SLAS members Anne Marie Quinn and Thomas Hughes carved a place for their company, Montana Molecular, far from the biotech hubs that launched their careers. The company put down roots on Quinn's vision that the tools of science drive progress and the scientists who adopt those tools early have a professional advantage.
Montana Molecular spent the past year making headlines with its genetically encoded fluorescent biosensors and probes for cell-based assays and live cell imaging, which help drug discovery scientists to observe and measure cell-signaling processes. The company has experienced steady momentum since its launch in 2005 by husband-and-wife team Anne Marie Quinn, M.P.H., founder and CEO, and Thomas E. Hughes, Ph.D., a senior advisor and scientific officer. Since January 2013, the company's profile has increased and the team is reaping rewards for their hard work.
First, the couple attended the SLAS2013 Conference and Exhibition where they were named finalists for the SLAS Innovation Award. Their entry, "A Multiplexed Fluorescent Assay for Independent Second Messenger Systems: Decoding GPCR Activation in Living Cells," was later published in the Journal of Biomolecular Screening (JBS), one of SLAS's two MEDLINE-indexed scientific journals, and was one of six scientific manuscripts featured in a JALA and JBS Author Meet and Greet session in the SLAS2014 Member Center.
Then SLAS's Journal of Laboratory Automation (JALA) named Montana Molecular's work to its list of The 2013 JALA Ten. This is an annual recognition of the 10 top technological breakthroughs across a spectrum of scientific fields. Montana Molecular's selected work, "Simultaneous Detection of Ca2+ and Diacylglycerol Signaling in Living Cells," highlighted their development of direct, kinetic readouts that can be multiplexed to detect multiple components of cell signaling in disease-relevant cells.
"SLAS has been an incredible help in spreading the word about our technology," says Quinn. "Being named SLAS Innovation Award finalists gave us validation that we were on the right track and earned us an invitation to the SLAS Third Annual Asia Conference and Exhibition held in June 2013 in Shanghai, China. We made incredible contacts in China and learned a lot about our market in Asia too."
The timing of this recognition was ideal as it provided support material to include in the company's grant writing efforts. "The goals of our Phase II funding from the National Institutes of Health are to optimize our biosensors and develop better live-cell assay products for drug discovery and basic research," Quinn says.
She shares that the company further expanded this research thanks to funding from a Small Business Innovation Research (SBIR) Phase 1/Phase 1B grant from the National Science Foundation (NSF). "In this project, we were able to expand our biosensor technologies to detect additional G protein-coupled receptors' (GPCR) second messengers that signal via Gi and Gs proteins," she says. "These results further enabled the multiplex capabilities of our assay products and enabled us to file our second patent late in 2013. Our SBIR Phase II application to NSF is under review, and we can't wait to resume work on this project."
To keep their momentum going, Quinn and Hughes attended SLAS2014 in San Diego, which helped reconnect them with everyone they met last year. "SLAS helped us cement contacts and promote our technology. The exhibit hall is one of the best features of the meeting – we got to see all the new technology that we would never get to see living in Montana. In fact, one company we learned about at SLAS2014 just came to visit us," Quinn continues. "We probably get more from SLAS than anyone else at the meeting."
She points to several connections made at SLAS2014, from finally meeting JBS author Lisa Minor, Ph.D., president of In Vitro Strategies, with whom Quinn has exchanged ideas remotely for the last year, to planning a collaboration with SLAS2014 Sponsor Cisbio, and presenting a poster with SLAS sponsor BioTek. The poster, "Automated Fluorescence Imaging of GPCR Dependent Second-Messenger Systems," gave Montana Molecular a venue to talk about using their assays on BioTek's plate-reading instruments. "Every time I walked by that poster, there was a big crowd," Quinn reports. Biotek's Cytation 3 imaging plate reader produces multichannel measurements of fluorescence and images from living cells, so Montana Molecular's assays can be used in either mode on this instrument. Montana Molecular also presented a poster entitled "GPCR Signal Deconvolution: New Sensors to Enable Agonist Bias Detection in Living Cells" that emphasized the importance of multiplex assays that report when different agonists act through the same receptor to activate different signaling pathways.
