Unlocking development, disease and evolution
Changes in gene expression underlie development, disease and evolution. We aim to understand the mechanisms that instruct these changes and how they impact on human developmental disorders and diseases such as cancer, fibrosis and arthritis.
Gene expression is a complex and dynamic process, controlled by a variety of signals across space and time, giving rise to intricate and changing expression patterns.
The overall aim of our research in this area is to understand the molecular basis to these events and their significance in the context of organismal homeostasis, development and disease. We are studying how gene transcription is initiated and terminated and how post-transcriptional mechanisms impact on this.
A combination of gene-centric and genome-wide approaches are used and, in the latter, the importance of long range genomic interactions and 3D folding of the chromatin are a major theme in our research.
A variety of model organisms, including yeast, Dictostelium, frogs, zebrafish and mice, are used alongside research directly in human cells and tissue.
Major research activities
Deregulation of gene expression in disease
Changes in gene expression modify cell behaviour and impair the normal functioning of tissues and organs. In the disease state, abnormal patterns of gene expression result from cells responding to altered environments, changes in long-range chromatin interactions in the nucleus and changes in the timing of cells behaviours.
Gene regulatory programmes driving cell fate decisions
Most cells within an organism contain identical copies of the genome, but selectively use different portion of their genomes and transcribe different genes. We study the mechanisms underlying changes in gene expression and how they generate the myriad of different cell types and produce organ-specific transcriptional signatures in the human embryo.
Signalling and transcriptional dynamics
The dynamic nature of transcription plays an important role in regulating physiological processes, particularly in differentiation and development. We explore dynamic processes at different scales in biological systems, how cells respond to diverse signals and to stress to regulate gene expression, and how changes in gene expression dynamics underlie cell state transitions.
Chromatin structure and gene regulation
The organisation of chromatin within the nucleus profoundly influences gene expression. We study how the actively transcribed genome is organised in the nucleus, how different chromatin components contribute to gene regulation and how variations in these components result in disease.
RNA fate and function in gene regulation
In addition to functioning as a messenger between DNA and protein, RNA is involved in regulating chromatin architecture, gene expression and transcriptional dynamics. We investigate the function of non-coding RNAs in transcriptional and translation control, and how their evolution has contributed to the diversification of animal morphology.
PLoS Genetics (2016) / Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo
Nature Communications (2016) / PAK proteins and YAP-1 signalling downstream of integrin beta-1 in myofibroblasts promote liver fibrosis
Elife (2016) / Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation
PLoS Comput Biol (2017) / Identifying stochastic oscillations in single-cell live imaging time series using Gaussian processes
Dr Stephen Eyre PhD
Senior Research Fellow
Stephen Eyre’s research has been fundamental to our current understanding of the genetics of rheumatoid arthritis. Most recently his work has demonstrated how regulatory genetic elements implicated in disease susceptibility can act over long distances, implicating likely causal genes and biological pathways that drive rheumatoid arthritis.
Dr Gino Poulin PhD
Gino Poulin’s research seeks to understand how signalling events impact on the epigenome to regulate ageing, stress responses, and transgenerational inheritance. His latest work, in collaboration with Alan Whitmarsh’s lab, revealed that the mitochondria signals to the nucleus to alleviate oxidative stress via the respiratory enzyme CLK–1.