CU News
News from the University of Colorado in Boulder.
CU : Some good news for doggie lovers
Dec 11th
clinical study to treat canine pain
A University of Colorado Boulder professor and her biomedical spinoff company Xalud Therapeutics Inc. of San Francisco are teaming up with a Front Range veterinarian to conduct a clinical study targeting an effective treatment for dogs suffering from chronic pain.
Distinguished Professor Linda Watkins of CU-Boulder’s psychology and neuroscience department said the study involves treating ailing dogs with a gene therapy using Interleukin-10, or IL-10, a protein and anti-inflammatory that both dogs and humans produce naturally. Watkins is working with veterinarian Robert Landry of Mountain Ridge Animal Hospital and Pain Management Center in Lafayette, who will be treating canine patients suffering from chronic and painful conditions, some of which already are being treated with various other medications with limited success.
Animals perceive and experience several levels of pain that are similar to humans, and chronic pain can be debilitating and also shorten the lives of pets, said Landry, one of only a handful of credentialed American Academy of Pain Management practitioners in Colorado. Landry currently is seeking Denver-Boulder area pet owners who have dogs suffering from chronic pain and who might be interested in participating in the study, which is free.
The new study is driven by research spearheaded by Watkins indicating a type of cell known as glial cells found in the nervous system of mammals plays a key role in pain. Under normal conditions, glial cells act as central nervous system “housekeepers,” cleaning up cellular debris and providing support for neurons, said Watkins. But glial cells also can play a pivotal role in pain enhancement by exciting neurons that both transmit pain signals and release a host of chemical compounds that cause problems like chronic neuropathic pain and other medical issues.
The team will use Xalud’s lead product candidate, XT-101, a gene therapy that harnesses the power of the potent anti-inflammatory IL-10 to normalize glial activity and eliminate neuropathic pain for up to 90 days with a single injection.
The gene therapy based on IL-10 has a number of advantages, including suppressing glial activity in the spinal cord, stimulating tissue regeneration and growth, decreasing the production of pro-inflammatory substances and increasing the production of anti-inflammatory substances, Watkins said. Landry and Watkins also have been working with the American Kennel Club on potential funding for additional clinical studies involving the treatment of chronic pain in dogs, said Watkins.
“We have already tested this new therapy in two pet dogs, and both have had remarkable reversals of their pain for long durations after a single injection of the therapeutic,” she said. “Our early peek at the potential of this therapeutic treatment in dogs shows essentially the same positive effects we have seen in laboratory rats used in our studies that have been treated with the therapy.”
Watkins said demonstrating the efficacy and safety of the new gene therapy in a second species of mammal is important in terms of moving it forward to eventually meet FDA regulations for human clinical trials.
In addition to studying what triggers glial cells to become activated and begin releasing pain-enhancing substances and ways to control chronic pain, Watkins and her research team recently discovered that clinically prescribed opioids also activate glial cells and cause them to release pain-enhancing substances. “Our ultimate goal is to find a means by which clinical pain control can be improved so as to relieve human suffering,” she said.
To contact Landry about possible participation in the study by family dogs suffering chronic pain and that might benefit from the experimental treatment, call the Mountain Ridge Animal Hospital at 303-665-4852.
For more information on CU-Boulder’s psychology and neuroscience department visit http://psych-www.colorado.edu/. For more information on Xalud Therapeutics Inc. visit http://www.xaludthera.com/. For more information on Mountain Ridge Animal Hospital visit http://www.mountainridgevet.com/.
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CU Boulder research team finds massive crevasses and bendable ice affect stability of Antarctic ice shelf
Dec 7th
Gaping crevasses that penetrate upward from the bottom of the largest remaining ice shelf on the Antarctic Peninsula make it more susceptible to collapse, according to University of Colorado Boulder researchers who spent the last four Southern Hemisphere summers studying the massive floating sheet of ice that covers an area twice the size of Massachusetts.
But the scientists also found that ribbons running through the Larsen C Ice Shelf – made up of a mixture of ice types that, together, are more prone to bending than breaking – make the shelf more resilient than it otherwise would be.
