Scheme: University Research Fellowship
Organisation: University of Oxford
Dates: Oct 2013-Sep 2018
Summary: The overall aim of my research is to use mathematical modelling in conjunction with experiment to investigate novel mechanisms of gene regulation. The central dogma of molecular biology is the flow of information from DNA to RNA to proteins, through the expression of genes by transcription to generate mRNA and the translation of this RNA into protein. Many complex biological processes are controlled at the first of these stages by the regulation of gene expression. By regulating the amount of RNA that is produced, the amount of protein produced can also be regulated and, as proteins are the workhorses in many key cellular processes, this can control a cell.
Current understanding of gene regulation is heavily focussed on transcription factors; proteins that bind near the start of a gene and aid or hinder the firing of the RNA polymerases that read the DNA and copy its information into RNA. However, the emerging picture is one of far greater complexity. Genes can also be regulated by transcription that produces non-coding RNA – RNA that is not used to make proteins – many of which are made in the reverse direction (antisense) to a gene. Furthermore, in many organisms the DNA itself is wrapped around histone proteins that can be modified in various ways which are thought to be a part of regulating expression. The mechanisms by which these elements affect gene regulation and interact with one another are currently poorly understood.
Gene regulation is a fundamental process in biology and a major player in the development of disease; cancer, for example, can be regarded as a disease of aberrant transcription. An increased understanding of the mechanisms underpinning gene regulation will aid other researchers studying any system that involves transcription and could lead to new and improved therapeutics for multiple diseases.