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The University of Southampton
Biological Sciences

Research project: Use of Drosophila Models to Explore the Function of Asthma Susceptibility Genes

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Asthma is a complex disease that involves both environmental and genetic contributions. To elucidate the role played by these factors there is a need to study their contribution in a genetically tractable model organism.

Over the last 10-15 years considerable progress has been made in identification of around 100 asthma susceptibility genes using a variety of genetic approaches including large genome-wide association studies (GWAS). However, despite substantial advances at the genetic level, the functions of many of these genes and/or how their genetic polymorphism contributes to asthma remain poorly understood, especially for those genes involved in local tissue susceptibilities such as barrier immunity and tissue remodelling. Furthermore, it is now widely accepted that the genetics of asthma and allergic diseases are multifactorial. No single gene or genetic variant can explain all or even most variances in the general population for asthma and allergic diseases.
Traditionally, approaches for understanding gene function rely heavily on use of murine models to delete and/or over express the gene of interest. However, such approaches are costly, time consuming and may result in absence of a quantifiable. Therefore, there is a need to develop alternative approaches that reliably speed up the screening process and offer potential for introducing several disease-genes into the same organism to allow assessment of gene-gene, as well as gene-environment effects. The fruit fly, Drosophila melanogaster, has proved to be a useful genetic tool for studying a number of human diseases including neurodegeneration, cancer, metabolic disorders and cardiovascular disease. These flies provide a high throughput tool with conservation of basic cellular pathways, have excellent genetic tractability and in vivo imaging capabilities. Crucially, they also have branched airways (tracheae) with similarities to human airways. We wish to test the hypothesis that Drosophila models can replace, augment and inform vertebrate asthma models by allowing first-pass elucidation of key asthma genes, as well as providing an in vivo model for rapid high through-put drug screening.

Funding: NC3Rs

Funding duration: 2015

Related research groups

Biomedical Sciences
Clinical and Experimental Sciences
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