Investigating the role of the O-GIcNAc post-translational modification in protein function and specifically in the etiology of type II diabetes

Sequencing the human genome has led to the realization that a relatively small number of genes can give rise to an enormously complex living organism. This can be explained by the fact that proteins can be modified after their initial assembly to have multiple functions in multiple locations in the co-ordination of cell growth and function. One such modification called O-GlcNAc has been shown to be involved in many cellular processes, however, its precise function has not yet been determined. Malfunctions in the regulation of O-GIcNAc-modified proteins have been implicated in such diverse diseases as diabetes, Alzheimer’s, Parkinson’s, and a variety of cancers. For example, diabetic patients have been found to have elevated O-GlcNAc levels, although it is not clear whether these high levels are a cause or an effect of diabetes. Using techniques including mass spectrometry, chemical synthesis and mouse models, Matthew Macauley’s goal is to develop a method for identifying proteins modified by O-GlcNAc. This will give valuable insights into how this modification process affects normal cell function and may provide new knowledge about its precise role (i.e. is it a cause or an effect) in diabetes. In turn, such knowledge may contribute to the development of more effective preventive and treatment strategies.