The Stapleton laboratory is interested in understanding molecular insights into how specific proteins bind to carbohydrates. These proteins attach via a region known as the carbohydrate-binding module (CBM).  There are over 50 different CBM families in many different types of organisms, ranging from bacteria to plants to humans, that bind to various carbohydrates like starch, cellulose and glycogen. 

We are focussing on one CBM family (CBM48) that is found within an enzyme called AMPK, a metabolic regulator that couples many physiological events to metabolism. For example, activation of AMPK in muscle leads to increased glucose uptake, fatty acid oxidation and insulin sensitivity, making AMPK a potential drug target for the treatment of Type II diabetes.  We are in the process of determining the 3-dimensional shape of these CBM48 proteins using both NMR and X-ray crystallography, together with determining what part of the glycogen molecule they specifically bind to and how tightly. 

The Stapleton group also focuses on the biology and biochemistry of glycogen. Little is known about glycogen, even though it is essential for maintaining our blood glucose levels.  There are many diseases, including cancer and Type II diabetes, where glycogen levels are abnormal but the molecular reasons are unclear. Therefore, we are using new technologies like cryo-electron microscopy and mass spectrometry to better understand how glycogen is made and to identify new glycogen-associated proteins in health and disease.  Together, the research activities of the Stapleton laboratory may lead to the identification of new drugs for the treatment of diseases like Type II diabetes.

Techniques include: mass spectrometry: LC-Ion Trap, LC-QTOF, cryo-electron microscopy, glycogen purification mammalian cell culture, protein expression, NMR and X-ray crystalography.

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David Stapleton Bio

David Stapleton commenced his PhD in Prof. Bruce Kemp's lab in 1992 at St. Vincent's Institute of Medical Research.  Between 1992 and 1996, he was part of team that purified and cloned AMP-activated protein kinase (AMPK). He travelled to Tony Pawson's laboratory in Canada in 1997, as a NHMRC CJ Martin Fellow, to work on a project identifying how nerves grow, from A to B, in a developing brain.  In 2000, David returned to St. Vincent's Institute to set up his own laboratory and soon was awarded an NHMRC RD Wright Fellowship together with a NHMRC Project grant working on the structure and function of the AMPK regulatory sub-units.  This led to the identification and 3-dimensional structure of a carbohydrate binding module within AMPK. In 2005, he moved his laboratory to the Bio21 Institute to continue his research on carbohydrate-binding modules and began exploring glycogen-associated proteins in health and disease. 

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Stapleton Research Group

Postgraduate  Students

• Ms Ann Koay

Honours Students

• Ms Cathy Accurso
• Mr Shane Emanuelle

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