Posts tagged Technology Transfer Office
A team led by the University of Colorado Boulder has been awarded $9.2 million over five years from the U.S. Department of Energy to research modifying E. coli to produce biofuels such as gasoline.
“This is a fantastic opportunity to take what we have worked on for the past decade to the next level,” said team leader Ryan Gill, a fellow of CU-Boulder’s Renewable and Sustainable Energy Institute, or RASEI. “In this project, we will develop technologies that are orders of magnitude beyond where we are currently.”
The team is working with a non-pathogenic strain of E. coli. Among the microbe’s more than 4,000 genes, the team is searching for a small set and how it can be manipulated in a combination of on and off states to change the bacteria’s behavior.
“E. coli is not going to want to make your biofuel at all,” said Gill, who’s also a CU-Boulder associate professor of chemical and biological engineering. “It doesn’t do that naturally. It’s programmed with thousands of genes controlling how it replicates. We’re figuring out what control structure we need to rewire in the bug to make it do what we want, not what it wants.”
Included in the team are Rob Knight, CU-Boulder associate professor of chemistry and biochemistry; Pin-Ching Maness, principal scientist at DOE’s National Renewable Energy Laboratory, or NREL; and Adam Arkin, physical biosciences director at DOE’s Lawrence Berkeley National Laboratory.
The researchers hope to engineer the production of ethylene and isobutanol in the modified E. coli. The two compounds are widely used commodities that can be converted into gasoline among other chemicals.
The greatest challenge is harnessing an efficient and inexpensive process that competes with abundant and low-cost fossil fuels like oil, according to Gill.
“Microorganisms and their genomes are incredibly complex machines,” said Gill. “The first step alone — of pinpointing the part of the E. coli genome that can help us make biofuels or other chemicals on a cost-competitive basis — is a daunting challenge. Then we have to determine if the results we want will take one year or decades, $5 million or $500 million.”
The team will be able to simultaneously identify numerous E. coli genes and the results of turning these genes on or off using advanced technologies. Many of the technologies have been developed by the researchers’ own labs.
The grant is the first of its kind from the DOE’s Office of Biological and Environmental Research and was awarded to only seven other research groups including teams led by MIT, Purdue University and the J. Craig Venter Institute.
In 2011, CU’s Technology Transfer Office named Gill an inventor of the year. In 2005, Gill won a National Science Foundation CAREER Award as well as a National Institutes of Health K25 Career Development Award for genomics research and teaching.
CU-BOULDER PYTHON STUDY MAY HAVE
IMPLICATIONS FOR HUMAN HEART HEALTH
A surprising new University of Colorado Boulder study shows that huge amounts of fatty acids circulating in the bloodstreams of feeding pythons promote healthy heart growth, results that may have implications for treating human heart disease.
CU-Boulder Professor Leslie Leinwand and her research team found the amount of triglycerides — the main constituent of natural fats and oils — in the blood of Burmese pythons one day after eating increased by more than fiftyfold. Despite the massive amount of fatty acids in the python bloodstream there was no evidence of fat deposition in the heart, and the researchers also saw an increase in the activity of a key enzyme known to protect the heart from damage.
After identifying the chemical make-up of blood plasma in fed pythons, the CU-Boulder researchers injected fasting pythons with either “fed python” blood plasma or a reconstituted fatty acid mixture they developed to mimic such plasma. In both cases, the pythons showed increased heart growth and indicators of cardiac health. The team took the experiments a step further by injecting mice with either fed python plasma or the fatty acid mixture, with the same results.
“We found that a combination of fatty acids can induce beneficial heart growth in living organisms,” said CU-Boulder postdoctoral researcher Cecilia Riquelme, first author on the Science paper. “Now we are trying to understand the molecular mechanisms behind the process in hopes that the results might lead to new therapies to improve heart disease conditions in humans.”
The paper is being published in the Oct. 28 issue of the journal Science. In addition to Leinwand and Riquelme, the authors include CU postdoctoral researcher Brooke Harrison, CU graduate student Jason Magida, CU undergraduate Christopher Wall, Hiberna Corp. researcher Thomas Marr and University of Alabama Tuscaloosa Professor Stephen Secor.
Previous studies have shown that the hearts of Burmese pythons can grow in mass by 40 percent within 24 to 72 hours after a large meal, and that metabolism immediately after swallowing prey can shoot up by fortyfold. As big around as telephone poles, adult Burmese pythons can swallow prey as large as deer, have been known to reach a length of 27 feet and are able to fast for up to a year with few ill effects.
