Investigating the Defense-Related Responses of Plants

Carolyn Lee-Parsons and Erin Cram

ChE/COS Associate Professor Carolyn Lee-Parsons and BioE Affiliated Faculty member Erin Cram were awarded an $800K NSF grant for creating “A Novel CRISPR SynBio Tool for Investigating and Reprogramming the Regulation of Alkaloid Biosynthesis in Catharanthus roseus.”

Changing the Programming of Plant Cells to Produce Anti-Cancer Compounds

Vincristine is a chemotherapy drug used to combat childhood cancers such as leukemia, lymphoma, and brain tumors. This life-saving compound, however, is in low supply, forcing doctors to ration doses and preventing children who need this drug from receiving it.

As part of a three year $800K NSF grant, titled, “A Novel CRISPR SynBio Tool for Investigating and Reprogramming the Regulation of Alkaloid Biosynthesis in Catharanthus roseus,” Carolyn Lee-Parsons, associate professor of chemical engineering, and her collaborator, Erin Cram, professor of biology, are studying the Catharanthus roseus plant. The plant is the only source of the anti-cancer compounds vinblastine and vincristine, and through their research they hope to increase the production of these critical compounds. “The reason why I studied this plant is because the compounds that it produces are so critical for the treatment of cancer and there’s no other substitute,” says Lee-Parsons.

Catharanthus roseus is commonly referred to as the Madagascar periwinkle, and like any plant, it uses carbon dioxide for photosynthesis, which ultimately enables plant growth and the production of specialized compounds such as UV protectants and insect repellants that are valuable to its survival. However, there are limited amounts of sugars available, thus the plants need to wisely decide how to use this.  In this way, plants are adaptable and can allocate the available sugars based on what is going on in their environment.

Lee-Parsons and her team are growing tissue cultures derived from the Madagascar periwinkle in a controlled carbon-rich environment so that the cultures do not need to photosynthesize. This allows the plant tissues to produce more of the anti-cancer compounds.

One of the challenges of this project is that the plant doesn’t produce a lot of vinblastine and vincristine because the plant has ways of turning off production once its production has been turned on. Therefore, one of Lee-Parsons’ goals in this project is to understand how the plant regulates production so that she can develop a strategy to increase it. She is also addressing this limitation by developing a synthetic biology tool which will allow her team to reprogram the DNA within the cells of the plant to instruct it to produce more anti-cancer compounds. Essentially, Lee-Parsons is altering the instructions for how the plant uses its resources. She hopes that this toolset will be useful to other plant scientists so that they can also reprogram their pathway or increase production for their pathway.

“Ultimately we want to meet our research vision, which is to produce these compounds through engineered plant cultures that will produce enough of this critical drug so that all patients who need it can have it—right now that isn’t the case. Some kids are not receiving the treatment they need [because] there’s not enough of the drug,” Lee-Parsons explains.

Lee-Parson’s interest in medicinal plants came about through a combination of her childhood interest in math and science, as well as the influence of the use of traditional medicine in her Chinese culture leading her to study chemical engineering and the use of plants to produce medicine. Regarding this specific project, Lee-Parsons says, “It’s been a journey for me of using my chemical engineering background to develop the bioprocess as well as to engineer the cell.” She began this project by developing a bioprocess to produce and extract more anti-cancer compounds from plant cultures, and finally she moved on to reprogramming the cell itself to produce more compounds.

This journey is far from over, but Lee-Parsons is working toward solving the shortage of this chemotherapy drug so that children battling cancer have the treatment they need. Lee-Parsons shares, “The kind of work that people do as scientists and engineers is really important.”

Grant Source: NSF


Related Faculty: Carolyn W.T. Lee-Parsons, Erin J. Cram

Related Departments:Bioengineering, Chemical Engineering