Melbourne Team makes landmark biomedical discovery
 
A team of Australian scientists has won the race to determine the three dimensional structure of an important protein molecule in humans.

The protein - the epidermal growth factor (EGF) receptor - was detected on cancer cells over 20 years ago and laboratories all over the world have been trying to understand how it works ever since.

The medical implication is that solving this structure provides the detailed information for the discovery of a new class of anti-cancer drugs based on rational drug design.

These drugs would be designed to bind to the receptor and block its activation by growth factors.
 
The research team consists of scientists from the 'Parkville biomedical strip' in Melbourne: CSIRO Health Sciences and Nutrition, Walter and Eliza Hall Institute of Medical Research and the Ludwig Institute for Cancer Research, all members of the Collaborative Research Centre for Cellular Growth Factors. Their findings will be published in the September 20 issue of the international journal 'Cell'.  Click the following to see relevant MEDLINE/Pubmed abstract link for this article: 'Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha'.

"This is a landmark discovery made amidst considerable International competition," says Dr Colin Ward of CSIRO Health Sciences and Nutrition.

In 1997 a group of Melbourne scientists formed a large team to tackle the problem. Their combined efforts have revealed an intriguing structure which is already challenging the current views of cell signalling.
 

Dr Tom Garrett of the Walter and Eliza Hall Institute of Medical Research says the discovery represents a major breakthrough.

"This structure turns receptor biology on its head," he says. "We have shown that these molecules communicate in different and more subtle ways than had been thought."

The partners are now using the 3D-structure of the EGF receptor to gain further insight into the way it works and to identify potential drugs to act as inhibitors. 

"The EGF receptor structure contains a number of surprises which have already pointed the way to new approaches to designing drugs to interfere with the activation of this receptor in cancer cells," says Dr Tony Burgess of the Ludwig Institute for Cancer Research. 

The discovery follows on from long-term research by CSIRO and the Biomolecular Research Institute into the structure of similar proteins.

Note:

Growth factors are proteins that control the everyday function of cells in the body. However some diseases such as cancer and psoriasis are associated with abnormal activity of these growth factor driven processes. One such growth factor is the epidermal growth factor (EGF) which stimulates cells by binding to a large protein on the surface called the 'epidermal growth factor receptor'. The EGF receptor was the first of its type to be discovered and there has been intense interest and activity around the world to understand the molecular details of its structure and the way it binds EGF.

More information

Warrick Glynn, Communication Manager
Parkville, CSIRO Health Sciences and Nutrition 
+61 3 9662 7344, Fax: +61 3 9662 7223, 0408 117 846
 

Dr Colin Ward (research into the protein structure)
Program Manager - Protein and Pharmaceutical Sciences
CSIRO Health Sciences and Nutrition
+61 3 9662 7291, Fax: +61 3 9662 7101
 

Prof Tony Burgess (implications of the discovery for cancer research)
Director, Ludwig Institute for Cancer Research 
+61 3 9341 3155
 

Dr Tom Garrett (molecular modelling of protein structure)
Walter and Eliza Hall Institute 
+61 3 9662 7311