Year: 2005
Type: dissertation
Abstract: Circadian rhythms are visible as daily oscillations in biochemical, \nphysiological, or behavioral processes. These rhythms are produced by an \nendogenous clock that maintains synchrony with the external environment \nthrough responses to external stimuli such as light or temperature. The clock, in \nturn, coordinates internal processes in a time-dependent fashion. Genetic and \nmolecular analysis of the filamentous fungus Neurospora crassa has \ndemonstrated that the products of the frequency (frq) and white-collar (wc-1 and \nwc-2) genes interact to form an interlocked feedback loop that lies at the heart of \nthe clock in this fungus. This feedback loop, termed the FRQ/WC oscillator, \nproduces a ~24h oscillation in frq mRNA, FRQ protein, and WC-1 protein. In \nturn, the FRQ/WC oscillator regulates rhythmic behavior and gene expression. \nThe goal of this dissertation is to understand how rhythmic outputs are regulated \nby the FRQ/WC oscillator in Neurospora. \nTo this end, we have taken a microarray approach to first determine the \nextent of clock-controlled gene expression in Neurospora. Here, we show that \ncircadian regulation of gene expression is widespread; 145 genes, representing \n20% of the genes we analyzed, are clock-controlled. We show that clockregulation \nis complex; clock-controlled genes peak at all phases of the circadian \ncycle. Furthermore, we demonstrate the clock regulates diverse biological \nprocesses, such as intermediary metabolism, translation, sexual development \nand asexual development. WC-1 is required for all light- and clock-regulated \ngene expression in Neurospora. We have shown that overexpression of WC-1 \nis sufficient to activate clock-controlled gene expression, but is not sufficient to \ninduce all light-regulated genes in Neurospora. This result indicates that cycling \nof WC-1 is sufficient to regulate rhythmic expression of a subset of clockcontrolled \ngenes. Conversely, a post-translational mechanism underlies WC-1 \nmediated light signal transduction in Neurospora. Finally, we have \ndemonstrated the Neurospora circadian system is comprised of mutually \ncoupled oscillators that interact to regulate output gene expression in the fungus.
Author: Zachary Lewis
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2734914524