Senior physics major Danielle Desa, and junior physics major Christina Miller have been invited to give talks at the 2015 Conference for Undergraduate Women in Physical Sciences. The conference will be held Thursday, Oct. 15 - Saturday, Oct. 17, 2015 at the University of Nebraska at Lincoln.
Christina Miller, 12:10 p.m. on Thursday October 15th, Applying nonlinear optics to monitor changes in cellular metabolism with the onset and progression of disease
Abstract: Every year there are about 1.6 million new cases of cancer and more than 500,000 cancer related deaths just in the United States. Like other diseases, the key to an effective treatment is early detection and monitoring its progression. To this end, we have used intensity-, time-, and wavelength-resolved multiphoton microscopy to measure changes in cellular metabolism. By analyzing the fluorescence emission of metabolic coenzymes such as the reduced form of nicotinamide adenine dinucleotide (NADH), variations in the metabolic-related microenvironment can be quantified. Fluorescence lifetime imaging (FLIM) was used to quantify metabolic changes due to overexpression of growth factors associated with more aggressive cancers. To further extend this to clinical approaches, this optical profiling technique has also been adapted to mouse skin and to identify changes in fluorescent metabolic signals.
Danielle Desa, 4:40 p.m. on Saturday Oct. 17th, OTOTOXIC AMINOGLYCOSIDES INCREASE REACTIVE OXYGEN SPECIES FORMATION AND DECREASE ENDOGENOUS ANTIOXIDANT LEVELS IN COCHLEAR CELLS
Abstract: Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain the most widely used class of antibiotics in the world. Cell-damaging reactive oxygen species (ROS) form during AG ototoxicity but the source of these free radicals is poorly understood. During normal mitochondrial metabolism low levels of ROS, primarily superoxide, are produced at complexes I and III in the electron transport chain. These levels can increase when mitochondrial dysfunction occurs.
To determine if acute AG exposure causes changes in mitochondrial ROS production, superoxide (O2.-) and hydrogen peroxide (H2O2) ROS were measured using MitoSox Red and Dihydrorhodamine 123, respectively. Site-specific ROS production was assessed with the complex-I inhibitor Rotenone and the complex-III inhibitors Antimycin A and Myxothiazol. As expected, each complex inhibitor significantly increased mitochondrial O2.-, indicated by an increase in MitoSox Red fluorescence intensity. Exposure to a representative AG, gentamicin (GM, 300 mg/ml), did not significantly increase O2.- production, but did significantly increase H2O2 levels within one hour of exposure. At the same time point, GM significantly increased manganese superoxide dismutase (mnSOD) levels and significantly decreased copper/zinc superoxide dismutase (cuznSOD) in cochlear sensory cells. This suggests 1) a rapid conversion of highly reactive O2.- to H2O2 during the acute stage of ototoxic antibiotic exposure and 2) that the endogenous antioxidant system is significantly altered by ototoxic antibiotics. This project provides a base for understanding the underlying mechanisms of mitochondrial ROS production in cochlear cells during exposures to ototoxic antibiotics, which is critical for developing hearing loss treatment and prevention strategies.