Although the odds that DNA evidence found at a crime scene will match by chance the DNA of a person who was not there are infinitesimal, controversy continues about DNA identification and its use in criminal investigations, says Carnegie Mellon University Statistics Professor Kathryn Roeder. Roeder will present a historical overview of the use of DNA identification on Tuesday, April 25, during the Annual Symposia of the National Academy of Sciences in Washington, D.C.
Almost 28,000 cases nationwide have been prosecuted with help from the FBI's data bank of DNA profiles, while at least 170 people have seen their convictions overturned on appeal thanks to DNA evidence. Nonetheless, the use of DNA evidence in appeals has been impeded by political considerations and legal uncertainties, according to Roeder. "After all other legal avenues have been tried, the hope of any innocent person is that biological evidence from their cases still exists and can be subjected to DNA testing. But DNA's value to free the wrongfully convicted can be attained only if political leaders allow its full application," Roeder said. "Thousands currently await the evaluation of their cases."
In the early phases, technical disputes among scientists impeded the use of DNA evidence, Roeder said. One of the earliest controversies to erupt over DNA testing was the magnitude of genetic diversity among people of different ancestry.
Some controversy remains concerning the so-called "cold hit" technique, in which investigators search a DNA database to find a match of DNA found at a crime scene and then collect other evidence to build their case -- as opposed to first identifying a suspect through other evidence and then using DNA to confirm their case. Some critics claimed that this practice could snag an innocent person, but Roeder has demonstrated through her own research that the likelihood of a false hit are miniscule -- in one case, for example, it was about 1 in 26 quintillion, a probability so slight it needn't be shared with juries, Roeder said.
"The jury can't handle such small numbers. We would do them a service to simply tell them it matches or it doesn't match," Roeder said.
Roeder began her career as a biologist, and much of her current research is focused on using statistical tools to understand the workings of the human genome and the nature of inherited diseases. She is a member of the Bioinformatics and Statistics Genetics Group, which includes researchers in the departments of Statistics and Biological Sciences at Carnegie Mellon, and the departments of Psychiatry and Human Genetics at the University of Pittsburgh. The group's primary research goal is to develop statistical tools for finding associations between patterns of genetic variation and complex disease.
Contact: Jonathan Potts
Carnegie Mellon University
суббота, 29 октября 2011 г.
среда, 26 октября 2011 г.
Genome Connects The Dots Between Amphimedon, Animal Descendants
The simple sponge can reveal much about life on Earth. Researchers who have sequenced the genome of one Down Under inhabitant are learning just how common those roots are.
In a paper published online this week in the journal Nature, Rice University's Nicholas Putnam is among a group of scientists who have established a draft genome sequence for Amphimedon queenslandica, a sponge found off the coast of Australia. The genome is helping evolutionary biologists connect the dots as they look for DNA sequences shared by metazoans, or multicelled animals.
Sponges are an ancient group, with fossils dating back at least 650 million years. They are thought to have been the first group of animals to branch from all the others. Therefore, genes shared by sponges and other animals must have been present in the common ancestor of all metazoans. This ancestor would have evolved mechanisms to coordinate cell division, growth, specialization, adhesion and death; this suggests that early sponges already had a developmental set of tools similar to those in metazoans today, said Putnam, an assistant professor of ecology and evolutionary biology.
"What's exciting is the new things we're learning about animal evolution," said Putnam, who got involved with the project while working at the Department of Energy's Joint Genome Institute in 2006. "For example, sponges have embryos, and having the genome helps us look at how they develop and make specific connections to developmental pathways in other animals.
"It's the kind of thing that will lead to a much clearer understanding of what the very first metazoans looked like," he said.
That distant ancestor may well have looked like a sponge. For the paper, Putnam helped compare Amphimedon's draft genome with 13 other complete animal genomes, including a selection of invertebrates, as well as a choanoflagellate. The researchers wrote of a "striking conservation of gene structure and genome organization" that is common to all. "We can now say that the large-scale patterns of genome organization we've seen conserved in other animal groups come from the very root of the animal tree," Putnam said.
The challenge ahead is learning what they do. "The focus of my research is to understand whether patterns that have been around for a billion years have some particular functions -- or if they're hanging around because not enough time has gone by to erase them."
What's missing is also interesting, he said. The ancestral patterns of genome organization common to other creatures is absent from certain arthropods -- invertebrates that include the likes of centipedes and lobsters -- and nematodes. "If the missing pattern is neutral, you'd say that somewhere along the history of those groups, the rate of (evolutionary) change sped up enough to break the connection," Putnam said. "If it's functional, then somehow those groups overcame whatever constraint is on it in other lineages."
Also puzzling is that while Amphimedon shares key developmental genes with a diverse set of metazoans, its basic structure hasn't changed in 600 million years. Given the same roots, researchers wonder why it didn't evolve more radically, and they are working to identify the differences that gave rise to, say, nerve cells in other creatures but not sponges.
