Posts tagged DNA
CU study: New public gut bacteria study expected to reach around world
Nov 25th
Ever wondered who is living in your gut, and what they’re doing? The trillions of microbial partners in and on our bodies outnumber our own cells by as many as 10 to 1 and do all sorts of important jobs, from helping digest the food we eat this Thanksgiving to building up our immune systems.
In association with the Human Food Project, researchers at the University of Colorado Boulder along with researchers at other institutions around the world are launching a new open-access project known as “American Gut” in which participants can get involved in finding out what microbes are in their own guts and what they are doing in there.
The project builds on previous efforts, including the five-year, $173-million NIH-funded Human Microbiome Project, to characterize the microbes living in and on our bodies, said Associate Professor Rob Knight of CU-Boulder’s BioFrontiers Institute. But unlike other projects that have focused on carefully chosen test subjects with a few hundred people, this project allows the public to get involved and is encouraging tens of thousands of people to do so, Knight said.
“Galileo saw outer space through his telescope, and we want to see the inner space of your gut through modern genetics,” said Rob Dunn, a scientist at North Carolina State University and a collaborator on the project. The new project will be “crowd-funded” by individuals interested in learning more about their own gut bacteria and by others who simply want to contribute to the project, said Dunn.
“By combining the crowd-funding model with the open-access data analysis model that we pioneered with the Earth Microbiome Project, we can finally give anyone with an interest in his or her microbiome an opportunity to participate, whether by contributing samples or by looking at the data,” said Knight, also a Howard Hughes Medical Institute Early Career Scientist.
Public interest is immense, says the research team. 18,000 people have already signed up to receive more information by email about the project when it launches. “The American Gut project builds on the Human Microbiome Project by allowing anyone to participate, and will let the public join in the excitement of this new field,” said Lita Proctor, program director for the Human Microbiome Project. “We can expect this to lay the groundwork for all sorts of fascinating studies in the future, that others will in turn build on.”
The American Gut project is an opportunity for the “citizen scientists” working with team of leading researchers and labs throughout the United States to help shape a new way of understanding how diet and lifestyle may contribute to human health through each person’s suite of trillions of tiny microbes, say the researchers. A key aspect of the project is to understand how diet and lifestyle, whether by choice — like athletes or vegetarians — or by necessity, including those suffering from particular autoimmune diseases or who have food allergies, affect peoples’ microbial makeup, said Knight.
“This will be the first project of its kind that might be able to address this question at such a large scale,” said Jeff Leach, founder of the Human Food Project and co-founder of American Gut. The gut microbiome has been linked to many diseases, including obesity, cancer, and inflammatory bowel disease — all of which are much more common in Western populations, he said.
“We should start thinking about diets not only from the perspective of what we should eat, but what we should be feeding our entire gut microbial systems,” said Leach. A key aspect of the project is to integrate studies of Americans of all shapes and sizes with studies of people living more traditional lifestyles in Africa, South America and elsewhere, he said.
The steep decline in the cost of DNA sequencing and recent advances in computational techniques allow for the analysis of microbial genomes orders of magnitude cheaper than was possible only a few years ago, said Knight. Sequencing is now getting cheap enough — participants who donate $99 or more can expect to get tens of thousands of sequences from microbes in their gut — that participants can include their families and even their pets, Knight said.
Doctoral student Daniel McDonald is one of several CU-Boulder students who will be involved in the effort. “I am excited to have the opportunity to develop new computational tools in order to further explore this frontier,” said McDonald, who is in the Interdisciplinary Quantitative Biology program at the BioFrontiers Institute.
“I am pleased to participate in this pioneering effort that marries the vast interest of the public in science with questions that are worth answering about human health and nutrition,” said Martin Blaser, chair of the Department of Medicine and professor of microbiology at New York University. “Through this consortium, the technical and intellectual resources are there to lead to important new knowledge.”
The project will seek to build on a growing canine and feline database as well. “The majority of data we currently have on the dog and cat microbiomes has come from a handful of small studies in research or clinically ill animals,” said Associate Professor Kelly Swanson of the Department of Animal Sciences and Division of Nutritional Sciences at the University of Illinois at Urbana-Champaign. “This study will apply the technology to free-living pets, where diet, genetics, and living environment are quite different from household to household.
“This research may identify important trends not possible with lab-based studies, and help guide us on how to feed our pets in the future,” said Swanson.
The backdrop to the project is the radical decline in the cost of DNA sequencing, which allows analysis of microbial genomes orders of magnitude cheaper than was possible only a few years ago, and recent advances in computational techniques. Participants in the project include many of the key players in the Human Microbiome Project and research facilities around the world.
To learn more about participating in or contributing to the project visit https://www.indiegogo.com/americangut. For a list of additional collaborators on the project visithttp://humanfoodproject.com/the-people/collaborators/.
