Neutron scattering research techniques that can show how nature uses complex protein structures to get cells to respond and adapt to stimuli in the body, could be the new tool to help researchers find new drugs to treat diseases such as heart failure or cancer Dr Jill Trewhella, a joint ANSTO* and Sydney University Research Fellow, said today.
Dr Trewhella, who recently returned to Australia after spending 25 years in the United States, is the world’s leading expert in using neutron scattering to study cell signalling systems which regulate the body.
“Healthy function in the cells that make up our bodies needs to have tight regulation of a multitude of interactions between biological macro-molecules such as DNA and proteins, often in response to external stimuli,” she explained. “To achieve this regulation, nature uses a number of small molecules as ‘messengers’ and these messenger molecules bind to target proteins to regulate their activities.
“By understanding the processes of how these messengers communicate their signals we can, for example, understand how healthy cells function and what is different in diseased cells.
“This detailed knowledge can not only help us understand how current drugs work but also help scientists develop more targeted treatments,” she said.
Dr Trewhella’s work focuses on the molecular details of signal transduction within cells: “It’s this understanding that can help us design treatments for disease such as cancer or heart failure, both of which involve a break down in regulation and signalling.
“Most of these signalling processes take place within milli-seconds, and many involve regulating the activities of enzymes called kinases which act as catalysts to enable phosphate groups to attach to proteins, which in turn signals to modulate their function,” said Dr Trewhella.
“Many drugs target kinases, so if we can understand how they change shape and adapt at the molecular level, we are on the way to really understanding how the body signals itself when it’s performing a simple operation like blinking, or when it’s sick and needs to recover.”
Dr Trewhella equates the neutron scattering techniques she uses to study the enzymes, to looking at black and white cats playing together on different coloured mats.
“Neutron scattering let’s you look at molecules interacting with each other by labelling one of them with an isotope, in this case substituting deuterium for all hydrogen atoms, so the neutron scattering profile is changed,” she explained.
“It’s a little bit like having a black cat and a white cat on a mat playing together: If you put them on a black mat you can see what the white cat is doing, and vice versa, but if you put them on a grey mat you can then see what each one is doing in the presence of the other.
“That’s the unique thing about this neutron scattering experiment, there’s no other technique which will allow you to do that and observe the shape changes of individual molecules when they are interacting in solution,” she said.
To carry out these types of experiments a cold neutron source is required and at present Australia does not have one. However once ANSTO’s OPAL reactor is completed at the end of 2006 this will change.
“One of the reasons for my returning to Australia was the fact that ANSTO will have a cold neutron source available for me to continue my work in this field. I am also very happy to be able to bring this important knowledge back into Australian science.
“Since my return to Australia in July, ANSTO researchers have already been approached to work on current cancer therapies using this unique neutron scattering approach although everything is currently only at proposal phase,” concluded Dr Trewhella.
Published: 01/12/2005