Almost £400,000 has been awarded across four research projects working to better understand the basic biology of human asthma – without the use of traditional mammalian models.
The latest of the NC3Rs strategic award schemes has challenged scientists to approach asthma research questions in a completely novel way, encouraging them to seek alternatives to the mammalian lung that can be used in research to give valuable insights into how the disease manifests itself.
The scheme, which focused specifically on pioneering non-mammalian models for asthma research, has funded projects that will use fruit flies, zebrafish and, perhaps most surprisingly, a type of soil-living amoebae, known as a slime mould, to better understand how asthma is triggered and how new treatments may act.
Until now, the use of non-mammalian models in respiratory disease research has been almost non-existent. However, they have been used to gain an understanding of the molecular mechanisms of other diseases, and these mechanisms have been found to be similar in humans. This suggests that non-mammalian models may be useful alternatives for studying asthma.
Professor Robin Williams, from the School of Biological Sciences at Royal Holloway, University of London and Professor Sven-Erik Dahlén from the Karolinska Institute in Stockholm, will use slime moulds to explore how bitter tasting compounds cause airways that are constricted in asthma to relax, with the aim of identifying how potential new treatments for asthma might work at a cellular level to reverse or prevent asthma attacks.
“This project will provide a world-leading example of eliminating animals from basic and preclinical biomedical research, by employing a non-animal model for discovery and human tissue for preclinical translation,” Professor Williams explains.
Professor Margaret Dallman and her team from Imperial College London will study the response of zebrafish gills to substances thought to induce or exacerbate asthma, such as cigarette smoke or viruses. The zebrafish gill has never been used to understand and model a human disease, but lungs and gills are actually more similar in structure and function than may be commonly believed, so the approach has promise.
“Our approach aims to use a non-invasive tissue sampling method, as well as optical imaging techniques which can be used in the same animal over time, thereby reducing the number of fish needed, refining the sampling methods and producing more information per animal used. If our study shows that the zebra fish is a good model for asthma, this should lead to a reduction in the number of mice used in asthma research,” Professor Dallman said.
Advances in our understanding of the molecular mechanisms of asthma, could lead to more effective and safer treatments for patients. Asthma affects around 5.4 million people in the UK and 300 million people around the world. Asthma is a condition in which irritants can lead to inflammation, narrowing of the airways and breathing difficulties.
Projects funded by the ‘Non-mammalian models for asthma research’ strategic award:
- Developing a model for the study of respiratory inflammation in the zebrafish, Professor Margaret Dallman, Imperial College London, £99,830
- Developing a non-animal model system to investigate bitter tastants as new treatments for asthma, Professor Robin Williams, Royal Holloway of London, £99,988
- Use of Drosophila Models to Explore the Function of Asthma Susceptibility Genes, Professor Donna Davies, University of Southampton, £88,689
- A non-mammalian model to study innate immune modulation of airways remodelling in asthma, Professor Stephen Renshaw, University of Sheffield, £97,961
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