Image credit: Jake Bonham/Jet Photographic

Categories: Sanger Science31 October 2024

Unpicking the puzzle of plasmids – how bacteria share drug resistance

By Carmen Denman Hume, Communications Officer at the Wellcome Sanger Institute

Arnav Lal is interested in merging clinical practice with infectious disease research. He has recently completed his year-long Master’s in Biological Science through the Churchill Scholarship, provided by the University of Cambridge. For his Master’s he conducted research at the Wellcome Sanger Institute on antimicrobial resistance and used genomics to study how bacteria pass mobile genetic elements around. We caught up with him to talk about his experiences before he moved on to his next step, beginning his studies at Harvard Medical School.

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What brought you to the Sanger Institute?

During my undergrad at the University of Pennsylvania I conducted research in the lab of Dr Paul Planet. My research in the lab involved the bacterium Staphylococcus aureus (S. aureus), exploring how S. aureus interacts with the human immune system. This led me to study genes that modify the surface of S. aureus and are involved in human immune responses. While I initially only used molecular laboratory approaches, I supplemented this with computational biology and genomics. The computational work helped us discover insights into the S. aureus surface-modifying genes and led me to develop new computational tools and methods to address our follow-up questions.

I wanted to be a part of the environment that is creating and studying large-scale datasets, building algorithms, and maintaining large pipelines

Throughout all of this work, I used open-access bioinformatics tools that were created, developed, or maintained by the Sanger Institute. I wanted to physically be a part of the environment that is creating and studying large-scale datasets, building algorithms, and maintaining large pipelines.

In order to fund a one-year Master’s degree at the Sanger Institute I was fortunate to receive the Churchill Scholarship through the University of Cambridge. I enjoyed getting to experience living in Churchill College and participated in sports and activities across the city.

What did you work on while you were at the Sanger Institute?

At the Sanger Institute, my research focused on a genetic material called plasmids, which are circular DNA found in bacteria. Plasmids can easily gain or lose genetic material. Some plasmids can even ‘jump’ between different bacterial organisms. A lot of important genes such as antimicrobial resistance genes are often found on plasmids. Plasmids are constantly changing so they are really hard to study. While we can classify bacteria, even sorting plasmid sequences into ‘types’ is a difficult task.

Plasmids are constantly changing so they are really hard to study... For my project, I wanted to find a way to organise all this plasmid chaos.

For my project, I wanted to find a way to organise all this plasmid chaos. We wanted to develop genetic rules and frameworks to follow how everything is changing within regions and ultimately ask ‘Can we predict which plasmids may gain certain antimicrobial resistance genes?’ If we can understand the rules and patterns in these highly-changeable elements we might better predict how bacteria evolve. This could be helpful in understanding the landscape of how plasmids influence disease.

I built the frameworks to understand the rules that govern the evolution of plasmids.  We did not focus on a single type of bacteria, but all the plasmids in bacteria. This analysis took some creativity in developing new unconventional computational approaches. Although difficult, the work has been really rewarding!

To do this research, I worked in the group led by Nick Thomson who is both a group leader and Head of the Parasites and Microbes Programme at the Sanger Institute. Nick, together with senior scientist Adrián Cazares, were my advisors for this project. Adrián is a microbiologist and geneticist interested in the evolution of mobile genetic elements and phages, and he curated a large dataset that I worked with for my Master’s project.

What comes next on your journey?

I have begun my studies at Harvard Medical School in Boston, Massachusetts. My studies are funded by a Samvid Scholarship, which supports future leaders who aspire to drive change for society at scale. Ultimately, I hope to blend medicine with clinical research. I’m passionate about making a difference in patient lives, and I want to combine research and medicine throughout my career to develop solutions to pressing medical issues.