Dean Tolan

Understanding the structure, function, and mechanisms of eukaryotic aldolases, and other enzymes involved in fructose metabolism is the goal of our research. There are three approaches being considered to answer these questions: (1) recombinantly expressed enzymes and their variants expressed in microorganisms will be used to biochemically characterize these adolases; (2) recombinant aldolase genes, as well as others involved in sugar metabolism, from distantly related species will be isolated and characterized for sequence comparisons; (3) the generation of an aldolase B “knock-out” and/or “knockin” mouse, as well as others involved in sugar metabolism, and the expression of HFI-causing mutant aldolases; and the cloning and characterization of other genes from mice that are involved in fructose metabolism. One major approach involves the use of human subjects suffering from genetic defects in these genes. The project will involve the identification of these mutations and the biochemical characterization of the effects of these mutations in those who suffer from hereditary disorders.

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