Unlocking the basic mechanisms of multicellularity may also help researchers understand what happens when those mechanisms go wrong and lead to cancer and autoimmune disorders.
Notes:
The paper's senior authors are Daniel Rokhsar of the University of California, Berkeley, and Bernard Degnan of the University of Queensland in Australia.
The work was funded by the Australian Research Council, the Department of Energy Joint Genome Institute, Harvey Karp, the National Science Foundation, the National Institutes of Health/National Human Genome Research Institute, the University of Queensland Postdoctoral Fellowship, the Sars International Center for Marine Molecular Biology, Deutsche Forschungsgemeinschaft, Agricultural and Natural Resources/University of California, the French National Center for Scientific Research, the Gordon and Betty Moore Foundation and Richard Melmon.
Source:
David Ruth
Rice University
In a paper published online this week in the journal Nature, Rice University's Nicholas Putnam is among a group of scientists who have established a draft genome sequence for Amphimedon queenslandica, a sponge found off the coast of Australia. The genome is helping evolutionary biologists connect the dots as they look for DNA sequences shared by metazoans, or multicelled animals.
Sponges are an ancient group, with fossils dating back at least 650 million years. They are thought to have been the first group of animals to branch from all the others. Therefore, genes shared by sponges and other animals must have been present in the common ancestor of all metazoans. This ancestor would have evolved mechanisms to coordinate cell division, growth, specialization, adhesion and death; this suggests that early sponges already had a developmental set of tools similar to those in metazoans today, said Putnam, an assistant professor of ecology and evolutionary biology.
"What's exciting is the new things we're learning about animal evolution," said Putnam, who got involved with the project while working at the Department of Energy's Joint Genome Institute in 2006. "For example, sponges have embryos, and having the genome helps us look at how they develop and make specific connections to developmental pathways in other animals.
"It's the kind of thing that will lead to a much clearer understanding of what the very first metazoans looked like," he said.
That distant ancestor may well have looked like a sponge. For the paper, Putnam helped compare Amphimedon's draft genome with 13 other complete animal genomes, including a selection of invertebrates, as well as a choanoflagellate. The researchers wrote of a "striking conservation of gene structure and genome organization" that is common to all. "We can now say that the large-scale patterns of genome organization we've seen conserved in other animal groups come from the very root of the animal tree," Putnam said.
The challenge ahead is learning what they do. "The focus of my research is to understand whether patterns that have been around for a billion years have some particular functions -- or if they're hanging around because not enough time has gone by to erase them."
What's missing is also interesting, he said. The ancestral patterns of genome organization common to other creatures is absent from certain arthropods -- invertebrates that include the likes of centipedes and lobsters -- and nematodes. "If the missing pattern is neutral, you'd say that somewhere along the history of those groups, the rate of (evolutionary) change sped up enough to break the connection," Putnam said. "If it's functional, then somehow those groups overcame whatever constraint is on it in other lineages."
Also puzzling is that while Amphimedon shares key developmental genes with a diverse set of metazoans, its basic structure hasn't changed in 600 million years. Given the same roots, researchers wonder why it didn't evolve more radically, and they are working to identify the differences that gave rise to, say, nerve cells in other creatures but not sponges.
Unlocking the basic mechanisms of multicellularity may also help researchers understand what happens when those mechanisms go wrong and lead to cancer and autoimmune disorders.
Notes:
The paper's senior authors are Daniel Rokhsar of the University of California, Berkeley, and Bernard Degnan of the University of Queensland in Australia.
The work was funded by the Australian Research Council, the Department of Energy Joint Genome Institute, Harvey Karp, the National Science Foundation, the National Institutes of Health/National Human Genome Research Institute, the University of Queensland Postdoctoral Fellowship, the Sars International Center for Marine Molecular Biology, Deutsche Forschungsgemeinschaft, Agricultural and Natural Resources/University of California, the French National Center for Scientific Research, the Gordon and Betty Moore Foundation and Richard Melmon.
Source:
David Ruth
Rice University
воскресенье, 23 октября 2011 г.
Innovative Research Grant From Stand Up To Cancer Goes To UNC Lineberger Scientist
Angelique Whitehurst, PhD, assistant professor of pharmacology and a member of UNC Lineberger Comprehensive Cancer Center, has been awarded one of 13 Innovative Research Grants from Stand Up to Cancer, the scientific partner of the American Association of Cancer Research.
The grants were announced during an event at the American Association for Cancer Research (AACR) 102nd Annual Meeting 2011.
SU2C's Innovative Research Grants Program, which made its first round of 13 grants in December 2009, was designed specifically to support work that incorporates new ideas and new approaches to solve critical problems in cancer research.
