Zebrafish Enable Paediatric Research

Posted on: 15 January 2010

Zebrafish are being used in TCD paediatric research to shed light on the genetics of a bowel defect called  Hirschsprung’s disease that affects one child in every 5, 000 Irish births. The only treatment for this condition to date is surgery. The interest in this project arose as TCD PhD student in paediatric research, Dr Reshma Doodnath, has worked in paediatric surgery, and has dealt with patients that have this disease, along with their families.  “If a baby doesn’t have a dirty nappy within the first 48 hours, our first index of suspicion is Hirschsprung’s disease,” says Doodnath who has performed surgery on such babies.

There are many genes that are thought to be involved in the disease although many remain unknown. The aims of the project are to determine the expression and function of a class of genes called Homeobox genes in the development of the enteric (or intestinal) nervous system  of zebrafish.

The Zoology department, within the School of Natural Sciences, is significantly involved with this project. Dr Michael Wride who is supervising the project, is a lecturer in Zoology and is leader of the Ocular Development and Neurobiology Research group. “If we can figure out how Homeobox genes influence enteric nervous system development, this would be the first step to develop stem cell-based therapies for Hirschsprung’s disease for example, but this is not going to happen soon; much more basic work, like that we are carrying out, is required on the fundamental developmental events is required,” says Wride.

The majority of genes in humans also exist in zebrafish, and the vast majority of these genes perform the same or a similar function. Early development of zebrafish embryos is external, rapid and visually accessible. Because the protective membrane surrounding the embryo is transparent, the scientist can follow development from the moments of fertilisation through to free swimming, actively feeding larval fish.  The millimetre-sized embryos form a functional gut within days, and specifically in relation to Dr Doodnath’s paediatric research the gut can be observed through a microscope because the embryos are transparent.

As seen in the Irish Times.