Research
From the moment influenza A virus enters a cell, its RNA is bound, modified, moved and read by host proteins. We want to know which of those partnerships the virus cannot live without.
01 · Fundamental molecular virology
Influenza A virus has a genome of eight RNA segments. Every one of them has to be copied in the nucleus, exported, translated and delivered to the cell surface before a new virus can bud. Each of those steps needs the host.
Highlighted steps are where most of our work sits.
Chemical marks on viral RNA, such as m6A, can change how stable it is, how well it is translated and whether the immune system notices it. David’s earlier work showed these marks enhance influenza gene expression. The same chemistry matters for mRNA medicines, where modified bases such as pseudouridine help an mRNA be translated without triggering an immune alarm.
Influenza replicates in the nucleus, an unusual choice for an RNA virus. Its unspliced RNAs need host help to get out to the cytoplasm, where the translation machinery waits.
New genome segments travel to the cell membrane in vesicles before they are bundled into new virus particles. We have identified host proteins that ride along on that journey.
Under the microscope
02 · Translation to advanced RNA therapeutics
Influenza changes quickly, which is why vaccines are updated every year and antiviral resistance keeps appearing. The host proteins the virus depends on change far more slowly.
If an interaction between a host protein and viral RNA turns out to be essential to all influenza A viruses, it becomes a strong candidate for a new kind of antiviral. RNA medicines, from siRNAs to antisense oligonucleotides, are well suited to hitting those targets.
David has worked on RNA therapeutics from the start: his PhD developed allele-specific siRNAs and CRISPR approaches for inherited eye disease. We are bringing that experience back to infectious disease.
03 · Equitable access
The burden of respiratory viruses falls hardest on communities with the least access to new treatments and vaccines. A breakthrough that only reaches wealthy health systems is only half a breakthrough.
We want the therapeutics that grow out of our work to be designed with affordability, stability and manufacturing in mind from the start, and we look for partners who share that aim.
How we work
Our core programme is funded by a European Research Council Starting Grant. We also study other RNA viruses, including RSV and SARS-CoV-2, with collaborators.