These innovative projects are characterized as "high-risk" because they challenge existing paradigms, and because in order to receive a grant, the applicants were not required - as they would be by most conventional funding mechanisms - to have already conducted a portion of the research resulting in an established base of evidence. If successful, the projects have the potential for "high-reward" in terms of saving lives.
Whitehurst will use the grant to study how genes, otherwise required only for human reproduction, contribute to tumor cell survival. She will evaluate these genes to determine which are most critical for tumor survival and how they support growth of tumor cells. Ultimately her work will present new therapeutic targets that will selectively destroy tumor cells and leave normal tissue unharmed.
Whitehurst earned her bachelor's degree in biochemistry and chemistry from Virginia Polytechnic Institute and he doctorate in cell and molecular biology from the UT Southwestern Medical Center where she also completed her postdoctoral fellowship in cell biology before joining the UNC faculty in 2009.
Source:
Dianne Shaw
University of North Carolina School of Medicine
The grants were announced during an event at the American Association for Cancer Research (AACR) 102nd Annual Meeting 2011.
SU2C's Innovative Research Grants Program, which made its first round of 13 grants in December 2009, was designed specifically to support work that incorporates new ideas and new approaches to solve critical problems in cancer research.
These innovative projects are characterized as "high-risk" because they challenge existing paradigms, and because in order to receive a grant, the applicants were not required - as they would be by most conventional funding mechanisms - to have already conducted a portion of the research resulting in an established base of evidence. If successful, the projects have the potential for "high-reward" in terms of saving lives.
Whitehurst will use the grant to study how genes, otherwise required only for human reproduction, contribute to tumor cell survival. She will evaluate these genes to determine which are most critical for tumor survival and how they support growth of tumor cells. Ultimately her work will present new therapeutic targets that will selectively destroy tumor cells and leave normal tissue unharmed.
Whitehurst earned her bachelor's degree in biochemistry and chemistry from Virginia Polytechnic Institute and he doctorate in cell and molecular biology from the UT Southwestern Medical Center where she also completed her postdoctoral fellowship in cell biology before joining the UNC faculty in 2009.
Source:
Dianne Shaw
University of North Carolina School of Medicine
четверг, 20 октября 2011 г.
Einstein Researchers Take The Pulse Of A Gene In Living Cells
Scientists at the Albert Einstein College of Medicine of Yeshiva University have observed for the first time that gene expression can occur in the form of discrete "pulses" of gene activity. The researchers used pioneering microscopy techniques, developed by Dr. Robert Singer and colleagues at Einstein, that for the first time allow scientists to directly watch the behavior of a single gene in real time. Their findings appeared in the current issue of Current Biology.
When a gene is expressed or "turned on," genetic information is transferred from DNA into RNA. This process, known as transcription, is crucial for translating the gene's message into a functional protein. Diseases such as cancer can result when genes turn on at the improper time or in the wrong part of the body.
Researchers customarily use microarrays (also known as "gene chips") to assess gene expression in tumors and other tissues. But with millions of cells involved, microarrays reflect only "average" gene expression. Just how a gene is transcribed in a single cell--continuously, intermittently or some other way--has largely been a mystery.
Now, in observing a gene that plays a major role in how an organism develops, the Einstein researchers observed a phenomenon that until now has been indirectly observed and only in bacteria: pulses of transcription that turn on and off at irregular intervals. Dr. Singer and his co-workers used a fluorescent marker that sticks to the gene only when it is active. Under a microscope, this fluorescent marker appears when the gene turns on, then disappears (gene "off") and then appears again (gene "on").
The focus of the study was a gene important in the life cycle of the social amoeba Dictyostelium, thousands of which sometimes aggregate into a single slug-like mass. This developmental gene plays a major role in transforming the "slug" into a stalk-like structure called a fruiting body, which releases new amoebae.
"The pulsing we observed in this gene would allow it to very precisely regulate development," says Dr. Singer, the study's senior author and professor and co-chair of the Department of Anatomy & Structural Biology at Einstein. He likens a gene to a thermostat:
"Heating a home all the time would be wasteful and would overheat the house," he says. "The solution is a thermostat, which injects a little bit of heat when needed and then turns off. Similarly, a cell needs the gene to be turned on--but too much activity at the wrong time can be a problem, so the solution is to have small bursts of activity."
Still to be discovered, says Dr. Singer, is how the pulsing mechanism itself is controlled. In addition, these findings pertain to developmental genes, which are turned on selectively and only in certain tissues. "Other genes--so-called constitutive genes--are regularly expressed by all the cells of an organism," Dr. Singer notes. "We'd like to find out whether these genes pulse as well."
Also involved in this study were Jonathan R. Chubb (now at University of Dundee in the U.K.), Tatjana Trcek and Shailesh M. Shenoy.
Contact: Karen Gardner
Albert Einstein College of Medicine
When a gene is expressed or "turned on," genetic information is transferred from DNA into RNA. This process, known as transcription, is crucial for translating the gene's message into a functional protein. Diseases such as cancer can result when genes turn on at the improper time or in the wrong part of the body.