She encourages communication between Society members. "We have the same goals," she says. "People I have met through SLAS have been more than willing to work with us. It's important to make and cultivate these contacts, particularly if you are living and working outside the geographic centers of the biotech world."
Surrounded by mountain peaks, rivers and Yellowstone National Park's backyard, Bozeman, MT is far from U.S. biotech hubs. Although its geography and lifestyle suited Quinn and Hughes' personal life, options for their professional goals were slim when they first settled there in 2003. "Bozeman is a frontier when it comes to biotech companies," Quinn explains. "That being said, there are excellent cell biology and neuroscience departments at both Montana State University (MSU), here in Bozeman, and also at University of Montana (UMT) in Missoula (three hours northwest of Bozeman). The McLaughlin Research Institute in Great Falls, MT is renowned for their transgenic mouse facility." Bozeman seemed like an environment ripe for a new biotech company to be planted and Quinn and Hughes arrived with 20 years of career and academic experience to make it happen.
Quinn and Hughes met while working at The Salk Institute in San Diego, CA. Quinn had been promoted to the head of Salk's Biocomputing Core Facility and was collaborating with post docs working in Stephen F. Heinemann's Molecular Neurobiology Laboratory. One of these post-docs was Hughes. The couple hit it off, married and left Salk for Yale School of Medicine where Hughes accepted a faculty position and Quinn worked in bioinformatics.
As her work responsibilities grew, Quinn decided that additional science education would help to expand her knowledge and career options. "I had learned the science as I went along, but I realized that graduate school would strengthen that knowledge," she continues. She enrolled in the Yale School of Public Health, focusing on biostatistics and genetic linkage analysis. She earned her master's of public health in biostatistics in 2001.
As the years of academic accomplishment and career progress unfolded, Quinn and Hughes, both West Coast natives, longed to return to the West and put their collective knowledge to new use. As Quinn explains, "we got as far as Bozeman," settled in and began to work – Quinn as an application scientist for Accelrys, a software company based in San Diego, and Hughes as a professor at MSU during the academic year in the Department of Cell Biology and Neuroscience.
The idea for Montana Molecular began to bloom around the spouses' careers and research. Quinn's new job piqued her interest in business and the tools for drug discovery. "I worked with Kevin Kendall, who was developing MacVector for sequence analysis, and I also learned more about three-dimensional protein modeling and receptor-ligand interaction," she explains. The job required her to travel to pharmaceutical and biotech companies to provide support for their sales teams. "At a certain point, I realized that I wanted to move on and start my own company."
Meanwhile, Hughes had been working with fluorescent proteins for over a decade. "We both thought that fluorescent protein technologies had great potential for drug discovery, particularly as stem cell technologies were advancing and interest in screening primary cells was growing," explains Quinn. "We finally settled on using single fluorescent protein biosensors because the signal to noise is so high that they can be readily detected on standard fluorescence plate readers and imaging systems that our customers already own. We took it a step further by combining different colored fluorescent protein sensors to produce multiplex assays. Because they are genetically encoded, our biosensors can be targeted to virtually any cell type, too."
Quinn's mission was to build and deliver robust and easy-to-use ?uorescent biosensors and probes for cell-based discovery. She launched Montana Molecular in 2005, and the company received its ?rst round of funding in a Phase 1 Small Business Technology Transfer (STTR) grant from the NSF in 2007. The STTR helped them to build hundreds of ?uorescent probes that could be used to label a wide variety of cell structures and proteins of interest. Montana Molecular licensed these probes in December 2012 to Cell BioLabs Inc.
Licenses were the first major challenge for Quinn during the start up. Affordable access to the intellectual property (IP) covering fluorescent proteins derived from jellyfish was next to impossible. "Early on there were some big companies that bought up the rights to those proteins. They didn't develop the IP, which was created using public money, they just held on to it," she explains. "When we approached them, they placed prohibitively expensive licenses on these products. These situations are a big obstacle to innovation and commercializing new technology."
The good news is that many patents on this IP will soon expire. Further good news is that the discovery of new fluorescent proteins with better quantum efficiencies have emerged in smaller, more progressive companies, such as Allele Biotechnologies in San Diego, which offers mNeonGreen, a high performance monomeric yellow-green fluorescent protein that is derived from a tetrameric fluorescent protein from amphioxus. "The team at Allele just wants to see people get out there and innovate," says Quinn, adding that another good resource is Evrogen Biotechnologies in Russia, which supplies red fluorescent protein (TagRFP), a monomeric red (orange) fluorescent protein generated from the wild-type RFP from sea anemone. "These companies are cooperative and have turned this whole business around."
