Tackling the spread of disease through a UCL-Singapore connection

PhD candidate Cedric Tan (UCL Genetics Institute) – an A*STAR National Science Scholarship recipient – is using bioinformatics to understand more about how pathogens jump between species.

Cedric Tan completed his Molecular Biology BSc at UCL, before embarking on a year-long research project at the Agency for Science, Technology and Research (A*STAR) – based at the Genome Institute of Singapore (A*STAR GIS). He returned to UCL to undertake his PhD in pathogen genomics, and is making new discoveries about the spread of disease. 

An early love of science

Growing up in Singapore, Cedric Tan has loved science since primary school, where he built and launched PET water bottle rockets, and measured ambient humidity using strands of hair. During high school, he discovered a passion for research too. His first taste of research was a school food science project, where he explored different ways of washing organic vegetables. Although pesticides aren’t used to grow organic vegetables, the sanitation process usually involves chemicals, so Cedric investigated a range of safer and cost effective ways of washing vegetables before they’re sold.

“I really enjoyed that process,” Cedric said. “That’s when I realised I should think about research more seriously as a career.” Keen to study overseas, he found a scholarship opportunity through A*STAR, where he could gain ‘full ticket’ funding to study for both an undergraduate degree and a PhD at UCL. It was his Molecular Biology BSc at UCL that shaped the future direction of Cedric’s research.

“A life-changing moment for me was when I studied a module on computational biology in my second year,” Cedric said. “Before that, I didn't have much computational biology or programming experience. But that module really gave me the fundamental knowledge and skills to do all the work that I'm doing today.” Through that module, a teaching assistant also introduced Cedric to his current PhD supervisor. “That module has really shaped my whole career trajectory so far.”

Researching the blood microbiome in Singapore

During his undergraduate degree, Cedric worked on a project about bloodstream infections, using sequencing data from blood samples to try to predict whether patients have sepsis. Through this project, Cedric realised there wasn’t any data about microbes in the bloodstream of healthy individuals. Due to spend a year at A*STAR as a research assistant following his undergraduate degree, Cedric suggested his idea to research this to his supervisor in Singapore.

“My supervisor was really enthusiastic,” Cedric said. “There’s a national-level sequencing project in Singapore called SG10K. The idea is to collect blood samples from 10,000 individuals in Singapore to sequence and reconstruct their human genomes. Because the sequencing was done in an unbiased way, you can take away all the human DNA, and just look at the microbial DNA in the data to explore the hypothesised blood microbiome. And that's what we did for this project.”

As a result of his undergraduate degree and his experience at A*STAR, Cedric was able to hone his bioinformatic skillset. Interested in genomics – exploring sequencing data and deriving biological insights, Cedric began to focus on pathogens – and how they cause disease, spread, and jump between different host species. This formed the foundation of his PhD topic, which he returned to UCL for.

PhD discoveries

“The Covid-19 pandemic was caused by a coronavirus, which we think jumped from bats into humans,” Cedric said. “It’s host jump events like these that I’m interested in. So the first part of my PhD looked at host jumps across all viruses, trying to identify determinants of host jumps. I was interested in whether there’s a difference between generalist viruses that infect a broad range of hosts, and specialist viruses that can only infect one or two different host species. I wanted to know whether we can identify some phylogenetic or evolutionary determinants of their host range.”

This line of inquiry led Cedric towards a group of amphibian viruses, which can infect most cold-blooded animals. “There are different patterns of genes that have been gained and lost over time in these amphibian-associated viruses, as they learn to infect new host species,” Cedric explained. “Most interestingly, we found that some of these viruses carry collagen genes, which is what we usually associate with higher organisms like mammals. It seems like these viruses may have stolen this gene from the hosts they infect.”

Key findings like this demonstrate how looking at specific viral systems – and identifying evolutionary determinants of host range – can tell us more about the behaviour of pathogens that jump between species. 

Currently working on the final part of his PhD, Cedric is exploring how antimicrobial resistance genes – which cause drug-resistant infections – are passed between different bacteria and spread across host species and environments, such as from waste water into soil, drinking water and then humans. 

“If we can figure out where the major risk areas and transmission routes for antimicrobial resistance are, then we can try to stop the flow,” Cedric said. “For example, if we discovered that pigs have a high level of antimicrobial resistance that spills over into the human population, then we can design strategies to stop that flow. I also want to look at the tools and technologies we can develop to detect the flow of antimicrobial resistance, and the presence of antimicrobial resistance within different niches.”

Due to work for A*STAR for five years following the completion of his PhD, as the final part of his scholarship programme, Cedric hopes to gain a grant to take this area of research forward in Singapore.

Cross-country, multidisciplinary research

Cedric believes his journey through UCL and his experiences with A*STAR have been instrumental in enabling his research career to flourish. “When I return to Singapore, I’ll leverage the connections I have built in both the UK and Singapore to further this area of research,” he said. “We have really achieved cross-country, multidisciplinary research through this work.”

Furthering our understanding of an important topic is not the only outcome of his PhD. “My projects have taught me how to collaborate and communicate well,” Cedric said. “Dealing with people isn’t something you’re taught at school. But explaining to stakeholders and experts from different fields what I do, and understanding what they do, has helped me to develop these skills, which will definitely come in handy in forging future collaborations. You need to be able to find common ground, and to move towards a common goal. That’s one of the main takeaways of my PhD.”

Cedric urges others interested in a research career to spend time understanding what they’re really interested in. “To do that, you just have to go for every opportunity you’re given,” he said. “Many of us are afraid of uncertainty or failure. But even if you have a negative experience, that helps you understand what you don’t like, and refine who you want to become. There are no bad opportunities.”

Further links

• UCL and South Asia
• Cedric Tan’s academic profile
• UCL News: No common blood microbes in healthy humans 
• No evidence for a common blood microbiome, Nature
• No microbial community in the blood of healthy individuals, Nature
• A*STAR National Science scholarship
• A*STAR Research Attachment Programme
• Singapore International Graduate Award

Image

Featured image: Headshot of Cedric Tan

In-article image: Hypothetical network illustrating the flow of pathogens between host species and environments. Image credit: Prof François Balloux, UCL Genetics Institute.