A zebrafish model of Ataxia Telangiectasia (A-T)

Dr Grierson

Research Project information

Principal researcher: Dr Andrew Grierson
Institute:  Sheffield Institute for Translational Neuroscience (SITraN) & The Bateson Centre, University of Sheffield
Cost: £88,710 over 36 months
Start Date: April 2017 (3 months no cost extension to June 2020 granted in February 2020)

Zebrafish are small tropical fish that are gaining popularity for academic and industry-led research into human diseases. Almost all human disease genes (approx. 70%) have an equivalent in zebrafish. While humans and zebrafish may not look alike, they are similar. Zebrafish are vertebrates (have a spinal cord) which is critical for modelling disorders of the nervous system such as A-T. Zebrafish are also highly fertile and it is possible to generate many fish in a short time.

What are the researchers proposing to do?
The aim of this project is to genetically engineer zebrafish carrying mutations in the gene, called ATM, that causes A-T in human patients.

There are limitations with conventional animal models of A-T as they do not develop the neurological characteristics that an A-T human patient does. To develop therapies or gain further insight into what goes wrong, researchers need to consider new models to investigate the mechanisms of A-T. The team want to study these fish in order to try and understand what “goes wrong” in the brain of A-T patients and use these fish to look for new therapeutic drugs that may slow down or limit the development of the neurological symptoms in A-T.

How will the research be done?
The team aim to produce genetically engineered zebrafish that carry ATM mutations using CRISPR-Cas9 gene editing techniques. CRISPR-Cas9 is a technology that has often been described as a pair of molecular scissors – it enables researchers to efficiently edit parts of the genome by removing, adding or altering sections of the DNA sequence.

How could it make a difference to the lives of those affected by A-T?
The researchers hope to use these fish to better understand the disease process, and eventually to test new therapies for future use in A-T patients. Currently, there are no therapies for A-T. This project aims to make progress towards the development of therapies by establishing a zebrafish model that develops A-T. If successful, thousands of drugs can be tested in the zebrafish, to look for drugs that might be beneficial in A-T patients.