Polyamines are small positively charged molecules that control major vital cellular processes including cell growth and proliferation, gene expression, protein production and cell death. Cells can obtain polyamines by making them (biosynthesis) or bringing them into the cell from the outside (transport). Cancer cells require high levels of polyamines to sustain their rapid growth, and depletion of polyamines slows the growth of malignant cells. An FDA approved drug, difluoromethylornithine (DFMO), blocks biosynthesis but is often ineffective because tumor cells respond by increasing transport of polyamines. Thus, a dual therapy that simultaneously targets polyamine biosynthesis and transport is needed. The mechanism of polyamine transport is poorly understood in multicellular eukaryotes and our laboratory focuses on the identification of genes involved in polyamine transport in Drosophila. Our previous work has shown that the transport of polyamines in Drosophila has many similarities to mammalian transport systems, suggesting that Drosophila may be a good model to investigate polyamine transport in mammals. To test this hypothesis, I utilized a novel genetic assay in Drosophila in an attempt to identify positive and negative regulators of polyamine transport. In addition to validating the assay with a gene known to positively regulate polyamine transport, I attempt for the first time to use a strategy designed to identify negative regulators of transport. The major findings are that the Drosophila genes dSLC12A8 and slimfast, which encode cationic amino acid transporters, are required but not essential for polyamine transport. Ultimately, as more components of the polyamine transport system are identified it will be possible to develop drugs that selectively interfere with polyamine transport in mammals and use them in combination therapy with DFMO.
von Kalm, Laurence
Bachelor of Science (B.S.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Millington, Victoria A., "Using Genetics in a Model Organism to Understand Polyamine Transport" (2021). Honors Undergraduate Theses. 925.