Biology

Title

A Functional Analysis of Drosophila PLCgamma and the Screening for a Novel Inhibitor

Date of Award

6-2017

Degree Type

Thesis

Degree Name

Master of Science in Biochemistry & Molecular Biology

Department

Biology

Chief Instructor

Justin Thackeray

Second Reader

Denis Larochelle

Third Reader

Deborah Robertson

Abstract

The epidermal growth factor receptor, EGFR, pathway is a highly conserved and complicated pathway required for cell growth, proliferation, migration, and proper regulation of the pathway is required for normal development (reviewed by Fischer et al., 2003). Due to the pathways role in development, the EGFR pathway is often implicated with various diseases including cancer. The EGFR pathway is regulated by various proteins including by PLCgamma which works to regulate the pathway by promoting motility, adhesion, and differentiation (Murillo-Maldonado et al., 2011; Butchar et al., 2012; Shepard et al., 2006). Because of the role PLCgamma plays in cell proliferation, it is being studied as a possible anti-carcinogenic drug target. The purpose of this study was to identify a possible inhibitor of PLCgamma in vivo in Drosophila. I started with a diversity set of approximately 1600 drugs obtained from the National Cancer Institute and after three drug screens targeting various regulatory proteins of the EGFR pathway I was able to identify one drug, 4788 E3 as a possible inhibitory drug for PLCgamma. In order to learn more about the structure and function of PLCgamma, which is encoded by small wing, sl, I also examined the pleckstrin homology or PH domains present in PLCgamma. I examined Drosophila lines carrying mutations in both the PH-C and PH-N domains in an sl9 background and through eye sectioning was able to determine the effect the mutated domains played on PLCgamma function. I found that the two domains work separately from one another performing different functions to ensure proper PLCgamma function, predicting complementation.

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