There are good and bad types of heart growth, said Leinwand, who is an expert in genetic heart diseases including hypertrophic cardiomyopathy, the leading cause of sudden death in young athletes. While cardiac diseases can cause human heart muscle to thicken and decrease the size of heart chambers and heart function because the organ is working harder to pump blood, heart enlargement from exercise is beneficial.
“Well-conditioned athletes like Olympic swimmer Michael Phelps and cyclist Lance Armstrong have huge hearts,” said Leinwand, a professor in the molecular, cellular and developmental biology department and chief scientific officer of CU’s Biofrontiers Institute. “But there are many people who are unable to exercise because of existing heart disease, so it would be nice to develop some kind of a treatment to promote the beneficial growth of heart cells.”
Riquelme said once the CU team confirmed that something in the blood plasma of pythons was inducing positive cardiac growth, they began looking for the right “signal” by analyzing proteins, lipids, nucleic acids and peptides present in the fed plasma. The team used a technique known as gas chromatography to analyze both fasted and fed python plasma blood, eventually identifying a highly complex composition of circulating fatty acids with distinct patterns of abundance over the course of the digestive process.
In the mouse experiments led by Harrison, the animals were hooked up to “mini-pumps” that delivered low doses of the fatty acid mixture over a period of a week. Not only did the mouse hearts show significant growth in the major part of the heart that pumps blood, the heart muscle cell size increased, there was no increase in heart fibrosis — which makes the heart muscle more stiff and can be a sign of disease — and there were no alterations in the liver or in the skeletal muscles, he said.
“It was remarkable that the fatty acids identified in the plasma-fed pythons could actually stimulate healthy heart growth in mice,” said Harrison. The team also tested the fed python plasma and the fatty acid mixture on cultured rat heart cells, with the same positive results, Harrison said.
The CU-led team also identified the activation of signaling pathways in the cells of fed python plasma, which serve as traffic lights of sorts, said Leinwand. “We are trying to understand how to make those signals tell individual heart cells whether they are going down a road that has pathological consequences, like disease, or beneficial consequences, like exercise,” she said.
The prey of Burmese pythons can be up to 100 percent of the constricting snake’s body mass, said Leinwand, who holds a Marsico Endowed Chair of Excellence at CU-Boulder. “When a python eats, something extraordinary happens. Its metabolism increases by more than fortyfold and the size of its organs increase significantly in mass by building new tissue, which is broken back down during the digestion process.”
The three key fatty acids in the fed python plasma turned out to be myristic acid, palmitic acid and palmitoleic acid. The enzyme that showed increased activity in the python hearts during feeding episodes, known as superoxide dismutase, is a well-known “cardio-protective” enzyme in many organisms, including humans, said Leinwand.
The new Science study grew out of a project Leinwand began in 2006 when she was named a Howard Hughes Medical Institute Professor and awarded a four-year, $1 million undergraduate education grant from the Chevy Chase, Md.-based institute. As part of the award Leinwand initiated the Python Project, an undergraduate laboratory research program designed to focus on the heart biology of constricting snakes like pythons thought to have relevance to human disease.
Undergraduates contributed substantially to the underpinnings of the new python study both by their genetic studies and by caring for the lab pythons, said Leinwand. While scientists know a great deal about the genomes of standard lab animal models like fruit flies, worms and mice, relatively little was known about pythons. “We have had to do a lot of difficult groundwork using molecular genetics tools in order to undertake this research,” said Leinwand.
CU-Boulder already had a laboratory snake facility in place, which contributed to the success of the project, she said.
“The fact that the python study involved faculty, postdoctoral researchers, a graduate student and an undergraduate, Christopher Wall, shows the project was a team effort,” said Leinwand. “Chris is a good example of how the University of Colorado provides an incredible educational research environment for undergraduates.” Wall is now a graduate student at the University of California, San Diego.
Hiberna Corp., a Boulder-based company developing drugs based on natural models of extreme metabolic regulation, signed an exclusive agreement with CU’s Technology Transfer Office in 2008, licensing technology developed by Leinwand based on the natural ability of pythons to dramatically increase their heart size and metabolism.
Directed by Nobel laureate and CU Distinguished Professor Tom Cech, the Biofrontiers Institute was formed to advance human health and welfare by exploring critical areas of biology and translating new knowledge into practical applications. The institute is educating a new generation of interdisciplinary scientists to work together on solutions to complex biomedical challenges and to expand Colorado’s leadership in biotechnology. For more information on the Biofrontiers Institute visit http://cimb.colorado.edu/.
