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The Scheeline Group's current research is in some way ultimately linked to oxidative stress. As a general definition, oxidative stress is the damage caused by reactive oxygen species (ROS) to cells, proteins, DNA, and membranes. ROS include a large number of free radicals such as the hydroxyl radical and superoxide anion. Oxidative stress caused by these two particular free radicals is believed to be linked to many neurological disorders and hearing loss. It is thus advantageous to have instrumentation to monitor these species both in vitro and in vivo. Limitations in current instrumentation and the inherent characteristics of free radicals, such as the relatively short lifetime of the hydroxyl radical, provide a unique problem and platform for analytical chemical research. Thus, one of the overall goals for the Scheeline Group is to invent analytical techniques and instrumentation to gain a greater understanding of the cellular pathways and how these pathways are affected by oxidative stress.
Many enzymes are present in only small qunatities, so studying their kinetics is difficult with conventional apparatus. NASA's Jet Propulsion Laboratory has developed apparatus for looking at fluid mechanics in microliter drops. Combining the JPL drop apparatus with our ideas about electro-osmotic transport, we can design apparatus for study of enzyme kinetics where only an attomole of enzyme would be needed for determination of rate constants and only picomoles would be required for full characterization of kinetic behavior. Also may be of interest for pulse radiolysis experiments.
Three percent of the world's population is plagued with noised induced hearing loss (NIHL). With life spans expanding due to advances in cardiac care and cancer research, this number is likely to increase in the coming decades. Being able to understand the cause is key to finding a remedy or devising pharmaceutical preventatives. A correlation between oxidative stress and NIHL has already been found. To monitor the reactive oxygen species (ROS) in situ requires a unique perometric electrode, small enough to be unobtrusive for use in animal studies. Once this new electrode is fabricated, further investigations into the temporal course of ROS generation during noise exposure, without sacrificing the test animal (Mongolian gerbil), can be made.
An important component of the immune system is a complex network of enzymes and cells whose primary function is fighting pathogens which may enter the organism. Included in this arsenal are neutrophils, a type of phagocyte, which compartmentalize bacteria inside the cell and then pummel them with cytotoxic compounds. A primary method of attack is through oxidative species, many of which are derived through reactions involving myeloperoxidase (MPO). NADPH Oxidase, bound to the interior wall of the phagosome, produces hydrogen peroxide through an oscillatory mechanism. While it is clear that the interaction between MPO and hydrogen peroxide is necessary to initiate a cascade of possible reactions, the scope of those reactions and products is vast (as can be seen from the figure below) and far from being completely understood.
The focus of this group's research is to better understand these reaction mechanisms and their non-steady-state reaction dynamics. It continues to be unclear whether the oxidative species produced by the H2O2-MPO interaction are the direct cause of pathogen attack or if other proteins acting in response to the oxidative stress are the cause of pathogen demise.
Chaos is deterministic behavior that occurs when multiple trajectories have identical or nearly identical energy and low barriers for switching among orbits. Life is characterized by being adaptable, that is, choosing among alternatives, with large changes in outcomes stemming from small changes in instantaneous behavior (turn left and get run over by a car, turn right and purchase ice cream from a vendor. Energy difference: 0. Quality of life difference: infinite). Life is also characterized by learning; among many similar behaviors, those found to be most effective are typically repeated. Adaptation to the Edge of Chaos is a hypothesis (championed by Prof. Alfred Hubler, UIUC Department of Physics) that chaotic processes with nominal parameters positioning them between stability and chaos will in fact spend most of their time in periodic or stable regimes, and then briefly explore chaotic space before returning to stability. We are testing this hypothesis using reactions capable of chaotic oscillation (peroxidase-oxidase, Belousov-Zhabotinskii).
In the course of our work on the peroxidase-oxidase oscillator, it became clear the dimer of NAD free radical was an important, transient species occurring only during free radical burst. This naturally raised the question of what in vivo role NAD2 might play. Through a combination of chemical and biological measurements (the latter in collaboration with UIUC Prof. of Crop Sciences Michael Plewa), we are seeking evidence of any unique role the dimer may play in sensing, communicating, or effecting oxidative stress.
This group was originally focused on study of atomic emission spectroscopy of solid samples. From 1979-1995, much of our work focused on spark and theta pinch discharges. We continued this work in a collaboration with J. O. L. Wendt (University of Arizona) and others examining drop dynamics in thermal reactors used for processing metal-containing liquid wastes. We more recently have changed to a focus on low-resolution spectroscopy of biological molecules.