The NIH funded research in the Lynn group focuses on development and utilization of mass spectrometry to address environmental and biological problems. Projects range from studies of protein transcription and development of ultra-sensitive methods to monitor environmental contaminants, to changes (function and quantity) in mitochondrial proteins brought about by the progression of Alzheimer's disease (AD) and the identification of biomarkers of human disease. We use a variety of mass spectrometers and sample introduction techniques to pursue these objectives including ion trap, time-of-flight, magnetic sector, and ion cyclotron resonance spectrometers equipped with GC, HPLC and MALDI sample introduction/ionization techniques.
The REU undergraduate project will utilize GC/MS and tandem mass spectrometry to develop methods for quantification of biomarkers of lipid peroxidation associated with AD. We are specifically interested in developing methods to quantify neuroprostanes. Neuroprostanes
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| result from the nonenzymatic peroxidation of docosahexaenoic acid, an unsaturated fatty acid highly concentrated in the brain. Neuroprostanes are highly unsaturated, prostane ring containing, diol carboxylic acids. These peroxidation products are thermally unstable, difficult to isolate, and difficult to analyze by GC/MS. Previous methods to analyze neuroprostanes have utilized electron capturing derivatization and negative ion chemical ionization (NICI). While extremely sensitive, NICI is not very robust resulting in large measurement errors. We propose an alternative technique that utilizes traditional electron impact ionization of derivatives designed to enhance tandem mass spectral analysis. Initial screening of derivatives has generated several candidates with appropriate characteristics. The REU student will evaluate these candidate derivatives on model neuroprostanes and develop a sensitive and specific GC/tandem mass spectrometry method to quantify these compounds. The REU student will gain experience in quantitative analytical techniques, micro-scale derivatization, gas chromatography, tandem mass spectrometry on ion trap mass spectrometers, and method validation. This project will be interesting to both biologically oriented students as well as analytical/ instrumental oriented students. A 10 week effort in this area should easily produce publishable results. |
