Hydrodynamic forces tapped for therapeutic purposes

Novel hydrodynamic modelling is helping to unravel the forces behind the life-threatening clumping of human proteins that can trigger type 2 diabetes, Alzheimer’s disease and Parkinson’s disease, as well as many other conditions.

When proteins in human blood and cells incorrectly lose their shape and unfold into flat sheets they can clump together to form amyloid fibrils.

Although fibrils are a medical issue, it is Professor David Dunstan of the University of Melbourne’s Department of Chemical and Biomolecular Engineering whose research is producing vital new insights into how they form.

He has developed novel laboratory-based methods to monitor proteins as they unfold in real time, in response to hydrodynamic forces of fluid flows, such as blood circulation.

His approach is of particular interest to biotherapy companies and he is working with CSL Limited on a project to study the unfolding of a blood protein, Von Willebrand factor.

The unfolding of this protein plays an important role in triggering wound healing. It also triggers the formation of blood clots, or thrombus, during a heart attack. Left unchecked, the thrombus can cause a lethal block in the supply of oxygen to the heart.

“We want to understand and ultimately develop therapeutics to control the unfolding and activation of Von Willebrand factor and clot formation,” Professor Dunstan says.

“So these are products that can turn clotting on and off, particularly in the case of coronary thrombosis but also with potential benefits to haemophiliacs.”

Von Willebrand factor is known to unfold in certain flow conditions that Professor Dunstan can mimic using his unique blend of physical chemistry and rheo-optics.

With CSL Limited, he uses this unique capacity to understand protein unfolding and monitor the impact of potential therapeutic products while screening for compounds that could one day improve outcomes for heart-attack patients.

More information

Prof David Dunstan davided@unimelb.edu.au

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