Stimulus Grant to Help MSU Team Improve Drug Development from Plants

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Dean Dellapenna (view larger image)

MSU scientists are receiving nearly $3 million from the National Institutes of Health (NIH) to uncover how several popular plants make medicinal compounds.

The funding, part of a larger $6 million award via the American Recovery and Reinvestment Act, will provide scientists the resources to understand exactly which genes are involved in the synthesis of medicinal chemicals in several plants and clear the way for cheaper and more effective ways to produce drugs.

“Many plants make compounds that we use directly as medicines or that we modify slightly to create widely used medicines, but in almost all cases, we do not understand how the plants synthesize these compounds,” said MAES biochemistry scientist Dean DellaPenna, one of three principal investigators on the grant. “Identifying and understanding the genes involved in the synthesis of these plant compounds is a first step that can lead to new drug development and increased production efficiency.”

The research team—including researchers at the University of Kentucky and the Massachusetts Institute of Technology—is using three key techniques:

  • Transcriptomics allows scientists to learn which of the roughly 30,000 genes in a plant are actively being transcribed into RNA in a tissue and the exact expression level of each gene.
  • Metabolomics allows assessment of the types and levels of several hundred chemicals within the tissue (some of which are medicinal compounds, some of which are biosynthetic precursors).
  • Bioinformatics then combines these two very large data sets to figure out which genes are being expressed in concert with specific chemicals and thereby provide scientists with a short list of those genes most likely to be involved in synthesis of the medicinal compound of interest.

The research team then will conduct additional research to demonstrate each of these genes’ individual functions in detail and provide the basis for synthetic biology techniques needed to develop drugs.

“Plants are better chemists than people, so understanding the biosynthesis and exactly how plants are able to do this provides a powerful base of knowledge for improving medicine and health,” said Dave Dewitt, associate dean for research in the College of Natural Science. “Seeing the genome of a plant is like looking at a list of 30,000 parts without the instruction manual of how it all comes together to work.” The research relies on high-throughput DNA sequencers at MSU. Each experiment can yield as many as 500 million base pairs of DNA sequence, and the entire project will generate approximately 240 billion base pairs of information, the equivalent of roughly 80 human genomes.

The 14 plants the scientists will be researching include Digitalis purpurea (foxglove), from which the heart drug digitoxin is derived; Atropa belladonna, from which the drug atropine is produced; and Catharanthus roseus (periwinkle), from which the anti-cancer drugs vincristine and vinblastine are obtained. More information can be found at http://medicinalplantgenomics.msu.edu.

MSU is receiving $2.9 million of the $6 million Grand Opportunity grant from the NIH. Other co-investigators on the grant are Joseph Chappell, from the University of Kentucky; Sarah O’Connor, the Massachusetts Institute of Technology; and Robin Buell, MAES plant biologist.

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