Aug. 15, 2011
Chemical and biological engineering students and faculty at the University of Colorado Boulder have launched several innovativetechnologies that are fueling Colorado’s economy by creating jobs and drawing significant funding to the state, including a $155 million investment in Sundrop Fuels in July.
Ten active companies have been created since 1997 based on technologies invented wholly or in part by chemical and biological engineering students and theirfaculty supervisors. More than 20 students have played an active role in developing these new ventures.
Chemical and biological engineering spinoff companies from CU-Boulder have raised nearly $410 million in follow-on funding, including grants, venture capital financing, U.S. Small Business Administration funding, and acquisitions, according to the University of Colorado’s Technology Transfer Office.
“Chemical and biological engineering research at the University of Colorado is contributing to the economic development of Colorado and the nation through the development of high-impact technologies and new companies that are creating job growth,” said department chair Christopher Bowman. “The Department of Chemical and Biological Engineering is commercializing technologies in critical areas of alternative fuels and chemicals, vaccines, therapeutic proteins and nanomaterials.”
One of the greatest success stories has been Copernican Energy, an ultra-clean, bio-based fuels company using a high-temperature radiant particle reactor to turn cellulosic material into green gasoline. The company was co-founded in2006 by CU Professor Al Weimer, CU student Chris Perkins who earned his doctorate the same year, and alumnus Mike Masterson, who earned a master’s degree in chemical engineering at CU in 1977.
The spinoff was acquired by Sundrop Fuels in 2008, and the Louisville-based company, which has 22 employees and a number of different contractors, received a $155 million investment, amounting to a 50 percent stake in the company, from Chesapeake NG Ventures Corp. in July. Sundrop Fuels previously had raised $62 million in support.
“The students are driving the entrepreneurial mission — they’re looking for inventions to make and then to commercialize,” Weimer said. “Many have seen their parents forced to take early retirement and so forth, and they are interested in working for themselves.”
OPX Biotechnologies is another large spinoff, having raised $60 million in two rounds of fundraising. Co-founded by Professor Ryan Gill and CU graduate Mike Lynch (Ph.D. ‘05, M.D. ’07), the Boulder-based company is using its technology to manufacture renewable bio-based chemicals and fuels that are lower cost, higher return and more sustainable than existing petroleum-based products. The company, which has 47 employees, signed a joint development agreement with Dow Chemical in April to prove the technical and economic viability of an industrial-scale process to produce acrylic acid using a fermentable sugar feedstock, a more environmentally friendly product than petroleum-based acrylic acid.
Other successful ventures spun off from the CU-Boulder chemical and biological engineering department include:
–BaroFold, an Aurora-based biotechnology company co-founded by CU-Boulder Professor Ted Randolph and John Carpenter of the University of Colorado Anschutz Medical Campus, has developed a technology that increases the safety of therapeutic proteins and lowers their production cost. Using $12 million in venture funding, BaroFold successfully completed Phase I human clinical trials for a protein-based therapy for multiple sclerosis. BaroFold is now working with Nuron Biotech Inc. and the Merck BioManufacturing Network to produce the protein for ongoing Phase III clinical trials.
–ION Engineering, a Boulder clean-tech company integrating ionic liquids in solutions to capture carbon and other contaminantsfrom gases, was founded based on technology developed in the laboratories of CU-Boulder professors Rich Noble and Doug Gin. ION recently announced a $3 million grant from the Department of Energy to demonstrate its novel solvent technology.
–ALD NanoSolutions, a Broomfield company co-founded by CU-Boulder professors Al Weimer and Steve George, along with CU alumni Mike Masterson (M.S. ’77) and Karen Buechler (Ph.D. ’99), is developing an atomic layer deposition coating technology that can apply designed coatings at the nanometer scale on particles of any size, creating various commercial opportunities for new materials development and integration. The company was awarded a $749,000 Phase II Small Business Innovation Research grant in June.
–RxKinetix, a Louisville-based company, was founded by a teamincluding CU-Boulder Professor Ted Randolph and Anschutz Medical Campus Professor Mark Manning to commercialize their microsphere-based drug delivery system. RxKinetix was acquired by Endo Pharmaceuticals in 2006.
Other spinoff companies with involvement from chemical and biological engineering include Aktiv-Dry and Mosaic Biosciences.
For more information about the CU-Boulder Department of Chemical and BiologicalEngineering go to http://www.colorado.edu/che.