Virtual reactions

Issue 20 | Spring/Summer 2007

Report: Andrew Shaw
Photography: Melissa Di Ciero and Greg Ford

Dr Sarah Boyd's interest in science and IT was the genesis of a computer program that simulates the body's enzyme-protein interaction

Monash scientists are uniting once disparate disciplines, designing complex computer simulations to fast-track work once confined to the laboratory.
Dr Sarah Boyd has created a virtual model that replicates part of the body's immune system, a development that has taken her halfway across the world.

What do you do when you're passionate about two disciplines and are asked to choose one? That was the dilemma faced by Dr Sarah Boyd when she started the Monash Science Scholar Program, a degree course for outstanding students.

"I was interested in computers, but I also loved the biological sciences," Dr Boyd said. "I didn't know which one I should give up. Then my adviser said I shouldn't give up either, and told me about this really exciting new science called 'bioinformatics' - using computers to do biological research."

While juggling a timetable between the faculties of Information Technology and Science, Dr Boyd became interested in proteins, particularly the way they function in the immune system. The regulation of proteins is fundamental to life and must be tightly controlled.

Nature does this by cutting proteins in two with enzymes called proteases, a process that either activates or deactivates the proteins. A dysfunction in a protein or its protease can result in a multitude of diseases, including inflammatory disease, autoimmune disease and cancer, and opportunistic diseases caused by bacteria and viruses.

Dr Boyd developed the Prediction of Protease Specificity (PoPS) project that remains the core of her research. In the PoPS environment researchers explore how proteases interact with and control proteins. The program takes data about proteins and proteases and simulates an interaction.

In January, Dr Boyd received a three-year Australian Research Council grant to research more complex models of protease function. She is currently a visiting researcher at San Diego's Burnham Institute.

"If you can create a simulation of the system you are trying to study, you can explore that system in order to investigate what's happening," Dr Boyd said.

"Of course, it depends on how good your simulation is. But given at least a reasonable simulation, you can use the computer to help formulate the 'educated guesses' to direct the laboratory experimentation."

PoPS has been used in projects investigating peanut allergy, cancer, gingivitis and inflammatory disease. In addition, proteases are used in dairy, leather and detergent products, and Monash is developing a plan to commercialise PoPS' scientific gains.

Dr Boyd has also developed a model of the Der p 1 protease from the house dust mite, Dermatophagoides pteronyssinus, one of the most potent allergens known.

"It was suspected that Der p 1 was targeting immune system proteins. Cutting these proteins would result in the inflammatory response that sufferers of dust mite allergy would be painfully familiar with. Using the modelling and simulation tools of the PoPS system, we identified two particular proteins, DCSIGN and DC-SIGNR, which have been shown experimentally to be cut by Der p 1. As a result, these are now implicated in the initiation of an allergic response." But it hasn't all been plain sailing, according to Dr Boyd.

"When I first proposed the idea, some people were very supportive, but I also met with a great deal of scepticism and concern that I was chasing a long road to nowhere," she said.

"The biggest argument against PoPS has been, quite simply, 'You can't do that, it's too hard.' In protease biology it's well known that protease function is a very complex model, believed to be too complex to even tackle in the laboratory.

"However, at Monash we have already demonstrated that it's possible to computationally identify proteases that don't follow the simple model, and that it is possible to tackle this problem in simulation and in the laboratory."

Dr Boyd describes the use of computer science in medical and other research as "a new wave" of technology, one that will see a blurring of boundaries between disciplines.

"Specialising in a single discipline is the paradigm of research, but this will change as cross-disciplinary research becomes standard. Computer science crossing over with other disciplines is one really good example of that.

"We are contemplating a very likely future where huge amounts of research are planned and simulated in computers before we even get to the laboratory bench. It's not the magic bullet, but it is an extremely valuable tool that we are adding to the collection."

For more information, please see Dr Boyd's web page.