An interview with Ashley Otter

Ashley Otter is a research scientist within Diagnostic Support for the rare/imported pathogens laboratory (RIPL) at Public Health England (PHE) Porton. Here he tells us why he decided to pursue a career in microbiology, gives us an insight into his PhD research which involved working on a transcriptional regulator that is missing from the genome of all Mycobacterium bovis isolates (and a lesser known Mycobacterium caprae, which is closely related to M. bovis) but highly conserved in all other species of Mycobacteria, including Mycobacterium. tuberculosis. He also found time to give a little advice to anyone thinking about a career change and why be joined the Microbiology Society.

© Ashley Otter

Tell us a little about your current role in the rare/imported pathogens laboratory with PHE.

I currently work as a research scientist within Diagnostic Support (DSP) for the rare/imported pathogens laboratory at Public Health England (PHE), Porton, UK. It involves testing, validating and researching diagnostic tests (PCRs + serology) for rare/imported pathogens such as filoviruses, chikungunya, anthrax, Coxiella etc. As outbreaks of new pathogens often appear rapidly and without warning – such as the Ebola and Zika outbreaks – new diagnostic tests need to be created, tested, validated and then rolled out for diagnostic use by the frontline biomedical scientists to use. This is in addition to many pathogens routinely changing or evolving, and so our diagnostic tests need to be constantly tested and improved to reflect these changing pathogens.

How easy was it making the switch from research to industry?

I would say fairly easy. I still get to do research and also have the flexibility like academia, and I really like working on research that has a direct, real-world benefit, particularly in diagnosing rare infections. I think the team that I get to work in is really exciting, as we get to research, develop and validate new diagnostic tests for rare pathogens and then see our work implemented in PHE in helping to diagnose patient infections and aid in providing them with the relevant treatments. Plus, the pension scheme and flexible working are a great bonus.

What advice would you give to anyone who is thinking about a career change?

Just give it a try! If you like the sound of a job – go for it. Even if you don’t think you’re a good fit, it’s always worth speaking to the person recruiting the job (i.e. lab supervisor, project manager etc), as some jobs can be advertised as highly generic but actually be highly specific. But even if you try a career change and don’t like it, you can easily learn new skills or expand on what you already know to then benefit you for your next position. I always thought career paths were well defined but working with diverse people throughout my PhD and in industry, you realise not everyone does the ‘BSc > MSc > PhD > post-doc > lecturer’ path and that’s fine!

What encouraged you to pursue a career in the field of microbiology?

I think I was always fascinated by how people got ill, particularly after learning about the black death at school. But when I first started my A-levels, I was able to study just a small bit of microbiology – comparing eukaryotic and prokaryotic cells. I also had great A-level teachers that helped me further explore my interest and aided in me obtaining work experience in a hospital microbiology lab. I got enthralled by all the diverse bacteria, fungi and viruses out there, so I decided to study for a BSc degree at Cardiff University, where I had some great lecturers (all of which shared my microbial passion!) and did 12 months in a lab working on bacteriophages of anthrax. After this, I simply couldn’t not continue with microbiology, so after I graduated I began a PhD on transcriptional regulators of tuberculosis at the Royal Veterinary College, UK. After finishing my PhD, I did a brief stint at a small biotech start-up called Microgenetics, where I worked on a rapid diagnostic for bovine tuberculosis and now I’m a research scientist at PHE.

That moves us on nicely to your PhD research – tell us a bit about it.

My PhD was working on a transcriptional regulator that is missing from the genome of all M. bovis isolates (and a lesser known M. caprae, which is closely related to M. bovis) but highly conserved in all other species of Mycobacteria, including M. tuberculosis. We found that the regulator is highly conserved across 5,000+ strains of M. tuberculosis, with only a handful of independent SNPs occurring throughout the gene, and with only 1 SNP occurring in its regulatory motif out of 5,000 strains! We set out to determine the role of this regulator, so we purified the protein for DNA binding assays and created knock-out mutants in both M. tuberculosis and a less virulent model - M. marinum (a close relative of M. tuberculosis that you can work with at lower containment level). We did lots of studies on these mutants, looking at quantitative PCR (qPCR) of surrounding genes, cell infections, antibiotic resistance testing and lots of growth curves. Hopefully the paper will be out soon.

M. tuberculosis is such a challenging pathogen to work with – tell us about M. bovis and how it differs.

Yes, working with M. tuberculosis is really difficult, both the high containment and the extremely slow growth rates. M. bovis is pretty much the same, slow growth rates and similar high containment, but also having to deal with it being a pathogen listed on the Specified Animal Pathogens Order (SAPO) list – as it is a specialised animal pathogen. One difficulty is that many of the molecular tools available for tuberculosis (TB) research are not always applicable to M. bovis and require a bit more troubleshooting and changing. This is mostly because the common M. tuberculosis strain; H37Rv, is more suited for laboratory growth (but still also cause TB) whereas for M bovis, it isn’t quite as adapted to growing on agar plates and more adapted to growing in the lungs of cows!

Antimicrobial resistance in TB has been identified by the World Health Organization as a public health crisis. How does the pathogen develop resistance and how are new treatment options being developed?
M. tuberculosis isn’t quite like other bacterial pathogens in that it doesn’t undergo horizontal gene transfer, so all of the resistance mechanisms in M. tuberculosis are through intrinsic resistance mechanisms or chromosomal mutations. There is a great article out in the European Respiratory Journal (ERJ) which discusses many of the SNPs or indel markers associated with increased resistance to antibiotics in M. tuberculosis (Eur Respir J 2017; 50: 1701354) and lots of great work is being conducted by the CRyPTIC consortium on the 100,000 M. tuberculosis genome project, which is looking to further understand antibiotic resistant M. tuberculosis.

And finally, why did you join the Microbiology Society?

The Microbiology Society is great –  I joined as they offer support for early career researchers to attend conferences (like the Microbiology Society Annual Conference and the Early Career Microbiologists’ Forum Summer Conference), where you have the opportunity to learn and meet lots of other like-minded microbiologists, and can access various avenues to publish your work. The Microbiology Society particularly helped me during my first year of my PhD, as I was given funds to attend my first Microbiology Society Annual Conference up in Liverpool. Since then, I have attended numerous events run by the Society and they have been really helpful for networking and learning about new microbiology techniques and discoveries.

Are you a member and interested in sharing stories about your research journey? Email [email protected]