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.
Long distance transcriptional interaction in rheumatoid arthritis
We have developed methods (Capture HiC) to interrogate the regulatory DNA regions that are associated with rheumatoid arthritis, to determine their interacting gene targets. Expanding on this work by incorporating time-course analysis and measurements of DNA activity (including RNA-Seq, ATAC-Seq), we are now better understanding the functional consequences of genetic risk to disease.
Principal investigator: Dr Stephen Eyre
Biological clocks and epigenetic mechanisms
We investigate how timing mechanisms drive inflammatory immune responses, with a particular focus on how clock-controlled nuclear hormone receptor activity is regulated by polycomb/trithorax mediated chromatin modifications.
We also work on how the clock is coupled to seasonal/circannual timers in the pituitary gland, with a specific interest in how enhancer of zeste 2 (EZH2) regulates long-term dynamic changes in chromatin state to drive neuroendocrine circuits.
A recent project has extended this to studies of hibernation mechanisms in arctic ground squirrels in Alaska.
Principal investigator: Professor Andrew Loudon
Mechanisms underlying scarring in fibrotic diseases
We are interested in understanding how excessive matrix is produced during fibrotic diseases (e.g. affecting liver, kidney and lung) and how cells respond to the altered environment induced by scarring. Our work provides insight into the transcriptional and signalling mechanisms of fibrosis to identify novel targets for anti-fibrotic drug development and/or as diagnostic markers of disease severity and progression.
Principal investigator: Dr Karen Piper Hanley
Other major gene expression and chromatin signalling research activity
Gene regulatory programmes driving cell fate decisions
Signalling and transcriptional dynamics
Chromatin structure and gene regulation
RNA fate and function in gene regulation