Researchers customarily use microarrays (also known as "gene chips") to assess gene expression in tumors and other tissues. But with millions of cells involved, microarrays reflect only "average" gene expression. Just how a gene is transcribed in a single cell--continuously, intermittently or some other way--has largely been a mystery.
Now, in observing a gene that plays a major role in how an organism develops, the Einstein researchers observed a phenomenon that until now has been indirectly observed and only in bacteria: pulses of transcription that turn on and off at irregular intervals. Dr. Singer and his co-workers used a fluorescent marker that sticks to the gene only when it is active. Under a microscope, this fluorescent marker appears when the gene turns on, then disappears (gene "off") and then appears again (gene "on").
The focus of the study was a gene important in the life cycle of the social amoeba Dictyostelium, thousands of which sometimes aggregate into a single slug-like mass. This developmental gene plays a major role in transforming the "slug" into a stalk-like structure called a fruiting body, which releases new amoebae.
"The pulsing we observed in this gene would allow it to very precisely regulate development," says Dr. Singer, the study's senior author and professor and co-chair of the Department of Anatomy & Structural Biology at Einstein. He likens a gene to a thermostat:
"Heating a home all the time would be wasteful and would overheat the house," he says. "The solution is a thermostat, which injects a little bit of heat when needed and then turns off. Similarly, a cell needs the gene to be turned on--but too much activity at the wrong time can be a problem, so the solution is to have small bursts of activity."
Still to be discovered, says Dr. Singer, is how the pulsing mechanism itself is controlled. In addition, these findings pertain to developmental genes, which are turned on selectively and only in certain tissues. "Other genes--so-called constitutive genes--are regularly expressed by all the cells of an organism," Dr. Singer notes. "We'd like to find out whether these genes pulse as well."
Also involved in this study were Jonathan R. Chubb (now at University of Dundee in the U.K.), Tatjana Trcek and Shailesh M. Shenoy.
Contact: Karen Gardner
Albert Einstein College of Medicine
понедельник, 17 октября 2011 г.
Detection Of DNA On Nanotubes Offers New Sensing, Sequencing Technologies
Researchers at the University of Illinois at Urbana-Champaign who recently reported that DNA-wrapped carbon nanotubes could serve as sensors in living cells now say the tiny tubes can be used to target specific DNA sequences. Potential applications for the new sensors range from rapid detection of hazardous biological agents to simpler and more efficient forensic identification.
In the Jan. 27 issue of the journal Science, chemical and biomolecular engineering professor Michael Strano and his students reported that single-walled carbon nanotubes coated with DNA could be placed in living cells and detect trace amounts of harmful contaminants. In a paper accepted for publication in the journal Nano Letters, and posted on its Web site, the researchers report they have taken the technique a significant step further.
"We have successfully demonstrated the optical detection of selective DNA hybridization on the surface of a nanotube," said Strano, who is also a researcher at the Beckman Institute for Advanced Science and Technology and at the university's Micro and Nanotechnology Laboratory. "This work opens possibilities for new types of nanotube-based sensing and sequencing technologies."
In its natural state, DNA is in the double stranded form, consisting of two complementary strands, each resembling the side of a ladder and having a specific sequence of nucleotide bases as rungs. Hybridization refers to the spontaneous binding of two complementary strands through base pair matching.
By wrapping one strand of DNA around the surface of a carbon nanotube, the researchers can create a sensor that is targeted for a particular piece of complementary DNA. When the complementary DNA then binds to the DNA probe, the nanotube's natural near-infrared fluorescence is shifted slightly, and can readily be detected.
"The optical detection of specific DNA sequences through hybridization with a complementary DNA probe has many potential applications in medicine, microbiology and environmental science," said Esther Jeng, a graduate student at Illinois and the paper's lead author. "For example, this system could be used in genomic screening to detect sequences that encode for genetic disorders, and that are precursors to diseases such as breast cancer."
"Optical detection allows for passive sensing of hybridization, meaning there is no need to pass voltage or current through the system," Jeng said. "Furthermore, optics yield high-resolution signals and require a relatively simple setup. And, because our detection setup is in solution, we can sense in a natural biological environment."
Co-authors of the paper with Strano and Jeng are undergraduate students Joseph Gastala, Anthonie Moll and Amanda Roy. The work was funded by the National Science Foundation.
Contact: James E. Kloeppel, Physical Sciences Editor
kloeppeluiuc.edu
University of Illinois at Urbana-Champaign
In the Jan. 27 issue of the journal Science, chemical and biomolecular engineering professor Michael Strano and his students reported that single-walled carbon nanotubes coated with DNA could be placed in living cells and detect trace amounts of harmful contaminants. In a paper accepted for publication in the journal Nano Letters, and posted on its Web site, the researchers report they have taken the technique a significant step further.
