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An Rnai Screen to Identify Components of a Polyamine Transport System

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An Rnai Screen to Identify Components of a Polyamine Transport System University of Central Florida STARS Honors Undergraduate Theses UCF Theses and Dissertations 2017 An RNAi Screen to Identify Components of a Polyamine Transport System Adam J. Foley University of Central Florida Part of the Animals Commons, Biology Commons, Cell and Developmental Biology Commons, Genetics and Genomics Commons, Medical Cell Biology Commons, Medical Genetics Commons, Medical Molecular Biology Commons, and the Oncology Commons Find similar works at: https://stars.library.ucf.edu/honorstheses University of Central Florida Libraries http://library.ucf.edu This Open Access is brought to you for free and open access by the UCF Theses and Dissertations at STARS. It has been accepted for inclusion in Honors Undergraduate Theses by an authorized administrator of STARS. For more information, please contact [email protected]. Recommended Citation Foley, Adam J., "An RNAi Screen to Identify Components of a Polyamine Transport System" (2017). Honors Undergraduate Theses. 187. https://stars.library.ucf.edu/honorstheses/187 AN RNAi SCREEN TO IDENTIFY COMPONENTS OF A POLYAMINE TRANSPORT SYSTEM by ADAM J. FOLEY A thesis submitted in partial fulfillment of the requirements for the Honors in the Major Program in Biology in the College of Sciences and in The Burnett Honors College at the University of Central Florida Orlando, Florida Spring Term 2017 Thesis Chair: Dr. Laurence von Kalm Abstract: Polyamines, specifically putrescine, spermidine, and spermine, are small cationic molecules found in all organisms. Cells can biosynthetically make these molecules, or alternatively, they can be transported from the extracellular environment. Malignant cells have been shown to require relatively high amounts of polyamines. There is a chemotherapeutic agent used to block the biosynthesis of polyamines. However, malignant cells can circumvent DFMO therapy by activating their transport system. A potential solution is to simultaneously block biosynthesis and transport of polyamines. Additionally, little is known about the polyamine transport system in higher eukaryotes. This thesis aims to add to the basic biological understanding of the polyamine transport system, as well as contribute to our understanding of the way in which malignant cells are able to sustain rapid growth. This was done by screening six candidate genes believed to be involved in the polyamine transport system. These six genes were identified using various bioinformatics databases. They were screened using RNAi to knock down each gene of interest and by using an assay developed in our lab. One of the genes, RabX6, may play a possible role in the transport of putrescine. ii Acknowledgments: I would like to sincerely thank everyone who made my thesis possible. Thank you to all of the graduate students (Corey Seavey, David Brown, Nicole Barnette, and Michael Haney) for integrating me into the lab, helping me with my project, and for teaching me more than I ever thought I would know about Drosophila. Also, thank you to the undergraduate students in the lab for assisting me with my project when needed. Dr. Otto Phantiel IV and Dr. Kenneth Fedorka, I thank both of you for being on my committee, and for your guidance throughout this process. Dr. Kenneth Teter, thank you for agreeing to be on my committee, even though there had to be some last minute changes. To my thesis chair, Dr. Laurence von Kalm, I greatly appreciate your mentorship throughout this project. I have learned so much over the past two years, and I thank you for that. Lastly, I would like to thank my friends and family who have supported me during my time here at the University of Central Florida. I could not have done it without you all. iii Table of Contents: Introduction: ................................................................................................................................................. 1 Methods: ....................................................................................................................................................... 5 Identifying and Prioritizing Candidates: .................................................................................................... 5 STRING-10 ............................................................................................................................................. 5 GeneCards ............................................................................................................................................. 8 Flybase/modMine ................................................................................................................................. 9 Knockdown of Genes: ............................................................................................................................. 11 Polyamine Transport Assay: .................................................................................................................... 12 Results: ........................................................................................................................................................ 18 Slip1: ........................................................................................................................................................ 18 CG31998: ................................................................................................................................................. 20 Cals: ......................................................................................................................................................... 21 Exd: .......................................................................................................................................................... 23 Poxn: ....................................................................................................................................................... 24 RabX6: ..................................................................................................................................................... 26 Discussion: .................................................................................................................................................. 28 Conclusion: .................................................................................................................................................. 30 Appendix A: Complete List of Transcription Factors ................................................................................... 31 Appendix B: 262 Genes from Cluster 34 ..................................................................................................... 35 Appendix C: Prioritized List of 28 Potential Genes to Study ....................................................................... 38 Appendix D: Finalized List of 16 High Priority Genes .................................................................................. 40 References: ................................................................................................................................................. 42 iv List of Figures Figure 1: Biosynthesis of polyamines. ........................................................................................................... 2 Figure 2: Interaction map with predicted functional partners of CG32000 ................................................. 7 Figure 3: Transcription factor binding site map for the human gene ATP13a3............................................ 9 Figure 4: Illustration showing RNAi in a Drosophila cross. ......................................................................... 12 Figure 5: Results from an ActinGAL4 x CG32000 RNAi cross. ..................................................................... 17 Figure 6: Graph showing the percent viability of RNAi expressing flies that eclosed across 6 replicates for Slip1. ............................................................................................................................................................ 19 Figure 7: Graph showing the percent viability of RNAi expressing flies that eclosed across 3 replicates for CG31998. ..................................................................................................................................................... 20 Figure 8: Graph showing the percent viability of RNAi expressing flies that eclosed across 6 replicates for Cals. ............................................................................................................................................................. 22 Figure 9: Graph showing the percent viability of RNAi expressing flies that eclosed across 3 replicates for Exd. .............................................................................................................................................................. 23 Figure 10: Graph showing the percent viability of RNAi expressing flies that eclosed across 3 replicates for Poxn. ...................................................................................................................................................... 25 Figure 11: Percent viability of RabX6 RNAi expressing flies across all 8 treatments. ................................. 27 Figure 12: Entire list initially generated when identifying transcription factors of ATP13a3. .................... 32 Figure 13: Entire list initially generated when identifying transcription factors of ATP13a3 (continued from previous page). ..................................................................................................................................
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