In his new state-of-the-art microbiology lab, Professor Serge Mostowy manoeuvres what might be the world’s smallest syringe towards tiny zebrafish embryos.
“There” he says, indicating the microscope lens, his enthusiasm infectious “You can see the bacteria spreading, you can see the immune system responding. It’s right there in front of your eyes.”
A walk down the corridor takes us to the source of these embryos. It’s more like an aquarium than a lab, with hundreds of small tanks full of adult zebrafish. But a closer look shows this is no tourist attraction. Tanks labelled with terms such as “CD41 + GFP”, show how each group of fish has undergone gene editing to allow the study of different biological responses to infection.
“We’re just interested in the embryos” says Prof Mostowy, who leads a research group at the London School of Hygiene & Tropical Medicine (LSHTM). “We leave the adult fish to swim around, eat and mate.” A team of animal technicians keeps them fed, and each morning embryos are collected for study. “We have to get in quickly to collect them early during their development”, he adds.
As we return, Prof Mostowy points to a locked door, “that’s our new laboratory. Some of the pathogens we study are seen as dangerous in the wrong hands, so we need to meet strict rules to study them.” After a pause, he adds “But then, they can be also dangerous in nature, so we need to study them, and there aren’t many places in the UK where I can do this work.”
The use of zebrafish is an emerging approach to studying infection, and one Prof Mostowy has helped to pioneer. “In the first days of a zebrafish’s life, it is completely translucent” he explains excitedly. “So, we can actually see under a microscope what biological processes are happening in a live environment. You can’t do that in a mouse because it has skin and fur, but you can in a zebrafish.”
“This gives us phenomenal insight into what’s actually happening at a biological level when infection enters our body. And thanks to advances in microscopy” – he gestures to an impressive looking piece of kit labelled ‘Zeiss laser-scanning-confocal-microscope with Airyscan’ – we can actually observe how pathogens interact with cells at a molecular level. If we understand the mechanisms different infections use to attack our cells and multiply, that’s the first step to finding targeted ways to stop them.
This approach - of studying the fundamental biology of infection and developing responses aimed at individual pathogens - is attracting growing interest from global health programmes. Overuse of antimicrobials has led pathogens – bacteria, viruses and parasites - to evolve resistance. Resistance to antibiotics – the group of antimicrobials used to treat bacterial and some parasitic infections – is a particularly pressing problem, and antibiotics can also have unwelcome side-effects. Antimicrobial resistance (AMR) is considered by the World Health Organization to be one of the biggest threats to global health we are currently facing. If antimicrobials - our main weapon in the battle against infectious disease - become ineffective, we will face a health crisis not seen since the dawn of modern medicine.
Words by David Lewis for LSHTM
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