From method to discovery and therapy

How viruses take hold
Viral genomes encode control instructions in their structure, not just their sequence. We study how these regulatory RNA elements recruit host and viral proteins to switch transcription and translation on and off — and how that control can be subverted for therapy.
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We work across retroviruses, the arenaviruses, and flaviviruses from the 5'-UTR that drives translation of HIV proteins to the intergenic regions that attenuate Lassa virus and how the 3' UTR of dengue virus gives it the ability to cause infection in the brain. 

When RNA misfolds
Misfolded RNA is the pathological cause of a whole class of neurological disorders — myotonic dystrophy, fragile X, Huntington’s, ALS/FTD.  We investigate how misfolded RNA damages cellular health, with a particular focus on rare diseases such as myotonic dystrophy. We determine the structure and interactions of these RNAs in situ, combining cell biology, microscopy and structural biology, because understanding what the RNA does in the cell is what makes RNA-based therapy possible. 

Building the tools we need
RNA and its protein complexes are among the hardest systems to study using structural biology techniques. So we build the methods we need: we pioneered OrbiSIMS-guided structural modelling of native RNAs, developed affinity-based approaches to cryo-EM sample preparation, and run NMR-restrained simulations of RNA. Integrating mass spectrometry, cryo-EM and molecular simulation lets us reach structures and dynamics that no single technique can resolve — and correlative cryo-EM/cryo-MSI workflows take that into the cell, linking molecular structure to its native context.