By Doug Macron
Aiming to develop discoveries made in his lab at Duke University for practical applications, plant researcher Philip Benfey a few years ago co-founded the agricultural biotech firm GrassRoots Biotechnology.
While his previous work with microRNAs doesn't specifically factor into GrassRoots' projects, Benfey, who is also the firm's CEO, expects that these and other non-coding RNAs will eventually prove to be a key aspect of the company's efforts in gene-discovery and -expression.
“The company was started in 2007 with the idea that proprietary technology that I developed in my lab at Duke … could be used to address real-world problems, particularly food security, climate change, carbon sequestration, and alternative energy,” Benfey told Gene Silencing News.
Specifically, GrassRoots is focusing on plant roots with an eye toward improving their structure, about which “relatively little is known,” he said.
At Duke, Benfey's lab has made discoveries related to how cells in roots divide and differentiate, including the identification of two transcription factors, Short-root and Scarecrow, that work together to control radial patterning and the specification of a stem-cell niche called the quiescent center.
Additionally, last year he and his colleagues reported in Nature on how microRNAs travel between cells in the model plant Arabidopsis (GSN 4/22/2010). According to that paper, Short-root was found to travel from the plant's vascular cylinder to the surrounding endodermis, where it activates Scarecrow.
Together, the transcription factors activate two miRNAs, miR-165a and miR-166b, which move back to the vascular cells, degrading target mRNAs encoding certain transcription factors and thereby determining cell types in a dose-dependent manner.
Within GrassRoots, Benfey is aiming to leverage these and other findings to enable high-resolution gene-expression analysis and root phenotyping, and has already developed an array technology for analyzing genes within plant roots.
The so-called RootArray system comprises a “multi-well plate that holds dozens of seedlings in a defined growth medium,” according to GrassRoots. This enables researchers to monitor gene expression in the root in 3D over time, and to introduce different nutrients and chemicals that may affect gene expression and plant development.
The company is also engaged in gene-discovery research in switchgrass, which is often grown as a biomass crop for biofuels. GrassRoots specifically aims to find genes that influence the time it takes switchgrass to grow roots, as well as the length of the roots. In doing so, the company hopes to be able to identify ways to speed the time to harvest and increase the amount of carbon sequestration of the grass.
Benfey noted that miRNAs haven't been a “major focus” for the company up until now. However, “as we move forward looking at comprehensive solutions to gene expression, microRNAs are definitely what we are investigating,” and they are expected to play “a very important role” along with other ncRNAs.
For example, when it comes to “trying to produce predictable and tunable [gene]-expression solutions,” the agbio field is still relying on “workhorse promoters,” which are “genes out of viruses that were discovered 30 years ago,” he said.
“There is a lot of potential for improvement there and a lot of basic work, some of which will involve small, non-coding RNAs, including microRNAs, to make these [solutions] predictable and specific,” he noted.
Currently, GrassRoots has 22 full-time employees, eight of which hold PhDs, Benfey said. Although the company's initial funding came from government grants, in 2009 it established a research and development alliance with Monsanto focused on identifying “novel genetic elements, including promoters and genes, which can enable crops to express traits that enhance and protect yield,” according to the companies.
That arrangement had an initial three-year term, but was recently extended for another two years, Benfey said.
Meanwhile, Benfey continues to divide his time between the company, headquartered in Durham, and Duke.
At GrassRoots, “my job is one of strategy guidance at a higher level, and, for the moment, we seem to be able to handle that as a part-time” basis,” he said.
“I don't think this will be forever; my guess is in the next year or two we will need a full-time CEO,” he added. “But at the moment, [this arrangement] allows us to run leaner.”
GrassRoots isn't the only agbio firm looking to miRNAs. In 2008, Rosetta Genomics established Rosetta Green to use its miRNA technology and know-how in the plant science field, and earlier this year the company went public in Israel (GSN 2/24/2011).
According to Rosetta Green, its projects include improving crop plant traits such as tolerance to environmental stress and the efficiency with which the plants use fertilizer; the identification of molecules that can be used to enhance crop breeding; and the development of plants and algae with improved biofuel-related traits.
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