Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

In nature, proteins are commonly modified by the attachment of sugars in a process known as glycosylation. Glycosylation of proteins is important and different sugar structures can have different effects. One of the most well-known sets of sugar structures are the blood-type determining ABO antigens. O blood is often called the universal donor because it can be transfused into any individual. Thus, it is often used in emergencies and is in the highest demand. The supply of O blood would be improved if A- or B-type blood could be converted to O-type. While there exist enzymes that can convert A or B blood to O blood, they are too inefficient to work at the needed scale. Besides blood groups, glycosylation can dictate many aspects of a protein's function including the activities it carries out, how long the protein survives, as well as how its recognized within the body. Because many drugs are glycosylated proteins, the ability to manipulate their glycosylation (both taking sugars off and putting new sugars on) using enzymes would allow for improved study of the roles of specific sugar structures as well as open the door towards "optimal" protein glycosylation. The focus of my research is then to identify enzymes which can cleave sugars from proteins. I will identify such enzymes from the 10-100 trillion microbes which reside within the human gut. Many of these microbes provide a benefit to humans through digestion of carbohydrates that we cannot digest ourselves. Nevertheless, the mucous membranes of the gut carry a high density of glycosylated proteins. Some gut bacteria then digest these mucosal sugars for energy in order to gain a competitive advantage. My research will aim to identify some of these bacterial enzymes involved in the cleavage of mucosal sugars. Once identified I will harness their abilities for the improvement of drug glycosylation as well as the production of O-blood.