Kári Ísleifsson
Autophagy is a conserved catabolic process found in all eukaryotic cells. ATG proteins regulate this process. Atg7 mediates the assembly of a double-membrane structure called an autophagosome (AP). The AP amasses damaged or unused cytosolic components and ultimately fuses with a lysosome, degrading them into materials that can then be reused within the cell. Autophagy appears to play an important role in the formation of cancers and can be thought of as a double-edged knife by hindering or enabling them to grow. Around 75% of disease-causing homologs can be found in the fruit fly Drosophila melanogaster, many oncogenes and Atg-genes included. This makes it a highly relevant model to study the effects of autophagy abrogation on cancer formation. We have successfully knocked out the endogenous Atg7 from the Drosophila genome and introduced two human ATG7 isoforms at the endogenous location. The effects of these isoforms on cancer development in the fruit fly are unknown and further studies give us insight into the pathways in which Atg7 is implicated. RasV12 benign tumors were driven in the eye discs (ey-GAL4 ) of Drosophila in autophagically-competent flies, Atg7 knockout flies and knockout flies with either human ATG7 isoform expressed. Eye irregularities were measured with the Fiji-plugin Flynotyper. Preliminary results indicate more disorder in eyes with hATG7 isoforms compared with control flies. These experiments allow us to further understand the pathways in which ATG7 is involved.
