Lay summary
High levels of uric acid cause gout. Uric acid is made in the blood and levels are regulated by urinary excretion. Drugs that lower uric acid can prevent gout. Genetic studies have identified approximately 30 reasonably precise, but not exact, areas of the human 'genome' (DNA) that control levels of uric acid. We think that most of these regions control the amount of protein made rather than how the proteins work. However this has not been confirmed, if we could do this we would transform approaches to drug discovery. We will use an innovative zebrafish readout system that can tell us which exact points in the human genome control the amount of a particular protein made that controls urate levels. The major transformative aspect is to alter the paradigm for drug discovery to include drugs that would regulate amounts of protein made, rather than how proteins work.