SBIR-STTR Award

We will use Proteinchipc Arrays with Surface-Enhanced-Laser-Desorption/Ionization Time-of-Flight Mass Spectrometry to obtain a large-scale profiling of the proteins whose brain expression is affected by sleep loss. ProteinChipc Arrays have been developed and marketed by Ciphergen Biosystems Inc., the "small business" in this proposal. The study will be conducted in fruit flies, rats and migratory sparrows, and sleep recordings and sleep deprivation experiments will be performed in the laboratory of Dr. Chiara Cirelli (University of Wisconsin - Madison), the "academic partner" in this proposal. Rats will be studied after acute and chronic sleep deprivation and sleep restriction, to mimic the different battlefield situations. Both wild-type flies, which show a cognitive deficit after sleep deprivation, and sleep-deprivation resistant mutant flies, which do not, will be studied. Both sparrows during the migratory season (when sustained sleep loss does not cause cognitive impairment) and during the nonmigratory season (when even acute sleep loss does) will be studied. The ability to profile gene expression in the brain of 3 different species, and the use of genetic and natural models of resilience to the negative effects of sleep loss will significantly increase the chance of identifying the best molecular markers of cognitive performance

We will use Proteinchip© Arrays/SELDI-TOF-MS (Ciphergen) to obtain a large-scale profiling of the brain proteins affected by sleep loss. Fruit flies, rats and sparrows will be sleep recorded and sleep deprived in the laboratory of Dr. Chiara Cirelli (UW–Madison). Rats will be studied after acute and chronic sleep deprivation and sleep restriction. Wild-type flies and sleep-deprivation resistant mutant flies will be studied. Sparrows will be studied when migrating (when they are not cognitively impaired) and during the non-migratory season (when they are, if sleep deprived). Phase I demonstrated that it is possible, using these animal models, to identify potential biomarkers of cognitive performance. Phase II will validate and extend these results by studying fractionated samples in a larger number of animals. We will use univariate/multivariate statistical analysis to discover multi-component biomarker patterns, and will identify up to 30 protein peaks. These findings will be instrumental 1) to identify molecular correlates of performance in individual sleep deprived subjects; 2) to search for biomarkers of sleep loss in peripheral tissues; 3) to design a diagnostic protein array that can distinguish sleep deprived subjects from controls; 4) to design a diagnostic protein array that can predict an individual’s performance under conditions of sleep deprivation.

Keywords:
Proteinchip Arrays, Seldi-Tof-Ms, Proteomic, Drosophila, Migratory Sleeplessness, Sleep Deprivation Resistant, Rat