David Rose carries out research in structural glycobiology with particular interest in enzymes associated with human health and disease. Recent work focuses on enzymes that take part in processing major components of the human diet.
Office: STC 4042
Phone: 519-888-4567, ext. 30509
Lab: ESC 244, ext. 31217
- Bioinformatics, Systematics, and Evolution
- Molecular Genetics
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.
Professor Rose teaches both undergraduate and graduate courses. Course offerings have included
- BIOL 486 Glycobiology
- BIOL 499 Senior Honours Research Project
- BIOL 680 Graduate Special Topics
- BIOL 650 Biomolecular Techniques
- Campbell RL, Rose DR, Sung WL, Yaguchi M, Wakarchuk WW. 'Construction of Thermostable Mutants of a Low Molecular Mass Xylanase', U.S. Patent 5,405,769 Apr. 11, 1995.
- Van den Elsen, J, Kuntz DA, Rose DR. ‘Structure of Golgi a-mannosidase II and complexes’, September, 2001.
Awards and Distinctions
- Fellow, American Crystallographic Association
University of Waterloo Affiliations
- Water Institute
- Steering Committee, Centre for Bioengineering and Biotechnology
- Steering Committee, Chronic Disease Prevention Initiative
- CIHR University Delegate
Professional Associations and Service
- Chair, Terry Fox Research Institute New Frontiers Program Project Grant Steering Committee on Research Excellence
- American Crystallographic Association
- Canadian Society for Medical Biosciences
1981 PhD Molecular Biophysics, University of Oxford
1977 BA Biophysics, University of Pennsylvania