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Montana Molecular Lands $150K STTR Grant to Build GFP Probes

Nascent biotech Montana Molecular recently received a one-year, $150,000 Phase 1 Small Business Technology Transfer grant from the National Science Foundation to develop new fluorescent probes that target specific components in living cells.
The grant began on July 1.
The company will develop these tools by producing a library of green fluorescent-labeled proteins using a high-throughput insertion strategy. Montana Molecular is generating and validating about 50 probes every month, which is about the time it typically takes one experienced molecular biologist to build a single end-labeled probe using traditional methods, according to CEO Anne Marie Quinn. 
The company’s first goal is to develop these technologies for use as basic research tools by developing a library of genetically encoded fluorescent probes for studying protein localization and subcellular structures in living cells, said Quinn.
She said the company’s first collection of fluorescent probes will be available by early 2008.
The Phase 1 grant will allow the company to expand its research team and start to commercialize the probes. Quinn said that Montana Molecular plans to hire one full-time research scientist and one part-time bioinformaticist and data manager.
Quinn said that the company’s second goal is to provide fluorescent endpoints in living cells to show when a drug candidate activates a pathway triggered by a protein-protein interaction.
She said that the proof-of-principle studies have been completed, and the next step is to define which detectable protein-protein interactions would be most useful to the drug-discovery market. She said that finding the right biotech or pharmaceutical partner will be essential for the company to develop and market this second phase.
The company currently has fluorescent probes ready for market, but its business model is to develop strategic partnerships with larger companies to help sell them, said Quinn.
Quinn said that a few established companies are the “go-to places” for fluorescent reagents and “potential partners have been coming to us.” She declined to name any partners until Montana Molecular’s deals with them are finalized, perhaps later in the summer.
Molecular Montana’s business model would enable researchers interested in using a specific fluorescent protein to be able to search the company’s website, identify the protein of interest, and order it online, Quinn said. She said that this represents a significant savings compared to building a single fluorescent protein from scratch.
Quinn said that pricing will be dependent to some extent on licensing fees for the fluorescent proteins, but the company’s goal is to set a price that leaves no question about whether to build or buy. 
Molecular Montana uses a cassette based on a transposon that carries the green fluorescent protein to a target cDNA library. The transposon lands randomly in the cDNA library, creating internally labeled cDNAs.
She said that not only are these labeled proteins generated at a significantly greater speed using this technique compared to traditional methods, but when the probes are validated, many proteins that are known to function incorrectly as an end-labeled protein work well when the tag is attached somewhere in the middle of the protein.
For example, when the G-protein is end-labeled with a GFP, it does not function properly in the cell, said Quinn. The company’s internally labeled G-protein probe changes localization in response to activation, she added.
Quinn said that when a researcher tries to build a fluorescent fusion protein in the traditional way by “jamming” the GFP onto one of the ends of the protein, and the fusion protein doesn’t localize properly, no rational way exists to determine where the protein would tolerate the GFP. In Montana Molecular’s approach, the screen dictates which proteins localize correctly.
Once the fluorescent protein is sequenced, it is characterized in terms of its function and its target, Quinn said. The first step is tagging the cDNA library with the fluorescent probe, and the second step is the validation and characterization that is done with imaging and bioinformatics.
In an e-mail to CBA News, Vicki Singer, business director for labeling and detection at Invitrogen subsidiary Molecular Probes, said that her company is "very familiar with Montana Molecular and its transposon-based GFP fusion generation technology, and [is] impressed with the underlying technology itself.

The company is generating and validating about 50 probes every month, which is about the time it typically takes one experienced molecular biologist to build a single end-labeled probe using traditional methods.

“We feel that this technology has the capability to permit development of fluorescent protein fusions not previously amenable to GFP tagging, due to folding problems, poor biological activity, inadequate expression levels, et cetera,” she added.
According to Singer, Molecular Probes recently developed a new suite of reagents that combines four different colors of fluorescent proteins with signal peptides that target the proteins to specific cellular compartments.
These new products, called Organelle Lights reagents, target nuclear and plasma membranes, endoplasmic reticulum, mitochondria, Golgi bodies, peroxisomes, and other subcellular compartments, she said. Fusion protein genes are cloned into the BacMam delivery system, which labels different types of living cells with high spatial and temporal resolution.
“We feel that our relationship with Montana Molecular opens up the door for the creation of new BacMam reagents for use in co-localization, translocation, and biosensor studies,” said Singer. “Similarly, we may be able to provide libraries of ready-to-use fusion proteins along with custom construction of fusions to the research community."
Looking Ahead
Montana Molecular, founded in 2004, has been collaborating with Thom Hughes at Montana State University, who has been developing genetically encoded fluorescent technologies for over a decade. Hughes is also an advisor to the company, according to its website.
Quinn said that over the next two to three years, Montana Molecular plans to continue building its IP portfolio. It will also continue to build strategic partnerships to help it develop and market additional products.
In terms of additional financing, Quinn said the company can either apply for a Phase 1B STTR grant at the end of the year or apply for a Phase 2 grant. It also has been negotiating with its strategic partners, which involves financial support. The company has submitted other grants and received funding from the state of Montana. It has received some private funding as well.
“We’re not too interested in venture capital right now,” said Quinn. “Our model is not one where we have to grow fast. We are growing, but we are more interested in sustainable, incremental growth. We might entertain VC funding in the future but we are not completely convinced that it’s an appropriate model for us right now.”  

Quinn did not elaborate on grants and funding issues.

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