Perturbations to the physiology or impairments in the formation of synapses within the cochlea, specifically the ribbon synapses, result in decreased sensitivity to auditory stimuli. In example, prolonged exposure to moderately intense auditory stimuli, like power tools, can result in the swelling of nerve terminals, retraction of the postsynaptic membrane,...
Compromised protein homeostasis underlies accumulation of plaques and tangles in Alzheimer’s disease (AD); however, little is known about the early mechanisms that contribute to this process. To objectively assess protein turnover at early stages of amyloid beta (Aβ) proteotoxicity, we used dynamic metabolic labeling with stable isotopes followed by proteomic...
Epigenetics is the study of chromatin-based events that regulate gene expression without the change of DNA sequence, including DNA methylation, histone modification and chromatin remodeling. Epigenetic regulators are encoded to modify chromatin in a highly regulated and dynamic manner. A growing number of studies have suggested the dysregulation of epigenetic...
What follows is a strictly post-genomic dissertation. Over the past five years, I have strived to leave the nucleus behind, and even the endoplasmic reticulum and golgi apparatus. The human genome was sequenced over 15 years before the submission of this document, and the world changed somewhat less than anticipated—besides...
Traditional bottom-up mass spectrometry-based proteomics relies on the use of an enzyme, often trypsin, to generate small peptides (typically < 25 amino acids long). In top-down proteomics, proteins remain intact and are directly measured within the mass spectrometer. This technique, while inherently simpler than bottom-up proteomics, generates data which must...