Bringing asthma research into sharp focus

In some cases of asthma, the disease is so severe that sufferers don’t respond to drug treatment. It’s thought this is due to structural changes in the lungs, which can prevent conventional therapies from working. Dan Richards talks to NC3Rs David Sainsbury Fellow, Dr Amanda Tatler, University of Nottingham, who is looking for new drug targets by applying an approach to measure lung function that has seen little use in asthma research, and uses more than 80 per cent fewer animals than conventional methods. If successful this could significantly reduce the use of animals across the whole asthma field.

Dr Amanda Tatler

What is your NC3Rs-funded research about?

My research is focused on the extremely common respiratory condition asthma. While the majority of asthma patients are well controlled on currently available treatments, around 10 per cent of sufferers have a severe form of the disease that is often unresponsive to therapies. In recent years there has been evidence to suggest a link between recurrent bronco-constriction of the airways in asthma and the development of structural changes in the lungs, which have a detrimental effect on lung function.

My research aims to establish the mechanisms driving this process in order to highlight potential new therapeutic targets in asthma using a 3Rs approach. There were greater than 600 publications last year alone using mice in asthma research – highlighting the need to apply the 3Rs to research in this field to reduce animal use. By using state-of-the-art imaging techniques, such as functional magnetic resonance imaging (fMRI), and an ex vivo precision-cut lung slice model of airway contraction, I am reducing the number of animals needed to allow me to effectively test my hypotheses.

Watch: An airway contracting in a precision-cut lung slice

How does your 3Rs approach reduce the number of animals used for this type of research?

The ex vivo precision-cut lung slice model that I’m using mimics the repeated contraction of the airways seen in asthma. This model allows me to test several different broncho-constrictors and also different potential therapies in a single animal. More than 40 separate lung slices can be obtained from an animal. This allows me to perform multiple experiments on a single animal, reducing the number of animals required in this set of experiments from 96 to just 12 – a reduction of 88 per cent. Not only does this technique significantly reduce the number of animals needed to answer my research question but it also improves the consistency of my data and decreases experimental variability simultaneously.

I am also striving to replace current methods of measuring lung function in experimental animals with state-of-the-art imaging such as fMRI in collaboration with Prof. Meersman at the Sir Peter Mansfield Magnetic Resonance Centre at the University of Nottingham. It is my hope that the conclusions I reach as part of my fellowship and the techniques that are developed could be disseminated around the asthma and respiratory research communities, ultimately leading to a great reduction in animal use across the whole field.

Why did you apply for the NC3Rs David Sainsbury fellowship?

Since starting to work on in vivo models of respiratory diseases a couple of years ago I have constantly tried to apply the 3Rs to my research. Animal research is often seen as necessary in my field, but it’s always important to find new methods to reduce animal use. The NC3Rs fellowship was perfect for me since it allows me to address an important question in asthma while also working to reduce animal usage and promote the 3Rs in my research.

How has the experience been so far?

My experience of being an NC3Rs David Sainsbury fellow has been fantastic, and has allowed me to begin to carve a career for myself as a successful independent researcher. The University of Nottingham has been extremely supportive in my transition and acknowledged my achievements by making me a senior research fellow. The support that the NC3Rs gives to me is unbelievable and they have invited me to present to a panel of high-profile scientists in the asthma field about my work. My international reputation is growing rapidly thanks in part to the exposure that being an NC3Rs fellow brings.

What motivated you to become a scientist?

From an early age I was passionate about science, particularly biology. I am excited by new ideas and the thrill of discovering the answer to an important question that has not previously been answered. I am a naturally curious and inquisitive person and love to constantly learn new things, traits that I think are fundamental to being a scientist. I find working in medical research extremely rewarding knowing that the work done in our laboratories can impact patient care and clinical treatments.

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