"We have successfully demonstrated the optical detection of selective DNA hybridization on the surface of a nanotube," said Strano, who is also a researcher at the Beckman Institute for Advanced Science and Technology and at the university's Micro and Nanotechnology Laboratory. "This work opens possibilities for new types of nanotube-based sensing and sequencing technologies."
In its natural state, DNA is in the double stranded form, consisting of two complementary strands, each resembling the side of a ladder and having a specific sequence of nucleotide bases as rungs. Hybridization refers to the spontaneous binding of two complementary strands through base pair matching.
By wrapping one strand of DNA around the surface of a carbon nanotube, the researchers can create a sensor that is targeted for a particular piece of complementary DNA. When the complementary DNA then binds to the DNA probe, the nanotube's natural near-infrared fluorescence is shifted slightly, and can readily be detected.
"The optical detection of specific DNA sequences through hybridization with a complementary DNA probe has many potential applications in medicine, microbiology and environmental science," said Esther Jeng, a graduate student at Illinois and the paper's lead author. "For example, this system could be used in genomic screening to detect sequences that encode for genetic disorders, and that are precursors to diseases such as breast cancer."
"Optical detection allows for passive sensing of hybridization, meaning there is no need to pass voltage or current through the system," Jeng said. "Furthermore, optics yield high-resolution signals and require a relatively simple setup. And, because our detection setup is in solution, we can sense in a natural biological environment."
Co-authors of the paper with Strano and Jeng are undergraduate students Joseph Gastala, Anthonie Moll and Amanda Roy. The work was funded by the National Science Foundation.
Contact: James E. Kloeppel, Physical Sciences Editor
kloeppeluiuc.edu
University of Illinois at Urbana-Champaign
пятница, 14 октября 2011 г.
Deciphering The Metabolism Of Sexual Assault Drug
It's a naturally occurring brain chemical with an unwieldy name: 4-hydroxybutyrate (4-HB). Taken by mouth, it can be abused or used as a date-rape drug.
Now, a team of Ohio and Michigan scientists have determined new routes by which 4-HB is metabolized by the body. "This is new and important information," said K. Michael Gibson, professor and chair of biological sciences at Michigan Technological University and a member of the research team. "It may provide new clues on how to counteract the drug's effects, or to enhance its metabolism and decrease toxicity for chronic abusers or victims of sexual assault."
Gibson is co-author with Guo-Fang Zhang and others in the laboratory of Prof. Henri Brunengraber from the Department of Nutrition at Case Western Reserve University School of Medicine of a paper published online by the Journal of Biological Chemistry. Their findings will appear in as "paper of the week" in the the print edition of the weekly journal on Nov. 27, 2009.
4-HB is a derivative of a major brain neurotransmitter in humans and other species. . It occurs naturally in small amounts in the brains of most animals and humans. In a rare genetic metabolic disorder, 4-HB accumulates in extremely high levels, causing significant developmental delays and seizures.
But 4-HB - also called gamma hydroxybutyrate or GHB - is best known and most feared when it is taken orally, because it is a drug that impairs the capacity to exercise judgment, like rohypnol and ketamine hydrochloride. For that reason, it can be used to facilitate acquaintance sexual assault, commonly called date rape.
Analyzing the chemicals produced by the breakdown of 4-HB in mice and rats, Zhang, Gibson and colleagues used very sophisticated mass spectrometry approaches to identify previously unknown enzymes and pathways that appear to act on 4-HB and other similarly structured compounds. They discovered that 4-HB is metabolized by two different chemical mechanisms or pathways. Their discovery of those pathways should open the door for future studies that can identify the enzymes involved in the following steps of the breakdown of 4-HB.
"This work may help to develop new antidotes and treatments for people who have ingested 4-HB, as well as treatment for children with the rare genetic disorder that causes the compound to accumulate in high levels," Gibson said. (For more information on genetic disorders of 4-HB, see pndassoc)
Source: Jennifer Donovan
Michigan Technological University
Now, a team of Ohio and Michigan scientists have determined new routes by which 4-HB is metabolized by the body. "This is new and important information," said K. Michael Gibson, professor and chair of biological sciences at Michigan Technological University and a member of the research team. "It may provide new clues on how to counteract the drug's effects, or to enhance its metabolism and decrease toxicity for chronic abusers or victims of sexual assault."
Gibson is co-author with Guo-Fang Zhang and others in the laboratory of Prof. Henri Brunengraber from the Department of Nutrition at Case Western Reserve University School of Medicine of a paper published online by the Journal of Biological Chemistry. Their findings will appear in as "paper of the week" in the the print edition of the weekly journal on Nov. 27, 2009.
4-HB is a derivative of a major brain neurotransmitter in humans and other species. . It occurs naturally in small amounts in the brains of most animals and humans. In a rare genetic metabolic disorder, 4-HB accumulates in extremely high levels, causing significant developmental delays and seizures.
