Examples of animal research
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.
Fruit flies signal new discoveries
For more than a century, fruit flies – Drosophila melanogaster – have been used to investigate how genes control the development of single cells into complex bodies. The more recent practice of using them to study physiological changes has opened up new lines of research, and reduced the need to work with higher animal models such as mice.
Just as humans share 60 per cent of their genes with the fruit fly, there are also similarities between human and fly intestines. Both, for example, contain stem cells that help replenish the lining of the gut, building it up if required or repairing damage.
Discovered almost 20 years ago, this similarity has prompted a thriving line in research looking at subjects such as nutrition, stem cell biology and how the intestine deals with tumours. But not, until Dr Irene Miguel-Aliaga’s research, the nervous control of the gut.
"This work with Drosophila is a pretty powerful approach, because you can combine genetics with physiology and see the mechanisms underlying how tissues adapt, not just how they are made," says Dr Miguel-Aliaga.
Its work has produced some fascinating discoveries. Looking at the neurons themselves, the group has identified a sub-set that interacts with the system of tubules that distributes oxygen throughout the fly's body. "These neurons talk to this system and regulate the branching of the cells that deliver oxygen to the gut, and that seems to matter in adaptations to malnutrition," she says. "So this is a new mechanism that we have been able to find in flies and which might apply to humans and to their vascular systems."
Dr Miguel-Aliaga and her team have also looked at the characteristics of the gut and its lining, the epithelium. This has produced a surprising finding. "Males and females – whether flies, mice or humans – have different sex hormones, and that makes us different and makes organs in males and females function differently," she explains. "What we found in the fly is that the intestine has an intrinsic sexual identity, so the cells of the epithelium know whether they are male or female."
This opens up all sorts of interesting questions for further research. For instance, might this intrinsic sexual identity play a role in the different way males and females develop cancers? The stem cells of female fruit flies divide and multiply more readily than those in male flies, and when a fly's genes are manipulated so that it develops tumours, females develop many more than males.
"This tells you that there are also sex differences in tumour susceptibilities," says Dr Miguel-Aliaga, adding that this mirrors the incidence of human cancers. "People have traditionally ascribed this to sex hormones, but I think that, based on the fly data, it would be very interesting to go back to humans or to other model systems such as mice, and see whether there is some sort of intrinsic component to these differences in susceptibility."
Another area of investigation that she would like to explore in more complex animals is the observation that the intestine increases in size when female flies are laying lots of eggs. Rather than neurons, this change is down to a hormone. Released when the fly is laying eggs, the hormone appears to prepare the fly's body for the additional energy demands of reproduction. This research has the potential to tell us more about how hormones prepare women's bodies for pregnancy and recovery after giving birth.
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."