SUSAN ROBERTS LAB

Plant Biology Rotation Project

Plant cell culture technology has shown promise for the production of valuable pharmaceuticals that cannot be obtained in sufficient yield by natural production or are too complicated for chemical synthesis. The current lack of knowledge about the factors that control plant cellular metabolism severely limits the regular use of plant cell culture technology commercially, due to low product accumulation rates and inability to maintain high productivity levels. Paclitaxel is a potent anti-cancer agent, approved by the FDA for the treatment of a variety of cancers and is in part supplied via plant cell culture. Our laboratory has been involved in paclitaxel production from plant cell culture for the past seven years. We have recently established collaborations with the Walker and Normanly laboratories to apply molecular approaches to understanding regulation of paclitaxel metabolism. As part of this collaboration, we are identifying genes that control paclitaxel accumulation. These genes may be involved not only in biosynthesis, but also transcriptional regulation and degradation. This rotation project will specifically investigate paclitaxel degradation in plant cell cultures. We have preliminary data suggesting that paclitaxel is degraded to structurally similar compounds during the cell culture process, but are unclear as to the mechanism of degradation. This project involves investigation of paclitaxel degradation through both radiolabeled studies (e.g., spiking cultures with radiolabeled paclitaxel and profiling the metabolites that are produced over time) and assaying the function of putative degradative genes suggested from a systems-wide transcript profiling analysis. Project goals will be specifically designed based on student input and interest. A student who decides to undertake this project will gain experience in plant cell culture, HPLC analysis for detection and quantification of paclitaxel and related compounds, and design and execution of radiolabeled experiments. The student will also partake in biweekly group meetings held in conjunction with the Walker and Normanly laboratories.