Drug screening

Chronic inflammatory diseases such as COPD and arthritis are often characterised by unresolved neutrophilic inflammation. Currently available anti-inflammatory therapeutics are largely unsuccessful and there is a demand for novel, more effective therapies.

To approach this challenge, we designed a partially automated chemical screening assay using transgenic mpx:GFP zebrafish larvae to identify compounds that can drive inflammation resolution. We perform tail fin transection on larvae at 3 days post fertilisation to induce an inflammatory response. Four hours later, once neutrophils have been recruited to the wound, we array the larvae into 96-well plates containing the screening compounds.

These plates are imaged on an automated fluorescent plate reader at 12 hours post injury, when we can detect compounds that have accelerated inflammation resolution by reducing neutrophil numbers at the wound compared to the control larvae. Using this approach, we have identified a number of new pro-resolution compounds, some of which may be of potential therapeutic benefit and help us to unravel the molecular mechanisms that regulate inflammation resolution.