Date of Award
Master of Science
Genetics, Development and Cell Biology
Genetics and Genomics
Autophagy was first isolated as a marker of starvation but has since then been identified and implicated in a variety of process both pathological or not. Lysosome density within a cell has long been used as a marker of activity of this pathway, as it represents the final location of degradation. Under normal conditions, lab strains of Drosophila melanogaster exhibit a low lysosome density considered to be universally observed. When challenged with starvation, this activity is expected to increase 2fold. We do not know if these characteristics are representative of natural populations, or the regulatory factors used to control the lysosome density within tissues.
By phenotyping 178 lines of the Drosophila Genetic Reference Panel for their lysosome density under resting and starved states, we were able to identify a previously uncharacterized variance in lysosome density phenotypes. Resting variation included multiple lines displaying an unusually dense lysosome phenotype previously not observed in lab strains. Furthermore, a Genome Wide Association Study performed on this data revealed that the gene sets associated with variance in resting and starved lysosome density were non-overlapping. Finally, RNA interference studies identified 4 previously non-implicated regulators of lysosome density; Myosin61F and corazonin as negative regulators and kin17 and elk as positive regulators.
This analysis presents a more complete picture of natural variance of lysosome density, and thus autophagy activation, as well as identifies novel regulators that may be responsible for controlling this observed variation.
Weeger, Axelle, "The Power of GWAS: Leveraging Genome Wide Association Studies to identify novel regulators of autophagy in Drosophila melanogaster" (2018). Graduate Theses and Dissertations. 16486.