Liam Maddison

Probing the function of RNA methylation through chemical biology (iCASE)

About me

I am working towards my PhD at the University of Leeds, under supervision from Professors Richard Bayliss, Adam Nelson and Adrian Whitehouse. My background is in Medicinal Chemistry, which I studied at Leeds University, graduating in 2018 with a MChem degree.

My project

My project, in collaboration with LifeArc, focusses on taking a fragment-based drug discovery approach to develop novel inhibitors of the RNA N6-Methyladenosine (m6A) methyltransferase complex. The dynamic m6A methyl modification constitutes a major epitranscriptomic regulatory mechanism, where RNA-binding proteins can selectively recognise and bind to m6A, affecting the fate of the transcript. This regulatory mechanism has been linked to important cellular processes, including spermatogenesis and circadian rhythm, but my interests lie in what happens upon dysregulation of m6A methylation. Abnormal m6A levels have been implicated in a wide range of both cancers and viruses, presenting the m6A methyltransferase complex as an interesting target for the development of novel therapeutics.

The first year of my project has focussed on studying the catalytic core of the complex, the METTL3/14 heterodimer, using crystallographic methods. Most recently, this has led to the identification of fragment binders across numerous sites, the most promising of which will be developed synthetically to improve their inhibitory properties.