Alpha Omega Alpha Honor Medical Society

2010 Research Abstract

A Drosophila Model for Adenovirus E1A Oncoprotein Pathogenesis

Investigator: Christina Brown, Department of Biomedical Sciences, Florida State University College of Medicine
Mentor: Timothy Megraw, Department of Biomedical Sciences, Florida State University College of Medicine

The DNA tumor viruses share in common the ability to transform vertebrate cells through the action of virus-encoded tumor oncoproteins that interfere with normal cell physiology. We created a genetic model to dissect the pathogenesis and tumorigenesis produced by the DNA tumor virus Adenovirus-5 (Ad-5). We used the GAL-4 system to control the tissue-specific expression of the Ad-5 oncoprotein E1A in Drosophila melanogaster during development. Expression of E1A in the eye resulted in a 'glassy' eye phenotype that is amenable to genetic modifier screens. This stock was then used to identify individual gene mutations that modify (suppress or enhance) the eye phenotype, allowing the discovery of potential interacting proteins and elucidation of the pathways involved in cancer and in other aspects of E1A pathogenesis. Screening of 400 hairpin RNAi "TRiP" lines, and 200 deficiency mutations on the second chromosome has yielded fifteen potential genes that interact with the E1A pathway. Interactions with mutations in genes encoding homologs of known effectors of E1A pathogenesis in mammals, along with the novel genes that were found to enhance the E1A phenotype in this study are reported here. In addition, mutations in the domains that elicit known E1A functions are under investigation. Cytology and biochemistry will be implemented to elucidate how these genes promote or suppress pathogenesis of E1A. This Drosophila model for E1A pathogenesis offers a promising way for efficient screening of genes that interact in the E1A pathway, allowing further investigation of how the DNA tumor viruses lead to tumor growth and how this growth may be controlled clinically.

Updated on June 8, 2011.

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