I have fond memories of walking down the corridor towards the Parkhill lab and just thinking “I’m so glad that I’m here, this is amazing.” There was a really good atmosphere at the Sanger during the four years I was studying for my PhD. It was the period during which the microbial genomics field was beginning to move beyond creating reference genomes and we were starting to re-sequence some of the major disease-causing bacteria. This allowed us to generate data at a scale sufficient enough to construct phylogenetic trees and look at how bacteria evolved and adapted over time to better understand transmission and outbreaks. Everyone was doing super exciting stuff and I loved every minute of it.
Curiously, the direction of my PhD, and much of my subsequent career and life can pretty much be traced to a single moment in 2010. I was working with Stephen Bentley when he asked, “So what do you want to work on then: ‘Strep pnuemo’ or TB?” A split second later, having mentally flipped a coin, I was working on Mycobacterium tuberculosis and had begun down the path towards starting a research group focused on the lung microbiome. In addition to using genomics to investigate M. tuberculosis outbreaks, patient-to-patient transmission and long-term evolution, I also collaborated with Andres Floto at the University of Cambridge looking at transmission of Mycobacterium abscessus in patients with cystic fibrosis (CF).
A genomic eye on lung infection
The diversity of bacteria found in the lungs of CF patients is fascinating. Unlike most infections, which are cleared pretty quickly by the immune system or antibiotics, infections in the lungs of CF patients can last for decades, which means that there is loads of opportunity for evolution. Following a stint as a post-doctoral fellow in the lab of Judy Breuer at University College London, I obtained a fellowship to continue my work with Andres Floto at the University of Cambridge to look at the genomic diversity of M. abscessus and other microbes in the lungs of CF patients.
It was generally assumed that M. abscessus present in the environment infected CF patients independently, but using whole genome analysis of a global collection of clinical isolates, I was able to show that the majority of infections were down to a small number of dominant strains that have evolved the ability to circulate globally by human-to-human transfer. This totally changed the way that we need to think about how to treat and prevent infections in patients with lung conditions. Disrupting transmission chains between people for highly infectious strains requires entirely different control measures compared to those needed for preventing infections from environmental sources. It also provided a great example of the power of using genomics to inform clinical practice and public health policy.
Back to the lab
It niggled me for a long time that, other than my time at GSK, I was mainly a bioinformatician, and hadn’t spent much time actually doing experiments in the laboratory. I relied on colleagues and collaborators to generate the data that I analysed. Aware that I wanted to be able to be more self-sufficient, I made sure that during my fellowship I got back to the bench. It’s important to me to be able to understand the entire process from experimental design, through sampling and sequencing, to the analysis and interpretation of the data. That way, if something isn’t working, I am better placed to identify and fix the problem. With that said, if you told me that I could never be in a lab again, I could live with it – these days my main passion is for thinking about the right questions to ask, how best to go about answering them, and then analysing the data generated. I get such a buzz when we have some new data in the lab and we spend ages looking at it and talking about what it means, and how it influences what we should do for the next experiment. It’s those moments that I think I have the best job in the world.
Throughout my career it’s sometimes been hard to shake the feeling that each new opportunity has arisen through sheer luck. I’ve also had to live with some people assuming that having a noted scientist in my family tree has opened doors for me, although if anything the opposite is probably true – tall trees cast long shadows. But when I think about it logically, it’s neither something in my DNA nor just luck. Rather, it’s been a lot of hard work, commitment and team work, both on my part and from my mentors, colleagues and collaborators that have created the right conditions to do great science and create new opportunities. Even during the periods over the last five years when I have been away from the lab on maternity leave, I’ve been able to rely on amazing support from the Floto lab to keep our work on track. It’s something that I am very mindful of as I establish my own group.
Our understanding of how the lung microbiome and host factors affect the evolution of respiratory pathogens over time, and how this influences health and disease, is still at an early stage. But I am incredibly excited to be coming back to Sanger to create a team to tackle this important gap in our knowledge and to use this information to improve treatment for patients with chronic lung conditions.