The research team from CU-Boulder’s Cooperative Institute for Research in the Environmental Sciences presented the findings Dec. 6 at the American Geophysical Union’s annual meeting in San Francisco.
The Larsen C Ice Shelf is all that’s left of a series of ice shelves that once clung to the eastern edge of the Antarctic Peninsula and stretched into the Weddell Sea. When the other shelves disintegrated abruptly – including Larsen A in January 1995 and Larsen B in February 2002 – scientists were surprised by the speed of the breakup.
Researchers now believe that the catastrophic collapses of Larsen A and B were caused, at least in part, by rising temperatures in the region, where warming is increasing at six times the global average. The Antarctic Peninsula warmed 4.5 degrees Fahrenheit since the middle of the last century.
The warmer climate increased meltwater production, allowing more liquid to pool on top of the ice shelves. The water then drained into surface crevasses, wedging them open and cracking the shelf into individual icebergs, which resulted in rapid disintegration.
But while the meltwater may have been responsible for dealing the final blow to the shelves, researchers did not have the opportunity to study how the structure of the Larsen A and B shelves may have made them more vulnerable to drastic breakups – or protected the shelves from an even earlier demise.
CU-Boulder researchers did not want to miss the same opportunity on the Larsen C shelf, which covers more than 22,000 square miles of sea.
“It’s the perfect natural laboratory,” said Daniel McGrath, a doctoral student in the Department of Geography and part of the CIRES research team. “We wanted to study this shelf while it’s still stable in order to get a better understanding of the processes that affect ice shelf stability.”
McGrath worked with CIRES colleagues over the last four years to study the Larsen C shelf in order to better understand how the warming climate may have interacted with the shelf’s existing structure to increase its vulnerability to a catastrophic collapse.
McGrath presented two of the group’s key findings at the AGU meeting. The first was the role that long-existing crevasses that start at the base of the shelf and propagate upward – known as basal crevasses – play in making the shelf more vulnerable to disintegration. The second relates to the way a type of ice found in areas called suture zones may be protecting the shelf against a breakup.
The scientists used ground penetrating radar to map out the basal crevasses, which turn out to be massive. The yawning cracks can run for several miles in length and can penetrate upwards for more than 750 feet. While the basal crevasses have been a part of Larsen C for hundreds of years, the interaction between these features and a warming climate will likely make the shelf more susceptible to future disintegration. “They likely play a really important role in ice-shelf disintegration, both past and future,” McGrath said.
The research team also studied the impact of suture zones in the ice shelf. Larsen C is fed by 12 distinct glaciers, which dump a steady flow of thick ice into the shelf. But the promontories of land between the glacial outlets, where ice does not flow into the shelf, allow for the creation of ribbon-like suture zones, which knit the glacial inflows together and which turn out to be important to the ice shelf’s resilience. “The ice in these zones really holds the neighboring inflows together,” McGrath said.
The suture zones get their malleable characteristic from a combination of ice types. A key component of the suture zone mixture is formed when the bottoms of the 12 glacial inflows begin to melt. The resulting freshwater is more buoyant than the surrounding seawater, so it rises upward to the relatively thinner ice zones between the glacial inflows, where it refreezes on the underside of the shelf and contributes to the chaotic ice structure that makes suture zones more flexible than the surrounding ice.
It turns out that the resilient characteristics of the suture zones keep cracks, including the basal crevasses, from spreading across the ice shelf, even where the suture zone ice makes up a comparatively small amount of the total thickness of the shelf. The CIRES team found that at the shelf front, where the ice meets the open sea, suture zone ice constitutes only 20 percent of the total thickness of the shelf but was still able to limit the spread of rifts through the ice. “It’s a pretty small part of the total ice thickness, and yet, it still has this really important role of holding the ice shelf together,” McGrath said.
Other CU researchers involved in the Larsen C project were Konrad Steffen, former director of CIRES; Ted Scambos, of CIRES and CU-Boulder’s National Snow and Ice Data Center; Harihar Rajaram, of the Department of Civil Engineering; and Waleed Abdalati, of CIRES.
CU team receives $9.2 million DOE grant to engineer E. coli into biofuels
Dec 4th
“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.