But 4-HB - also called gamma hydroxybutyrate or GHB - is best known and most feared when it is taken orally, because it is a drug that impairs the capacity to exercise judgment, like rohypnol and ketamine hydrochloride. For that reason, it can be used to facilitate acquaintance sexual assault, commonly called date rape.
Analyzing the chemicals produced by the breakdown of 4-HB in mice and rats, Zhang, Gibson and colleagues used very sophisticated mass spectrometry approaches to identify previously unknown enzymes and pathways that appear to act on 4-HB and other similarly structured compounds. They discovered that 4-HB is metabolized by two different chemical mechanisms or pathways. Their discovery of those pathways should open the door for future studies that can identify the enzymes involved in the following steps of the breakdown of 4-HB.
"This work may help to develop new antidotes and treatments for people who have ingested 4-HB, as well as treatment for children with the rare genetic disorder that causes the compound to accumulate in high levels," Gibson said. (For more information on genetic disorders of 4-HB, see pndassoc)
Source: Jennifer Donovan
Michigan Technological University
вторник, 11 октября 2011 г.
Research To Examine Connection Between Cancer, Genetics Among American Indians
The Montana Cancer Institute Foundation and the Confederated Salish and Kootenai Tribal Health Department are collaborating on a new program to determine whether American Indians possess certain genetic traits that could fight cancer or make them respond less effectively to cancer treatments, the Lake County Leader & Advertiser reports.
American Indians coming to Tribal Health for regular appointments will be able to donate blood to the research. Participants each will be given $10 for donating. MCIF President Pat Beatty said that the goal is to collect blood from 1,000 local American Indians. Researchers at the University of Rochester will examine the blood samples to look for nine specific genetic markers. Beatty said similar testing has been conducted among other populations. According to Beatty, "Nobody has ever studied this systematically in Native Americans."
Research among American Indians has been difficult because of a lack of research institutions in areas with large American Indian populations. In addition, American Indians are often resistant to "outsiders performing research experiments," the Leader & Advertiser reports. Beatty said, "Many Native Americans, for good reason, don't have a lot of trust in the medical system. So that means that it's almost impossible for some unknown research project to come out and do something like this." The research project is being run through Tribal Health to help gain participants' trust, the Leader & Advertiser reports (McBride, Lake County Leader & Advertiser, 2/7).
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
American Indians coming to Tribal Health for regular appointments will be able to donate blood to the research. Participants each will be given $10 for donating. MCIF President Pat Beatty said that the goal is to collect blood from 1,000 local American Indians. Researchers at the University of Rochester will examine the blood samples to look for nine specific genetic markers. Beatty said similar testing has been conducted among other populations. According to Beatty, "Nobody has ever studied this systematically in Native Americans."
Research among American Indians has been difficult because of a lack of research institutions in areas with large American Indian populations. In addition, American Indians are often resistant to "outsiders performing research experiments," the Leader & Advertiser reports. Beatty said, "Many Native Americans, for good reason, don't have a lot of trust in the medical system. So that means that it's almost impossible for some unknown research project to come out and do something like this." The research project is being run through Tribal Health to help gain participants' trust, the Leader & Advertiser reports (McBride, Lake County Leader & Advertiser, 2/7).
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
суббота, 8 октября 2011 г.
New Test Helps Identify Hepatitis C Patients At High Risk Of Developing Cirrhosis
A researcher at the Stanford University School of Medicine has helped confirm the reliability of a new test for liver disease that is ushering in the long-promised era of personalized medicine based on each individual's genetic makeup.
The Stanford group was one of the five sites that helped determine that the genetic test can identify patients who are at high risk of developing cirrhosis from chronic hepatitis C infection. That means high-risk patients could be directed toward a long course of expensive, debilitating drug therapy, while low-risk patients might be better off delaying treatment.
"Management of cirrhosis patients is challenging," said Ramsey Cheung, MD, associate professor of medicine at the school and chief of hepatology at the Palo Alto Veterans Affairs Health Care System, who led the Stanford arm of the study. "This test is the first of its kind to use the genetic makeup of each patient to determine who is likely to develop cirrhosis. High-risk patients should be targeted for early treatment."
The test looks at variations of seven genes, and was developed by Celera, headquartered in Rockville, Md.
Cheung is the senior author of the study, which will be published in the advance online issue of the journal Hepatology. Cheung is a paid consultant for Celera, which also funded the study.
"Current therapy for hepatitis C unfortunately is very expensive, has multiple side effects and a suboptimal response rate for most patients," said Cheung. Treatment includes weekly injections of alpha interferon along with the drug ribavirin, which can cost more than $30,000 per year and can cause flu-like symptoms, nausea, depression and other side effects. And only half of patients undergoing this therapy will be cured of the infection.