[includeme src=”http://c1n.tv/boulder/media/bouldersponsors.html” frameborder=”0″ width=”670″ height=”300″]
CU Boulder researchers uncover new target for cancer research
Oct 25th
Researchers in the two scientists’ laboratories collaborated to find a patch of amino acids that, if blocked by a drug docked onto the chromosome end at this location, may prevent cancerous cells from reproducing. The amino acids at this site are called the “TEL patch” and once modified, the end of the chromosome is unable to recruit the telomerase enzyme, which is necessary for growth of many cancerous cells.
“This is an exciting scientific discovery that gives us a new way of looking at the problem of cancer,” Cech said. “What is amazing is that changing a single amino acid in the TEL patch stops the growth of telomeres. We are a long way from a drug solution for cancer, but this discovery gives us a different, and hopefully more effective, target.”
Cech is the director of the BioFrontiers Institute, a Howard Hughes Medical Investigator and winner of the 1989 Nobel Prize in chemistry.
Co-authors on the study include postdoctoral fellows Jayakrishnan Nandakumar and Ina Weidenfeld; University of Colorado undergraduate student Caitlin Bell; and Howard Hughes Medical Institute Senior Scientist Arthur Zaug.
Telomeres have been studied since the 1970s for their role in cancer. They are constructed of repetitive nucleotide sequences that sit at the ends of our chromosomes like the ribbon tails on a bow. This extra material protects the ends of the chromosomes from deteriorating, or fusing with neighboring chromosome ends. Telomeres are consumed during cell division and, over time, will become shorter and provide less cover for the chromosomes they are protecting. An enzyme called telomerase replenishes telomeres throughout their lifecycles.
Telomerase is the enzyme that keeps cells young. From stem cells to germ cells, telomerase helps cells continue to live and multiply. Too little telomerase produces diseases of bone marrow, lungs and skin. Too much telomerase results in cells that over proliferate and may become “immortal.” As these immortal cells continue to divide and replenish, they build cancerous tumors. Scientists estimate that telomerase activation is a contributor in up to 90 percent of human cancers.
To date, development of cancer therapies has focused on limiting the enzymatic action of telomerase to slow the growth of cancerous cells. With their latest discovery, Cech and Leinwand envision a cancer drug that would lock into the TEL patch at chromosome ends to keep telomerase from binding there. This approach of inhibiting the docking of telomerase may be the elegant solution to the complex problem of cancerous cells. Cech, a biochemist, and Leinwand, a biologist, joined forces to work on their latest solution.
“This work was really made possible by the fact that our labs are so close,” Leinwand said. “My lab was able to provide the cell biology and understanding of genetics, and Tom’s lab allowed us to explore the biochemistry. We have a unique situation at BioFrontiers where labs and people comingle to make discoveries just like this.”
Leinwand is the chief scientific officer of the BioFrontiers Institute and a professor of molecular, cellular and developmental biology.
Researchers at the University of Colorado have a significant history in developing marketable biotechnologies. Cech founded Ribozyme Pharmaceuticals Inc. Leinwand co-founded Myogen with CU professor Michael Bristow, Hiberna and recently launched MyoKardia (http://www.myokardia.com/about.php).
The BioFrontiers Institute is an interdisciplinary institute housed at the Jennie Smoly Caruthers Biotechnology Building at CU-Boulder. The institute is dedicated to training the next generation of interdisciplinary scientists through its IQ Biology Interdisciplinary Quantitative Biology Ph.D. program. For more information about BioFrontiers visithttp://biofrontiers.colorado.edu
–
New CU-Boulder study clarifies diversity, distribution of cutthroat trout in Colorado
Sep 24th
A novel genetic study led by the University of Colorado Boulder has helped to clarify the native diversity and distribution of cutthroat trout in Colorado, including the past and present haunts of the federally endangered greenback cutthroat trout.
The study, led by CU-Boulder postdoctoral researcher Jessica Metcalf, was based largely on DNA samples taken from cutthroat trout specimens preserved in ethanol in several U.S. museums around the country that were collected from around the state as far back as 150 years ago. The new study, in which Metcalf and her colleagues extracted mitochondrial DNA from fish to sequence genes of the individual specimens and compared them with modern-day cutthroat trout strains, produced some startling results.
The biggest surprise, said Metcalf, was that the cutthroat trout native to the South Platte River drainage appears to survive today only in a single population outside of its native range — in a small stream known as Bear Creek that actually is in the nearby Arkansas River drainage. The strain from Bear Creek is thought to have been collected from the South Platte River drainage in the 1880s by an early hotelier who stocked the fish in a pond at the Bear Creek headwaters to help promote an early tourist route up Pikes Peak.
“We thought one way to get to the question of which cutthroat trout strains are native to particular drainages was to go back to historical samples and use their DNA as a baseline of information,” said Metcalf of the chemistry and biochemistry department and a former postdoctoral researcher at the Australian Centre for Ancient DNA. “Our study indicates the descendants of the fish that were stocked into Bear Creek in the late 1800s are the last remaining representatives of the federally protected greenback cutthroat trout.”
