David R. Rose

Professor (Department Chair)

Professor David RoseBachelor of Arts (BA) Pennsylvania, Doctor of Philosophy (DPhil) Oxford

Email:  david.rose@uwaterloo.ca

Telephone: (519) 888-4567 ext. 35208

Office: Earth Sciences Building (ESC) 349

Lab: ESC 244, ext. 31217

Research interests

Structural Studies of Glycoside Hydrolases
This major area of research involves enzymes that recognize and act upon carbohydrates, including especially glycosidases involved in the protein glycosylation pathway and the process of starch digestion.

Intestinal Maltase-Glucoamylase and Sucrase-Isomaltase (MGAM and SI)
MGAM and SI are involved in starch breakdown in mammalian cells. Inhibition of these and other alpha-glucosidases is proposed to be a novel approach to treatment of Type II Diabetes. We have expressed these Family GH31 enzymes in Drosophila cells and studied the activities of a series of specific inhibitors under development as anti-diabetics. We have determined the crystallographic structure of two of the four GH31 domains of these enzymes.

Gut commensal microbial glycoside hydrolases
The human intestine is populated by many bacterial species in a symbiotic partnership. One of the roles for these bacteria is in the digestion of resistant starches that have survived the intestinal MGAM/SI processing, as a source of nutrition for both the host and the bacteria. We are interested in a structural approach to studying the mechanism of recognition of resistant starch structures by the bacterial glycoside hydrolases. Of the gut bacteria with known genomes, Bacteroides thetaiotamicron has the largest number and variety of predicted glycoside hydrolases, suggesting that it plays a key role in salvaging resistant polysaccharides such as starch. We are building on our results on the intestinal enzymes to express and purify family GH31 enzymes from Bacteroides thetaiotamicron with the goal of studying their substrate specificities and, hence, defining their role in nutrition.

Selected recent publications

Affiliation: 
University of Waterloo

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