Chance encounters with polio throughout her life embedded a fascination of viruses in Rebecca. She is now developing new anti-viral treatments for single strand RNA viruses.

In the future she wants to continue her research with a focus on plant viruses that impact global crop production. She also cares about her ability to communicate her research and its importance to the public.

Rebecca is a Postdoctoral Research Fellow in the School of Molecular and Cellular Biology.

Read more about Rebecca and her research.

Transcript

[Rebecca is sitting in front of a white background speaking directly to camera.]

Rebecca: When I was ten, I was living with my family in South India and my parents were working in the medical college in Vellore. I remember listening to local doctors talking about their efforts during the polio virus eradication. They would run clinics to offer vaccines to local communities, but to reach everyone within these communities, they would head out before dawn and after dusk to make sure that all the workers would be offered the vaccines both before and after their shift. And they would do this seven days a week for months on end just to make sure whole communities would be protected against this disease.

I didn't think much about polio virus after this until as an undergraduate I took a course on virology. And this was taught by a semi-retired professor who would bounce into the lecture theatre every week, profile a virus, tell us about all the strains and show us horrible pictures of disease in humans and other animals. One week the virus family he spoke about were the picornaviruses and this includes polio virus.

Here I learned that polio virus is still not eradicated and that it is a very simple virus. It has just one strand of RNA encapsulated in a simple protein shell. And despite the simplicity, there's still a lot that we don't know about this family of viruses, and we still struggle to combat them.

So, following my undergraduate degree, I decided I wanted to study this further and look into strains of viruses circulating. So, I got a project studying rotavirus in pig and human populations in the UK. Now, I thought this is going to be really exciting. Mapping these strains of viruses circulating in these pig populations and how they crossed over with humans. But the reality of it was that I spent a lot of time scraping piglet diarrhoea from farms. And while the results were interesting, they showed us there wasn't much crossover really between pig and human strains of rotavirus. So, following this time, I decided that I wanted to do was focus on what made these viruses similar compared to the variants that are circulating in the community.

So, I was fortunate to get a PostDoc position here at Leeds studying RNA structure of viruses during assembly. And this focused on picornaviruses, of which polio virus is one. So, the RNA inside these viruses is a single strand of RNA. But it is not just randomly smushed into the capsids. It forms structures and structures that we're interested in are Stem loops. Now, these loops have a STEM with the RNA bound to itself and then a single stranded loop with a specific sequence across this region. And we believe these loops are important for the packaging of viruses inside cells during replication.

So, this is one area that we're really keen to study. But it's really tricky to study this without disrupting this RNA structure. So, the method that we are developing to study the RNA structure inside viruses is called X-ray foot printing. And this uses beamline radiation, which is shot at the viruses in frozen samples to disrupt the RNA structure inside the viruses. And it breaks apart the RNA, but only where its single stranded, not where it's paired with itself, bound to itself, or where it's in contact with the protein shell. And this means after we exposed these viruses to this beamline radiation and it breaks apart in these single stranded regions, we can extract the RNA out and then we can use those breakpoints to build up a 3D jigsaw of the virus RNA structure inside the virions.

And this is fascinating because we can actually go to a single nucleotide resolution of the structure of the RNA, to see where it's bound to, the protein and to itself. What this allows us to study is the sequence and the shape of the RNA during the assembly of viruses and find out what's important.

What we found, using this technique and other techniques, is that these stem loops are really important for picornavirus assembly. And that the sequence of this loop region at the top is conserved, not only between strains of the same virus, but actually between different viruses within this family.

And our overall aim here is that if we can study further this sequence and the conservation of it, we will be able to find small molecule drugs that can bind to this and disrupt it during the assembly of viruses. And this could have a huge impact on disease burden within the picornavirus family.