Nearly 4 million Americans are infected with the hepatitis C virus, of which nearly 80 percent have a chronic infection, according to the American Liver Foundation. Chronic infection can lead to the severe scarring known as cirrhosis, which in turn may result in liver cancer or liver failure. Hepatitis C infection is the most common reason people need a liver transplant in the United States and is responsible for between 8,000 and 10,000 U.S. deaths annually.
But in the majority of people chronically infected with hepatitis C, the virus causes either no symptoms or vague, nonspecific ones. In around one-third of people chronically infected with the virus, the disease progression is slow and they may never develop cirrhosis, even after decades of infection.
The dilemma physicians face, explained Cheung, is deciding who to treat and who can wait for better therapies to come along. The key is being able to determine which patients are likely to see the infection progress to cirrhosis. Doctors consider such factors as age, gender and alcohol consumption to predict such risk, but because of individual variability, these factors don't yield a very accurate prediction. A liver biopsy can indicate the amount of damage to the liver up until the time of the biopsy, but can't reveal how much future damage will occur.
The new test assessed by Cheung and his colleagues is a way to hedge the bets.
The lead author of the paper is Hongjin Huang, PhD, associate director of liver diseases at Celera in Alameda, Calif. Huang and her Celera colleagues developed the test by initially scanning the DNA of more than 1,000 people who had hepatitis C. Out of 25,000 genetic variations tested, the researchers discovered seven that could be used together as a "signature" for predicting progression to cirrhosis in Caucasians.
The resulting gene signature - the Cirrhosis Risk Score - was then independently validated on 154 hepatitis C patients at Stanford, the University of Illinois-Chicago and California Pacific Medical Center. Among patients with early-stage liver disease, the researchers were able to divide them into a high-risk category based on their gene pattern, compared with those who had low-risk gene patterns. "The Cirrhosis Risk Score was superior to the known clinical factors, such as alcohol consumption, in predicting the risk of developing cirrhosis," said Cheung.
"This test allows both physicians and patients to make an intelligent decision about the urgency of beginning antiviral therapy," he said. "If a patient turns out to be low-risk, we might advise the patient to consider deferring treatment, avoiding unnecessary side effects and expense of current therapy."
Last June, Celera licensed Specialty Laboratories of Valencia, Calif., to perform the genetic test. The test currently costs about $500.
In addition to Cheung and Huang, the other 12 authors of the study are from Celera, Virginia Commonwealth University, Mount Sinai School of Medicine, California Pacific Medical Center, the University of Illinois-Chicago and the University of California-San Francisco.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford.edu/.
Contact: Mitzi Baker
Stanford University Medical Center
The Stanford group was one of the five sites that helped determine that the genetic test can identify patients who are at high risk of developing cirrhosis from chronic hepatitis C infection. That means high-risk patients could be directed toward a long course of expensive, debilitating drug therapy, while low-risk patients might be better off delaying treatment.
"Management of cirrhosis patients is challenging," said Ramsey Cheung, MD, associate professor of medicine at the school and chief of hepatology at the Palo Alto Veterans Affairs Health Care System, who led the Stanford arm of the study. "This test is the first of its kind to use the genetic makeup of each patient to determine who is likely to develop cirrhosis. High-risk patients should be targeted for early treatment."
The test looks at variations of seven genes, and was developed by Celera, headquartered in Rockville, Md.
Cheung is the senior author of the study, which will be published in the advance online issue of the journal Hepatology. Cheung is a paid consultant for Celera, which also funded the study.
"Current therapy for hepatitis C unfortunately is very expensive, has multiple side effects and a suboptimal response rate for most patients," said Cheung. Treatment includes weekly injections of alpha interferon along with the drug ribavirin, which can cost more than $30,000 per year and can cause flu-like symptoms, nausea, depression and other side effects. And only half of patients undergoing this therapy will be cured of the infection.
Nearly 4 million Americans are infected with the hepatitis C virus, of which nearly 80 percent have a chronic infection, according to the American Liver Foundation. Chronic infection can lead to the severe scarring known as cirrhosis, which in turn may result in liver cancer or liver failure. Hepatitis C infection is the most common reason people need a liver transplant in the United States and is responsible for between 8,000 and 10,000 U.S. deaths annually.
But in the majority of people chronically infected with hepatitis C, the virus causes either no symptoms or vague, nonspecific ones. In around one-third of people chronically infected with the virus, the disease progression is slow and they may never develop cirrhosis, even after decades of infection.
The dilemma physicians face, explained Cheung, is deciding who to treat and who can wait for better therapies to come along. The key is being able to determine which patients are likely to see the infection progress to cirrhosis. Doctors consider such factors as age, gender and alcohol consumption to predict such risk, but because of individual variability, these factors don't yield a very accurate prediction. A liver biopsy can indicate the amount of damage to the liver up until the time of the biopsy, but can't reveal how much future damage will occur.
