Staff profile

Having graduated with a BSc in Biosicences in 2024, I began my Biochemistry PhD in the October of the same year. My PhD focuses on the molecular basis of RNA recognition by TRIM56's RNA-binding domain.

TRIM56 is a crucial protein in the human innate immune response. TRIM56 acts as an E3 Ubiquitin ligase, meaning it is able to catalyse the transfer ubiquitin groups to substrates. This ubiquitination activity is important for upregulating signalling pathways involved in pathogen recognition. It also enables TRIM56 to label pathogen proteins for destruction to protect human cells. TRIM56 conveys specificity to this reaction by tethering specific proteins with its C-terminal 'NHL' domain. This NHL domain has an unknown structure but AlphaFold predictions suggest it forms a highly complex 'beta propellor' fold. 

Unusually, TRIM56's NHL domain able to bind directly to viral RNA as well as proteins. The formation of TRIM56-NHL-RNA complexes leads to downstream inhibition of viral replication. This allows TRIM56 to inhibit the replication of Dengue virus, Zika virus and HIV-1. This RNA-binding activity is poorly understood. It is not known what RNA sequence or structural motifs are bound by TRIM56's NHL domain, or whereabouts these motifs feature within viral genomes.

In my PhD project, I am using a range of structural and biophysical techniques to study the TRIM56-NHL domain. I am expressing and purifying the TRIM56-NHL domain in Escherichia Coli.  I aim to structurally characterise the NHL domain using a combination of methods, including BioSAXS and X-ray Crystallography. I want to use RNA-binding assays to decipher TRIM56-sensitive RNA motifs. In parallel, I hope to study the affinity of viral genomes for this protein, revealing the virologically-relevant action of this enigmatic defensive protein.