Something To Twist and Shout About

A team from the Embryology Unit at Children’s Medical Research Institute has untangled the twisted threads of a story about a gene, aptly named Twist , that is proving to be a key player in the development of both head and limbs in an embryo. 

In humans, mutations in Twist cause a rare disorder called Saethre-Chotzen syndrome (SCS) which is associated with malformations of the face and skull (craniofacial) and extra or missing fingers and toes.

Although SCS is very rare, understanding the genetic pathways behind the syndrome is key to understanding many similar disorders. “There are a large number of human syndromes in which we see both craniofacial and limb abnormalities together,” says Dr David Loebel, a post-doctoral scientist in the laboratory. “We now have strong evidence, that Twist is a central co-ordinator for several pathways of interacting genes that choreograph head and limb development. Because the paths are interlinked a mutation in any one of these genes would lead to similar malformations.”

The product of the Twist gene belongs to a group of proteins known as transcription factors that switch other genes on and off. The team has used several different approaches to discover which genes Twist is regulating.

Studies on the effects of mutating Twist in mice have confirmed that the gene is essential for normal development of the head and limbs, indicating that Twist has a major effect on two key molecules that mediate communication between cells. CMRI scientists have confirmed that Twist directly controls two genes, Alx3 and 4, previously suspected to have a role in the Twist line of command due to the similar abnormalities the genes cause when mutated.

Dr Loebel’s role in the project has been to hunt for new genes that form links in the chains leading out from Twist’s control hub. “We were extending the study beyond preconceived hypotheses of genes suspected of operating in the same pathway, to discover entirely new genes.”

    
And in a twist of classic timing Chubby “Let’s Twist Again” Checker has donated his jeans for this year’s Jeans for Genes© Celebrity Art Auction.  Sydney artist Ernie Gerzabeck has created a stunning brightly coloured canvas incorporating Chubby’s jeans as part of the unique collection of celebrity jeans to go under the hammer at Dockside, Darling Harbour on July 24th.

This year is the 10th anniversary of Jeans for Genes Day – the campaign that is the main fund-raiser for Children’s Medical Research Institute – and it is hoped around $4 million will be raised for this kind of cutting edge research being undertaken by scientists at CMRI.

     
Chubby Checker probably never envisaged his jeans would one day be used to raise the essential funds needed for researchers like Dr. Loebel and the team to continue their ground breaking work.
 

Jeans for Genes Day© is on Friday August 1 when millions of Australians will don their jeans and buy a badge or make a donation to CMRI.  And some will no doubt be bidding for the Master of the Twist’s jeans!