A second, key set of data was all of the Colorado cutthroat trout stocking records over the past 150 years, a task spearheaded by study co-author and fish biologist Chris Kennedy of the U.S. Fish and Wildlife Service. Between 1889 and 1925, for example, the study showed that more than 50 million cutthroat trout from the Gunnison and Yampa river basins were stocked in tributaries of all major drainages in the state, jumbling the picture of native cutthroat strains in Colorado through time and space.
Originating from the Pacific Ocean, cutthroat trout are considered one of the most diverse fish species in North America and evolved into 14 recognized subspecies in western U.S. drainages over thousands of years. In Colorado, four lineages of cutthroats were previously identified: the greenback cutthroat, the Colorado River cutthroat, the Rio Grande cutthroat and the extinct yellowfin cutthroat.
The museum specimens used in the study came from the California Academy of Sciences, the Smithsonian Museum of Natural History in Washington, D.C., the Academy of Natural Sciences in Philadelphia and the Harvard University Museum of Comparative Zoology. Colorado cutthroat trout specimens were collected by a number of early naturalists, including Swiss scientist and former Harvard Professor Louis Agassiz and internationally known fish expert and founding Stanford University President David Starr Jordan.
The new study, published online today in Molecular Ecology, follows up on a 2007 study by Metcalf and her team that indicated there were several places on the Front Range where cutthroat populations thought to be greenbacks by fish biologists were actually a strain of cutthroats transplanted from Colorado’s Western Slope in the early 1900s.
Other co-authors on the new study included CU-Boulder Professor Andrew Martin and CU-Boulder graduate students Sierra Stowell, Daniel McDonald and Kyle Keepers; Colorado Parks and Wildlife biologist Kevin Rogers; University of Adelaide scientists Alan Cooper and Jeremy Austin; and Janet Epp of Pisces Molecular LLC of Boulder.
“With the insight afforded by the historical data, we now know with a great deal of certainty what cutthroat trout strains were here in Colorado before greenbacks declined in the early 20th century,” said Martin of CU’s ecology and evolutionary biology department. “And we finally know what a greenback cutthroat trout really is.”
Metcalf and her colleagues first collected multiple samples of tissue and bone from each of the ethanol-pickled trout specimens, obtaining fragments of DNA that were amplified and then pieced together like a high-tech jigsaw puzzle to reveal two genes of the individual specimens. The tests were conducted on two different continents under highly sterile conditions and each DNA sequencing effort was repeated several times for many specimens to ensure accuracy in the study, Metcalf said.
Roughly half of the study was conducted at CU-Boulder and half at the Australian Center for Ancient DNA at the University of Adelaide, where Metcalf had worked for two years. “By conducting repeatable research at two very different, state-of-the-art laboratories, we were able to show the Bear Creek trout was the same strain as the cutthroats originally occupying the South Platte River drainage.”
The Bear Creek trout strain is now being propagated in the Colorado Parks and Wildlife hatchery system and at the USFWS Leadville National Fish Hatchery.
In addition to identifying the Bear Creek cutthroat trout, Metcalf and her colleagues discovered a previously unknown cutthroat strain native to the San Juan Basin in southwestern Colorado that has since gone extinct. The study also confirmed that the yellowfin cutthroat, a subspecies from the Arkansas River headwaters that grew to prodigious size in Twin Lakes near Leadville, also had gone extinct.
Fortunately, most fish preserved by naturalists before 1900 were “fixed” in ethanol, which makes it easier for researchers to obtain reliable DNA than from fish preserved in a formaldehyde solution, a practice that later became popular. Prior to the new study — which included DNA from specimens up to about 150 years old — scientists working in ancient DNA labs had only performed similar research on ethanol-preserved museum vertebrate specimens less than 100 years old.
“One of the exciting things to come from this research project is that it opens up the potential for scientists to sequence the genes of other fish, reptiles and amphibian specimens preserved in ethanol further back in time than ever before to answer ecological questions about past diversity and distribution,” said Metcalf, who conducts her research at CU’s BioFrontiers Institute.
Funding for the study was provided by agencies of the Greenback Cutthroat Trout Recovery Team, including the USFWS, the U.S. Forest Service, the Bureau of Land Management, the National Park Service and Trout Unlimited.
“I think in many cases success depends less on the application of a new technology and more on the convergence of people with shared interest and complementary skills necessary for solving difficult problems,” said Martin. “Our greenback story is really one about what can be discovered when dedicated and talented people collaborate with a shared purpose.”
“We’ve known for some time that the trout in Bear Creek were unique,” said Doug Krieger, senior aquatic biologist for Colorado Parks and Wildlife and the Greenback Cutthroat Trout Recovery Team leader. “But we didn’t realize they were the only surviving greenback population.”
The decline of native cutthroats in Colorado occurred because of a combination of pollution, overfishing and stocking of native and non-native species of trout, said Metcalf. “It’s ironic that stocking nearly drove the greenback cutthroat trout to extinction, and a particularly early stocking event actually saved it from extinction,” she said.
–