How Sweet It Is: diagnostic clinical and experimental glycoproteomics (2015–2018)

Most human proteins are modified by the addition of complex sugar groups, which are important for the correct function of these key biological molecules. N-glycosylation helps in protein folding and is important in development, cancer and the immune response. As a central cellular process affecting most secreted and membrane proteins, perturbations in the normal regulation of N-glycosylation can affect diverse proteins in many disease states. Understanding this complexity therefore calls for a systems glycoproteomic approach. In turn, the central place of Nglycosylation in cellular processes means that these glycoproteomic tools will be directly applicable to a wide variety of diseases. My vision for this fellowship is to develop a suite of robust mass spectrometry glycoproteomic analytics for use in conjunction with clinical cohorts, model systems and in vitro biochemistry to investigate fundamental aspects controlling N-glycosylation in diseases including oral carcinoma, T-cell immunodeficiency, diabetes and heart disease. Dysregulation of N-glycosylation in these conditions changes the extent of site-specific glycosylation at many sites in diverse proteins, with wide-ranging and complex consequences. I will study the mechanisms and biological roles of this regulation using clinical samples including blood and saliva, and model systems by developing a suite of mass spectrometry glycoproteomic analytic approaches integrating sample preparation, MS detection and bioinformatic analyses. This body of work will uncover the molecular mechanisms controlling glycosylation relevant to these conditions needed for therapeutics; and discover, validate and translate diagnostic and prognostic biomarkers of disease.
Grant type:
NHMRC Career Development Fellowship
Funded by:
National Health and Medical Research Council