Targeting cancer through the gene that prevents tumor growth

Learning how to control oncogenes has always been a goal of cancer therapeutics, but it is very difficult to develop effective drugs against them. My thesis focuses on manipulating microRNAs(miRNA) to silence specific genes in the Notch pathway. This pathway is responsible for cell-cell communication necessary for cell division and development. It has been conserved from flies to humans and it is mutated in many human cancers. When this pathway is over-active, it causes the growth of tumors because cell division isn't regulated. Using Drosophila melanogaster as a model system, we can synthesize these results by using miRNAs to knock out genes in the Notch pathway.

miRNAs are small strands of RNA that have the ability to inhibit gene expression, therefore having tumor suppressive potential. They bind to target messenger-RNA(mRNA) to create a double stranded RNA molecule. This molecule can no longer be "read" by the ribosome, which means the mRNA does not get translated into its gene product.

Preliminary screens in the Markstein lab suggest that 9 miRNAs in Drosophila appear to increase stem cell formation, which means they are silence genes in the Notch pathway. I will over express these miRNAs in two biological assays, the gut and the wings. I will dissect these flies and analyze their stem cells and wing development to determine if they are in fact interrupting Notch signaling. Some miRNAs might produce the Notch phenotype in the gut, but not the wing. This is important because it would suggest that Notch signaling differs between these two systems, or it could lead to the discovery of new genes in the pathway.

After conducting this research, the Markstein lab will use bioinformatics and sequence analysis to determine the exact target of each miRNA and identify shared targets. Studying miRNAs and determining their direct targets can help us control the effects they have on gene expression and allow us to potentially use them as cancer therapeutics.