Proper regulation of sleep and metabolism are critical to the survival of all organisms. In humans, dysregulation of sleep is linked to metabolic syndrome, including hypertension, hyperglycemia and hyperlipidemia. However, the mechanisms regulating interactions between sleep and metabolism are poorly understood. Although the fruit fly, Drosophila melanogaster, bears little anatomical resemblance to humans, it shares similar genetics essential in understanding normal development and disease in humans. From humans to flies, many disease-related genes and pathways are highly conserved, rendering the fruit fly ideal to understanding the interactions between sleep and metabolism. Therefore, using the fruit fly provides a framework for understanding how genes function between sleep and metabolism. During starvation, both humans and rats reduce their sleep. Similarly, previous studies have shown that fruit flies also suppress sleep to forage for food, further showing that sleep and metabolism are intricately tied to one another and that they are highly conserved across species. To further explore the interactions between sleep and metabolism, I have conducted multiple genetic screens to identify novel regulators of sleep-metabolism interactions. These experiments led to the identification of the mRNA binding protein translin (trsn) as being required for starvation-induced sleep suppression. A second screen that targeted metabolic genes from a genome-wide association study identified the ion channel accessory protein uncoordinated 79 (unc79) as a critical regulator of both sleep duration and starvation resistance. The genes function in different regions of the brain and suggest complex neural circuitry is likely to underlie regulation of sleep metabolism interactions. Taken together, a mechanistic understanding of how different genes function to regulate sleep in flies will further our understanding of how sleep and metabolism is regulated in humans. / Includes bibliography. / Dissertation (PhD)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

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Aldehyde oxidase has been partially purified from Oregon-R-C and tuh(ASU) strains of Drosophila melanogaster using an affinity technique. The two enzymes were subjected to a partial kinetic analysis and found to be very similar to one another. This indicated the problem of elevated aldehyde oxidase activity in tuh(ASU) at key developmental stages (Kuhn and Cunningham, 1976) is due to an abnormal regulation. A comparative isozyme study through the developmental stages showed no major differences between the enzymes indirectly supporting the idea of an abnormal regulation. A comparison of tuh(ASU) with four wild-type strains indicated it may be a fourth allozyme of aldehyde oxidase.

The genetic factors controlling Mixed Function Oxidase (MFO) Activity and malathion resistance was studied in the larva and the adult of a malathion resistant strain of Drosophila melanogaster. In addition, the developmental expression and tissue localization of high MFO activity was characterized in the larva and the adult. Microsomal extracts from a strain with a resistant second chromosome were found to have increased amounts of protein with a relative molecular mass of 52 kD, while a strain with a resistant third chromosome was found to have increased amounts of proteins with relative molecular masses of 51 and 55 kD in the microsomal extract. MFO activity associated with a strain with a resistant second chromosome was found to be most concentrated in the intestine and abdominal wall of the imago, while found primarily in the malpigian tubules and the fat body of the larva. The mapping of genes on the second chromosome associated with larval resistance to malathion suggested two loci, a major resistance gene at 2-64 cM and a second minor resistance gene. The mapping of genes on the second chromosome associated with adult resistance again suggested two loci, one at 2-64 cM and a second just to the left of the marker black (48.5 cM). The mapping of genes on the second chromosome associated with high PNA demethylase activity (an MFO activity) in the adult suggested a locus at 2-64 cM and a second between 54.5 and 60.0 cM. The locus at 2-64 cM and a third locus between 48.5 and 51 cM was found to be associated with high 7-EC hydroxylase activity ( a second MFO activity) in the adult. / Thesis / Master of Science (MS)

The length of eukaryotic chromosomes is many times longer than the nucleus diameter in most cells; thus, their confinement depends on adopting highly folded configurations. Remarkably, these configurations are non-random and may be important for gene expression and regulation. Thus, genome sequences must be understood in the context of their 3D organization which critically influences the flow of information. The effort to understand this added complexity now encompasses an entire field of chromosome biology and is reshaping the traditional concept of the central dogma. Although little is known about the principles which govern chromosome folding and influence gene regulation, the nuclear envelope is expected to play a significant role since it serves as the physical boundary preventing chromosome from freely diffusing in the cell cytosol. Moreover, experiments suggest that the nuclear envelope engages chromosomes actively by anchoring specific loci and limiting their range of motion. The broad goal of the research presented in this dissertation is to advance our understanding of 3D genome organization with an emphasis on determining the role of the nuclear envelope. / Ph. D.

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Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 117-134).