Dr Natalie Ring on the use of nanopore DNA sequencing to predict antibiotic resistance

She completed her PhD in microbial genomics at the University of Bath, where she used nanopore sequencing to study the genome of the bacterium which causes whooping cough. 

Natalie joined Prof. Ross Fitzgerald's research group at the Roslin Institute's Laboratory for Bacterial Evolution and Pathogenesis (LBEP) as a postdoctoral fellow in 2019. Her primary research project involves developing methods for culture-free prediction of antimicrobial resistance in canine infections using nanopore sequencing. Since July this year, she has been appointed as a Senior Research Scientist at the Royal (Dick) School of Veterinary Studies, where she is working to translate her Roslin research findings into practise and develop further diagnostic assays. She also manages the clinical biobank at the R(D)SVS Hospital for Small Animals.

Could you briefly summarise your work?

I am developing and implementing methods to diagnose infections and predict antimicrobial resistance directly from veterinary patient samples using nanopore DNA sequencing. By skipping out the usual culture step during which bacteria from the samples would be grown, we hope to be able to speed up diagnosis by nearly two days (or longer), meaning appropriate antibiotics and/or other treatments can be started much sooner.

Why is your research important? How is it relevant to people's lives?

Rapid diagnostics is a very busy field right now: we live in a world where antimicrobial resistance is rapidly increasing, to the extent that some infections are now resistant even to last line antibiotics, which have traditionally been used to treat infections which don’t respond to anything else. We therefore need to be treating infections more carefully - instead of treating suspected infections with broad-spectrum, “target everything” antibiotics, we want to be making better choices and using the right antibiotic, at the right time, for the right infection. The tests that I’m developing for vets to use are equally applicable to humans; in the future, your own infection might be diagnosed by DNA sequencing!

What are the major challenges in your field?

Keeping track of what everyone else is working on! So many people are working on similar things (which is great, because it’s such an important field), it’s easy to get left behind or miss out on an important development if you aren’t paying attention.

We may also come up against some barriers as we try to deploy our rapid diagnostic methods, because although they will be faster and allow us to choose the most appropriate treatments, in many cases they are also likely to be slightly more expensive. Pet owners may prefer to go for the slower, cheaper option and just start using a potentially less suitable treatment or broad-spectrum antibiotic in the meantime. We will need to work hard to convince them that the benefits of our methods outweigh the costs, in the interests of preserving antibiotics for the future.

What inspired you to be a scientist?

I have always just wanted to understand everything and know everything there is to be known, in all areas of life, which is obviously a totally realistic goal. At school, this meant I was passionate about the sciences, and English Literature (you can learn a lot from reading books, even if they are fiction!). The more I learnt about genetics, the more it seemed to me that DNA holds the answers to many of the Big Questions in biology and nature - in my opinion, what is written in our genomes is the basis to everything there is to know (albeit with lots of other important stuff layered on top). I am also a bit of a hypochondriac, so have more than a passing interest in diseases of all sorts. The work I’m doing now is great, because I get to combine my love of genomes with my somewhat morbid interest in diseases.

What do you like best about your job? What do you like the least?

I love the flexibility of being a researcher. What I’m working on from one day to the next might change completely, depending on who’s asked me for help, or what has taken my interest overnight. On the other hand, I also enjoy the satisfaction I get from taking a big project from start to finish, and really focussing deeply on just one thing. Seeing my name on a published paper, or on the agenda for a big international conference never gets old!

What I like least is probably the temporary nature of many research contracts, and the need to move from place to place to be where the most relevant job is to you. Although I love Edinburgh (and before this, Bath, and before that, Oxfordshire), part of me would have really loved just staying closer to home and setting up a life and career nearer to my family and friends back in Essex.

If you could have tea with another scientist (alive or dead), who would it be? What would you talk about?

At risk of getting sentimental, I’d have tea with the group of people I did my PhD with. We all left Bath towards the end of 2019 and scattered all over the UK (and rest of the world), never thinking it would be nearly 3 years later and we wouldn’t have been able to go back to Bath for graduation yet! We’d talk about what we’ve been doing with our lives since we finished our PhDs and left Bath.

A more traditional response would be that I’d have tea with Frederick Sanger, who is basically the Godfather of modern DNA sequencing. We’d talk about how much sequencing has progressed since he developed his sequencing method, and where he thinks the technology might go next.

What is the most unusual thing you have done as a scientist?

