Read and watch some examples of how animals are used in research at Imperial.
The amphibian plague
Around the world, frogs and other amphibians are facing rapid population decline and extinction – largely due to an aggressive fungal parasite. In this video Professor Matthew Fisher from Imperial’s School of Public Health explains how his work in the lab to help these animals is being successfully carried into the wild.
Ferrets and the flu virus
Each year millions of people are infected with flu and hundreds of thousands die as a result of the infection. In this video, Professor Wendy Barclay explains why researchers use ferrets to study the flu virus and the role ferrets are playing in preventing infections round the world.
Mice sleeping patterns and anaesthesia
General anaesthesia is routinely used to enable patients to withstand medical procedures that would otherwise inflict unbearable pain and result in unpleasant memories. In a similar way to anaesthesia, sleep is also characterized by altered consciousness and greatly reduced responses to sensory input. Despite the fact that sleep is one of the most powerful physiological drivers of behaviour and it clearly provides an essential biological need (long-term total sleep deprivation can cause death in rodents faster than food deprivation), exactly how sleep is triggered, and how it affects the neurological pathways of the brain is still a mystery.
Rodents have been the most widely used model organisms in biomedical research for many years and their use has proved invaluable to understand the complexity of how receptors and channels influence brain physiology and generate sleep, or respond to anaesthetics to produce unconsciousness. With their genetic, biological and behavioural characteristics resembling those of humans, mice represent a powerful model to study the brain circuits. Genetic engineering of mice allows testing specific hypotheses regarding the importance of particular molecular targets or the importance of particular brain circuitry.
Professor Nick Franks and Bill Wisden’s research at the Imperial College focuses on the relationship between general anaesthesia, sleep and sedation. In their studies the two scientists theorise that the sedative and hypnotic actions of general anaesthetics may be mediated through overlapping neuronal pathways that control natural sleep. Their results could lead to the development of new drugs with fewer side effects and which might give the restorative benefits of natural sleep.
‘Anaesthesia and sleep are both commonplace states that involve a reversible loss of consciousness, but we don’t understand how either works: every year, 250 million patients worldwide are given anaesthetics; and every day, at some point in the 24-hour cycle, all humans and animals require sleep. Our research suggests that sedation and deep sleep are intimately connected at the circuit level. Understanding how they interlink is important for both fundamental neuroscience and medicine’, says Prof Franks.
By exploiting what is known at the molecular level, their research should provide insights into both how natural sleep is regulated, as well as how and where general anaesthetics act at the level of neuronal networks.
Zebrafish: windows to cell biology
Young zebrafish are transparent, their skin and internal organs as clear as glass. This makes them remarkable subjects for research. With the aid of dyes and fluorescent tags, scientists use a microscope to see how their organs and even individual cells function, in an entirely non-invasive way.
Comparable observations of organs are very hard to achieve in mammals such as mice. "The procedures are very invasive, very complicated and don't get the same kind of data," says Dr Laurence Bugeon, who uses zebrafish to study inflammation.
And at the cellular level, it is almost impossible to get the same results. "There are fantastic scientists on the planet using the mouse model, but they cannot see what we can see using the zebrafish model," says Dr Serge Mostowy, who uses the zebrafish to study how cells react to bacterial infection.
"What we can see is absolutely remarkable," he goes on, "not only at the whole animal level, but you can look at the single cell level, you can also look at the single bacterium level, and you can do this in a living organism, in real time."
Zebrafish also turn out to be a remarkably good model for research into some aspects of human biology. For example, their innate immune system – the first line of defence against infections – is very close to that found in humans.
Dr Mostowy uses zebrafish larvae that are five days old or younger to study how cells respond to infection. "We've engineered transgenic fish in which proteins or cell types are labelled with fluorescent colours, and we can also infect these larvae with bacteria of different colours. Then we can watch the orchestration of host-pathogen interactions in real time using high resolution microscopes."
He is particularly interested in Shigella flexneri, a bacteria responsible for a form of dysentery in humans, which he showed can also infect zebrafish cells. Shigella kills over 1 million people per year, particularly in the developing world. It is also becoming increasingly resistant to existing anti-microbial drugs. "So we are looking for new and unique ways to control the bacterial infection."
The similarity also extends to the way the fish's intestine deals with cholesterol. This allowed Dr Bugeon and her colleagues to watch as the fish's immune system responded to a high cholesterol diet, sending immune cells tagged with fluorescent markers to the gut.
They also filmed the muscle contractions, called peristalsis, that move food through the intestine. "This is a very complex movement, and you cannot image that in a mouse. But in the zebrafish, especially at a very early stage, we have beautiful videos of this peristalsis. And we found that it was affected after a high cholesterol diet," she says.
The next step is to understand the cause behind this effect, and to relate it to the disruption movement associated with gut inflammation in humans.
Dr Bugeon works with older larvae and adult fish, since the organs that interest her have to be fully developed. "The larvae may only be 2 millimetres long, but they are regulated," she says. "That means we have to apply for every procedure that we do, and care for the fish in the best way we can."
She insists that using zebrafish should be seen as a refinement of animal procedures rather than replacement. "An adult fish is the same as a mouse. It can experience pain as well, and so we have to consider it in the same way," she says. "Just because fish are not furry and warm, it doesn't mean that we don't care."