MSU biochemistry professor Dean DellaPenna. Courtesy photo.

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Scientists on the grant -- including researchers at the University of Kentucky and the Massachusetts Institute of Technology -- are 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.

"Ongoing advancements in life sciences technology allows us to efficiently interrogate these very large parts lists and efficiently do experiments on a scale that just wasn't possible three years ago," Dewitt said. "DNA sequencing and metabolite analysis has become immensely more efficient to a point where we can make new discoveries using methods and approaches previously not easily employed in metabolic engineering."

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 include Joseph Chappell from the University of Kentucky, Sarah O'Connor from the Massachusetts Institute of Technology and Robin Buell of MSU.

NIH Grand Opportunity grants are awarded to fund short term projects with specific goals that have the potential to significantly advance biomedical research in a short period of time.

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