- Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP. Proc Natl Acad Sci USA (2011), 108, 7814-7819.
- Stability of histone modifications across mammalian genomes: implications for ‘epigenetic’ marking. J Cell Biochem. (2009), 108, 22-34.
- Enhanced histone acetylation and transcription: a dynamic perspective. Mol Cell. (2006), 23, 289-296.