Professor Samuel Sheppard will start working at the Ineos Oxford Institute (IOI) for Antimicrobial Research in September 2022. Here, we welcome Sam to the IOI and talk to him to learn more about his research and why he is excited to join the institute in helping to address the growing global health problem of antimicrobial resistance (AMR).
In September 2022, Professor Samuel Sheppard will return to Oxford – where he previously worked as a postdoctoral researcher and Wellcome Trust Fellow – as a Professor of Microbial Genomics and Evolution and also as a Tutorial Fellow of St Anne’s College. Sam works at the intersection of microbial epidemiology, ecology and evolution, and will join the new Department of Biology and the IOI with the aim of using fundamental evolutionary and ecological theory to address consequential questions in pathogen emergence and spread.
We interviewed Sam to hear about his research interests, how he feels about coming back to Oxford and what he likes to do when he is away from the lab.
Hi Sam, welcome back to Oxford. We’re very excited that you’ll soon be joining the IOI. For those who don’t know you yet, can I ask that you start by telling us a bit about who you are and what you do?
Sam: I’m a Professor in Microbiology and Director of Bioinformatics at The Milner Centre for Evolution, part of the Department of Biology & Biochemistry at the University of Bath. I run a multidisciplinary lab that combines the use of genomics, bioinformatics and wet-lab experiments to study complex questions related to the ecology, epidemiology and evolution of microbes. Our main goal is to try to understand how and why certain bacteria become pathogenic, and we study various species including Campylobacter jejuni, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Helicobacter pylori. In quite simple terms, we combine the large-scale analysis of genomes from bacterial isolates – which we take from people, animals, food, etc – and compare them to identify genetic differences that may be related to the ability of these bacteria to infect a host, like for example the acquisition of a new gene. Then, we complement this computer-based work with experiments in the lab to try to link those differences to specific characteristics that enable the bacteria to cause infections, for example by showing that the acquisition of that gene helps the bacteria to attach to the host, or to make biofilms, or leads to antimicrobial resistance.
Why are you currently working on these questions? What is your main motivation?
Why are you currently working on these questions? What is your main motivation?
Sam: Most pathogenic microbes are principally commensals that live with us and don’t cause any harm, yet at some point evolve into organisms that cause infections. So, I’m really fascinated about why this happens and with trying to understand how these transitions occur. For example, what are the changes that enable Campylobacter or E. coli to jump from animals to humans? Why is it that staphylococci, which are normally innocuous and present in the skin of all people, sometimes lead to surgical infections? What are the events that lead to H. pylori, which is a common component of the human stomach microbiota, to evolve into strains that are associated with increased risk of gastric cancer? I feel that understanding these questions is not only very interesting because it provides insights into the basic biology of these microbes and how they evolve and cause disease, but also because it can provide relevant information to guide treatments of veterinary and human infections.
We will only be able to deal with AMR if we fully understand how it evolves.
What's your favourite part of the job?
Sam: I have always enjoyed addressing challenging research questions and I get a real sense of achievement when my methods or findings help to move the field forward. However, as I have got older, the most rewarding part of my job increasingly tends to be when I am able to help junior colleagues. I am very proud to see former students and postdocs go on to become independent researchers in their own right.
You worked in Oxford before going to Swansea University Medical School and then to the University of Bath. How do you feel about coming back in September? And why this move to the IOI at this stage of your career?
Sam: Yes, I was a postdoctoral researcher and Wellcome Trust Fellow in the Department of Zoology, which is now merging into the Department of Biology. This is the same department that hosts the IOI, so it feels a little like coming back home. I always loved Oxford, for many reasons including it being such a productive place for research. And the IOI feels particularly appealing to me because it is trying to address such an important health problem, which is AMR. Topically, it’s also a nice fit for my interests. Just like the other examples I mentioned above, the emergence of drug resistance is another case in which microbes evolve in a way that enables them to be more successful at causing infections, so this is something that we’ve worked on previously and look forward to explore much more at the IOI. In fact, and you can quote me on this, I believe that we will only be able to deal with AMR if we fully understand how it evolves – and so this seems like the perfect place to do this. I also really like that the institute is trying to combine diverse expertise in one place, and feel like I can add to that by bringing a bit of a different perspective that is more focused on ecology and evolution. I think this will create easy synergies with a lot of the work currently being done there, including Chris Schofield’s studies on the mode of action of antibiotics, and Tim Walsh’s work on AMR burden across health and agricultural settings. And my focus on bioinformatics, basic biology, and ecology and evolution should be a nice complement to their existing skills with chemistry, epidemiology and medicine.
You work on many different topics from ecology to evolution, with a variety of bacteria and explore different techniques that include wet-lab research to bioinformatics and machine-learning. But if you had to pick one of your career achievements to date,
Sam: Maybe it’s because I’m reminiscing about my previous time in Oxford, but I remember a really nice paper we published in 2013 in PNAS with Xavier Didelot, Martin Maiden, Daniel Falush and other colleagues, which was the first formal genome-wide association study (GWAS) performed in bacteria. I remember sitting behind the Dunn School – where the IOI is currently located! – with Xavier and Daniel overlooking the University Parks and discussing why GWAS, which were already quite common in humans at the time, were so tricky to do in bacteria due to their complex population structure. And so we devised a quite clever method based on aligning short genomic sequences (k-mers) and that took into account the population structure of bacteria, and all of the sudden the data started to make sense and we were able to identify genetic features in Campylobacter linked to the ability of the bacteria to infect different hosts. This method has been widely used and further improved upon since then, but it’s definitely something I’m quite proud of.
[Sam's] arrival at Oxford, with other bioinformatic experts across the University, places Oxford as a leading bacterial genomic center, not just in the UK, but also Europe.
Going back to AMR, and on a hypothetical scenario: if you could snap a finger and change just one thing in the AMR space, what would that be?
Going back to AMR, and on a hypothetical scenario: if you could snap a finger and change just one thing in the AMR space, what would that be?
Sam: The problem with AMR is that it is born of evolution. To stop one you would need to stop the other, and without the force for change life is condemned to a moribund future. So, perhaps a prosaic but realistic answer to this question is the way for me to go. Microbiology is clearly at a turning point in its 120-year history. Widespread next-generation sequencing has revealed genetic complexity among natural bacterial populations that could hardly have been imagined by pioneers such as Pasteur, Escherich and Koch. Exploiting this data cascade has huge potential to tackle the problem of AMR but requires a new way of thinking. So if I could change one thing in research, I would remove traditional barriers between disciplines and bring scientists together to create an integrated future where we all work together towards next generation microbiology.
Interview by Claudio Nunes-Alves, claudio@germinatescience.com