I recited a poem I’d written about Bordetella pertussis on stage in front of several hundred people at a conference in San Francisco! This is a long(ish) story…

In 2018, I applied to a new competition Oxford Nanopore Technologies was running for early career researchers, called “The Spotlight Session”. To enter the competition, you wrote a traditional conference abstract for a presentation about how sequencing was changing your field of research, but also made a video application explaining why you should be chosen to attend their meeting in San Francisco. The winners would be flown over, all expenses paid, and at the meeting, each ECR would get 2 minutes to convince the audience that they should be chosen to do their research presentation. After the pitches, the audience would vote for their favourite, who’d present then and there on the main stage.  

For my video, I wrote a poem about my PhD research into Bordetella pertussis (the bacterium which causes whooping cough), and then filmed myself reading it in front of the very scenic lake and water feature at the University of Bath. When I wrote my poem, a couple of friends were desperate to read it, but I was too embarrassed. We made a bet that if I won the competition and made it to San Francisco, not only would I let them read the poem, but I would also use it for my 2 minute pitch to the audience. As you’ve probably guessed by now, I did win the competition, and a few weeks later there I was on the stage doing my poetic pitch. Unfortunately for me, one of my fellow winners was a medic who was doing research which was much more interesting to a general audience, so I didn’t win the audience vote and get to present on the main stage, although it was a close call. I did do my presentation in one of the break-out rooms though. And it was definitely worth it for the free trip to San Francisco and getting to attend the meeting. I’m still friends with some of my fellow Spotlight Speakers!

(BTW, Nanopore still run this competition for their annual London Calling conference in the summer and Community Meeting, usually in New York, in the winter. I’d recommend anyone who’s using nanopore in their research applies, it really was a great experience!)

If you weren’t a scientist, what would you be doing?

Remember when I said I loved English Literature? Probably that. I still have a not-very-secret dream of writing a novel one day. In 2019 I did the next best thing though, and wrote a chapter for a book about the science of Doctor Who, imaginatively titled “Doctor Who and Science”. My chapter was about the potential genetics of Time Lord regeneration.

Do you have any advice for people who want to go into this field of research or start a career as a scientist?

You don't have to know exactly what you want to do in the future when you're first getting started. When I applied to do biochemistry for my BSc, I had no idea what I’d end up doing. Even after I finished, I worked for 4 years before seeing a genomics PhD project I wanted to go back for. To be honest, I still don’t really know what I’ll be doing in 10 years. I’m just doing projects I think are interesting and having fun along the way. There isn't just one track for everyone, and there is a path for anyone :)

What do you think are the major challenges facing humanity? How can science help?

The obvious answer here for me is antimicrobial resistance, which is a disaster waiting to happen. It’s another lengthy one. For a TL:DR, just visit the link in my last sentence…

Before antibiotics, life was much more risky. Seemingly minor surgeries or wounds could be life-threatening, because if you got a bacterial infection, we didn’t have a good way of treating it. Starting with the discovery of penicillin in the 1920s, there was a bit of an antibiotic “gold rush” over the next several decades, with a load more being discovered and developed.  Some bacterial infections which could previously have been very serious (think things like UTIs, chest infections) now seem more like easily treated everyday ailments, and bacterial complications from medical procedures (including childbirth) are, thankfully, very rare. Even some more serious or deadly diseases, like tuberculosis, are relatively easily treated with antibiotics.

But now we have a problem. Decades of antibiotic use (and overuse) have resulted in an increasing number of bacteria becoming resistant to our gold-standard antibiotics. Like us, bacteria are constantly evolving and adapting, so it was always inevitable that resistant strains would emerge. But we have overused antibiotics to the extent that this resistance has developed much faster than we would have hoped. And we haven’t really discovered any new antibiotics in the last several decades.

It's not all doom and gloom though. Scientists all over the world are working hard to develop new ways of treating bacterial infections, without the traditional antibiotics. One very cool new area being explored is bacteriophages, viruses which infect bacteria. And new(ish) technologies like DNA sequencing are allowing us to monitor the bacteria out there in the wild, to keep track of how antimicrobial resistance is growing.

We have the tools to tackle the issue of antimicrobial resistance, we just need people around the world to be mindful and cautious about their use of antibiotics now, to give us time to deploy those tools. Sign up to be an “antibiotic guardian” to help give us time.

Related Links

Natalie Ring profile

Fitzgerald Group