Research Topics
Department of Chemistry
Ph.D. (1978) University of Wisconsin
Research Topics
Research Interests
Biochemical regulation involves complicated feedback among enzyme and substrates. The consumption of a substrate by one enzyme may alter the rate at which another enzyme metabolizes a different substrate. If in turn that different substrate can regulate the behavior of the first enzyme, a phase-delay oscillation is possible, and, under many circumstances, likely. The dynamics of chemical oscillation and of biochemical regulation and circadian rhythms are theoretically quite similar. Our research explores the chemical and biochemical dynamics of oscillatory reactions.
The current focus of study is the peroxidases. Given a constant feed of oxygen and NADH, the concentration of oxygen in solution can spontaneously oscillate. Qualitatively, one builds up oxygen concentration until a burst of free radicals generated by the enzyme and NADH depletes the oxygen, after which the cycle repeats. Recently, we have succeeded in devising a qualitatively and quantitatively useful model for plant peroxidase activity. Our emphasis is shifting to mammalian perioxidases. Our group seeks to thoroughly understand the rate constants and speciation involved in the reaction. From such understanding, there are three primary consequences:
1. Quantitative predictions of oscillatory patterns for the peroxidase system can be made, so that reaction conditions necessary to generate any desired periodic or aperiodic pattern can be calculated.
2. New families of biochemical oscillators can be devised.
3. Coupled oscillators can be rigorously studied, and the change, from reaction dynamics primarily controlled by kinetics of a specific system to dynamics controlled by the interaction of coupled systems, elucidated.
The myeloperoxidase system in mammalian neutrophils and the metabolic network in peroxisomes are our current specific focus.
Sensors developed as in conjunction with this work are being applied to studies of the role of oxidative stress in noise-induced hearing loss.
Key Words Bioengineering, Fermentation, Biomass Conversion, Biodegradation,
Protein Purification and Characterization, Biocatalytic Conversions
Current Research Funding
NSF, Research Corp., Deafness Research Foundation