The financial challenge of protecting their own IP was another almost insurmountable task for the small, start-up company. "It's so expensive to provide needed protection for your work," she says. "You're not allowed to put legal expenses on an SBIR grant. If you don't have outside investors, you have to raise money to apply for patents by yourself."
Maintaining steady funding is another hurdle in Montana's biotech frontier. "In the absence of venture capital, you have to build a business here by pulling yourself up by your boot straps. You have to have that willingness to operate a lean company," she continues. "We need to write grants and develop relationships with larger companies that might benefit from our work and be interested in partnering with us to get it done."
On the other hand, where capital is scarce, an entrepreneurial spirit is abundant. For example, starting a company in Montana is quite different from starting one in a biotech hub such as San Diego, Quinn notes. "We would be just another biotech company there," she continues. "If you start a biotech company in Montana, the governor and our senators take notice and will help with networking opportunities. If you are awarded an SBIR, the state of Montana will kick in matching funds too."
In 2009, legislation passed allowing Montana to match federal SBIR grant dollars providing funds to companies such as Montana Molecular that needed to invest heavily in R&D before bringing a product to market. In addition to this assistance, Quinn also credits the funding received from business development entities such as: the Montana Board of Research and Commercialization (MBRCT), which generated preliminary results that made it possible for her company to compete successfully at the national level for SBIR grants; and TechRanch, which reviewed her early business proposals.
"All these organizations were helpful. There were times when there was a gap in funding from grants I had from the NIH or from the NSF, and state resources helped us get to the next level," Quinn explains.
Besides the technology that Montana Molecular continues to develop, there is for Quinn an appealing aspect of making an impact on the state's economy by developing biotech jobs.
"Hundreds graduate from MSU and UMT every year, and they have to leave the state to find a job," she says, mentioning team member Paul Tewson as an example. Tewson, first author/primary inventor on all papers and patents relating to Montana Molecular's technologies, was raised in Bozeman, graduated from MSU and has had the opportunity to remain in the state, thanks to Montana Molecular. "Most people who go to school here were born and raised here," Quinn observes. "While it's great to leave for a while, a lot of people want to come back."
What Bozeman-ites want to return to is "one of the most beautiful places on Earth," says Quinn. "Yellowstone National Park is right in our backyard. We have three rivers that flow through our valley," she says. When the stress of entrepreneurship and research press in, the Quinn-Hughes team hits the trail, donning skis or hiking boots. Sometimes the couple opts for waders and searches out a quiet stream for fishing. This winter Quinn and Hughes followed the road that runs along the Gallatin River and explored West Yellowstone via snow coach.
"The National Park Service closes the roads down in winter so you have to travel by snow coach, and that takes you down the park's snowy roads to a lodge near Old Faithful that stays open through the winter," Quinn says. From there, they ventured into the geyser basin on cross country skis. "It's so beautiful in winter! The contrast of the cold air and the hot steam is amazing, and the wildlife is incredible," she says, adding that they enjoyed watching wolves, elk, bison and the occasional bobcat as the animals strayed into view. "It could take a lifetime to explore Yellowstone, it's so huge. There are large parts of it we haven't even seen yet."
Such breaks are a regular part of the couple's life, because boot-strapping is hard work. "I had a grant to write the weekend of our trip into Yellowstone, so I took my computer and sat in the lodge working on it," Quinn says. "It's like a vacation, but you do still get pulled into work."
She concludes there is no place she'd rather be. "This is a great time in the profession. Particularly to be a woman in science right now is exciting. There were so few female scientists when I was young, so I appreciate having this opportunity to bring young women into science through Montana Molecular," Quinn says. "It's rewarding to build something from the ground up. It's wonderful to have an impact on the young people we can hire, to get people excited about our technology and advance new products that have impact far beyond the borders of our state. We love this process of creating something new, and bringing recognition from the biotech industry to the state of Montana."
April 28, 2014