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The Washington Research Foundation FellowshipAlicia Martin, Bioengineering - 2009-10 WRFF
Mentor: Celeste Berg, Genome Sciences Project Title: Developing Drosophila Melanogaster as a Model for Aminoglycoside Toxicity Abstract: Pseudomonas aeruginosa bacterial infections are a common problem in immune-deficient patients, such as burn victims, cancer patients, and cystic fibrosis patients. Treating these infections generally involves using an aminoglycosidic antibiotic, such as neomycin, which functions by blocking bacterial protein synthesis. Unfortunately, the range between effective treatment and toxicity is narrow. Patients treated long-term for P. aeruginosa infections often experience renal failure and deafness. The goal of this project is to develop the fruit fly, Drosophila melanogaster, as a model to understand the effects of neomycin treatment and to identify genes whose altered expression can help the fruit fly cope with the side effects of this drug. Knowledge gained from this type of study may facilitate development of a drug that targets P. aeruginosa infections with the same specificity but without the long-term side effects. Information from this study could also be used to ameliorate the side effects experienced by patients who are currently being treated with aminoglycosides. In order to develop this model, a dose-response curve of neomycin concentration to survivorship will be established. Then, I will analyze which tissues are affected by high doses of neomycin treatment by using molecular bioengineering techniques to insert an antibiotic resistance gene into flies. Using the GAL4- UAS system, a transgenic tool that allows Drosophila researchers to control when, where, and what is expressed, I will systematically drive this antibiotic resistance gene through various tissues in the flies. This will allow me to determine where the gene is essential for survival. Finally, I will perform a genetic screen using interference RNA to knock down expression of genes potentially involved in aiding aminoglycoside toxicity. Information gained from this screen will be useful for drug developers in the future, and may be used to develop diagnostics such as a microarray for determining the optimal route of therapy. |
Growing up with a brother with cystic fibrosis meant that genetics always played a profound role in my life. From a young age, I was fascinated by the field. I became involved in the Department of Bioengineering during my sophomore year because I was interested in developing the engineering skills required to design solutions to biomedical problems. As I progressed through my major, I decided to pursue a position in a lab in the Department of Genome Sciences so that I could more directly research the topics that interest me. I am fortunate to be working under Dr. Celeste Berg, who has been extremely supportive of my research and has helped me come up with independent research projects. During my junior year, I received support from the Howard Hughes Medical Institute to study tubulogenesis, the formation of tubes from flat epithelial sheets of cells, at the genetic level. This process occurs during the development of essential organs, such as the heart, lungs, gut, kidneys, and neural tube. To fulfill the requirements of my senior capstone project, I am switching projects and am researching antibiotic toxicity. I am grateful to be receiving enabling support of the WRFF and Ronald E. McNair Program for this project. Having found my niche in research, I am applying to graduate school with hopes of obtaining my PhD in biomedical sciences, specifically in genetics or molecular, cell, and developmental biology.