PhD Candidate Research Assistant University of Kentucky Lexington, Kentucky
Body of Abstract: A widely known treatment for leukemia, chemotherapy, utilizes two compounds vinblastine and vincristine. Vinblastine and vincristine are specialized metabolites synthesized for defense via the Monoterpene Indole Alkaloid (MIA) biosynthesis pathway in the subtropical plant Catharanthus roseus, more commonly known as Madagascar Periwinkle. There are two problems, these compounds are produced in low yield and due to structural complexity of these compounds prevents manufacturing as a viable option. What researchers have found was that the pathway is a complex network of enzymatic genes and transcription factors forming a regulation network of feedback loops controlling production.
Mediators serve as a bridge between TFs and Pol II to activate transcription on promoters of target genes. One such mediator is MED25, which is involved in JA-signaling. The MIA biosynthesis pathway that produces vincristine and vinblastine, is induced via the JA-signaling pathway. Therefore, due to sequence and domain structure similarity we hypothesize that MED25 serves a functional role in a novel biosynthesis pathway exclusive to Catharanthus roseus. Through our experimental approach we were able to demonstrate protein-protein interactions between MED25 and key MIA pathway genes using Yeast-Two Hybrid. We found that when we overexpressed or repressed MED25 in hairy roots, dynamic variations in expression of key MIA pathway genes occurred. And that when MED25 is repressed the plant becomes desensitized to MeJA. Identifying a novel function of MED25 in the MIA biosynthesis pathway will help fill in informational gaps, leading us closer to improving the production efficiency of these vital chemotherapants.