Undergraduate Honors Theses

Thesis Defended

Spring 2017

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Dr. Tin Tin Su

Second Advisor

Dr. Rebecca Safran

Third Advisor

Dr. Christy Fillman

Abstract

Radiation resistance in human cancers represents a massive impediment for successful tumor treatment. The fruit fly Drosophila melanogaster is an excellent model for human radiation resistance because of its largely conserved apoptotic pathways and malleable genome. This thesis investigates the genetic regulatory mechanisms for bantam (ban), an anti-apoptotic microRNA. To first identify genes that interact with ban, a forward genetic screen was conducted. This screen looked for genes that yielded radiation dependent pupal lethality in a ban deficient background. From this screen the transcription factor, homothorax, was identified as displaying radiation dependent synthetic lethality with ban. To investigate the mechanism of synthetic lethality, larval wing imaginal disc were examined. It was found that hth deficiency does not modify apoptosis in ban deficient wing disc. Nor does hth seem to play a direct role in ban activation. However, the inhibition of hth was shown to result in aberrant cell migration and exacerbate wing disc overgrowths following irradiation. Additionally, preliminary data indicates that hth plays a role in the radioprotective Mahakali Effect. Specifically, a reduction in hth is correlated with a reduction in radiation protection from apoptotic cells. Though a direct mechanistic link between hth and ban has yet to be identified, a plausible mechanism of induced radiation sensitivity has emerged. It is speculated that some combination of cell death (from ban dysfunction) and aberrant recovery (from hth dysfunction) results in the synthetic lethality observed in ban/hth pupa following irradiation.

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