The new test assessed by Cheung and his colleagues is a way to hedge the bets.
The lead author of the paper is Hongjin Huang, PhD, associate director of liver diseases at Celera in Alameda, Calif. Huang and her Celera colleagues developed the test by initially scanning the DNA of more than 1,000 people who had hepatitis C. Out of 25,000 genetic variations tested, the researchers discovered seven that could be used together as a "signature" for predicting progression to cirrhosis in Caucasians.
The resulting gene signature - the Cirrhosis Risk Score - was then independently validated on 154 hepatitis C patients at Stanford, the University of Illinois-Chicago and California Pacific Medical Center. Among patients with early-stage liver disease, the researchers were able to divide them into a high-risk category based on their gene pattern, compared with those who had low-risk gene patterns. "The Cirrhosis Risk Score was superior to the known clinical factors, such as alcohol consumption, in predicting the risk of developing cirrhosis," said Cheung.
"This test allows both physicians and patients to make an intelligent decision about the urgency of beginning antiviral therapy," he said. "If a patient turns out to be low-risk, we might advise the patient to consider deferring treatment, avoiding unnecessary side effects and expense of current therapy."
Last June, Celera licensed Specialty Laboratories of Valencia, Calif., to perform the genetic test. The test currently costs about $500.
In addition to Cheung and Huang, the other 12 authors of the study are from Celera, Virginia Commonwealth University, Mount Sinai School of Medicine, California Pacific Medical Center, the University of Illinois-Chicago and the University of California-San Francisco.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford.edu/.
Contact: Mitzi Baker
Stanford University Medical Center
среда, 5 октября 2011 г.
New Scenario For First Life On Earth
A team led by the University of Colorado at Boulder and the University of Milan has discovered some unexpected forms of liquid crystals of ultrashort DNA molecules immersed in water, providing a new scenario for a key step in the emergence of life on Earth.
CU-Boulder physics Professor Noel Clark said the team found that surprisingly short segments of DNA, life's molecular carrier of genetic information, could assemble into several distinct liquid crystal phases that "self-orient" parallel to one another and stack into columns when placed in a water solution. Life is widely believed to have emerged as segments of DNA- or RNA-like molecules in a prebiotic "soup" solution of ancient organic molecules.
A paper on the subject was published in the Nov. 23 issue of Science. The paper was authored by Clark, Michi Nakata and Christopher Jones from CU-Boulder, Giuliano Zanchetta and Tommaso Bellini of the University of Milan, Brandon Chapman and Ronald Pindak of Brookhaven National Laboratory and Julie Cross of Argonne National Laboratory. Nakata died in September 2006.
Since the formation of molecular chains as uniform as DNA by random chemistry is essentially impossible, Clark said, scientists have been seeking effective ways for simple molecules to spontaneously self-select, "chain-up" and self-replicate. The new study shows that in a mixture of tiny fragments of DNA, those molecules capable of forming liquid crystals selectively condense into droplets in which conditions are favorable for them to be chemically linked into longer molecules with enhanced liquid crystal-forming tendencies, he said.
"We found that even tiny fragments of double helix DNA can spontaneously self-assemble into columns that contain many molecules," Clark said. "Our vision is that from the collection of ancient molecules, short RNA pieces or some structurally related precursor emerged as the molecular fragments most capable of condensing into liquid crystal droplets, selectively developing into long molecules."
Liquid crystals -- organic materials related to soap that exhibit both solid and liquid properties -- are commonly used for information displays in computers, flat-panel televisions, cell phones, calculators and watches. Most liquid crystal phase molecules are rod-shaped and have the ability to spontaneously form large domains of a common orientation, which makes them particularly sensitive to stimuli like changes in temperature or applied voltage.
RNA and DNA are chain-like polymers with side groups known as nucleotides, or bases, that selectively adhere only to specific bases on a second chain. Matching, or complementary base sequences enable the chains to pair up and form the widely recognized double helix structure. Genetic information is encoded in sequences of thousands to millions of bases along the chains, which can be microns to millimeters in length.
Such DNA polynucleotides had previously been shown to organize into liquid crystal phases in which the chains spontaneously oriented parallel to each other, he said. Researchers understand the liquid crystal organization to be a result of DNA's elongated molecular shape, making parallel alignment easier, much like spaghetti thrown in a box and shaken would be prone to line up in parallel, Clark said.
The CU-Boulder and University of Milan team began a series of experiments to see how short the DNA segments could be and still show liquid crystal ordering, said Clark. The team found that even a DNA segment as short as six bases, when paired with a complementary segment that together measured just two nanometers long and two nanometers in diameter, could still assemble itself into the liquid crystal phases, in spite of having almost no elongation in shape.
Structural analysis of the liquid crystal phases showed that they appeared because such short DNA duplex pairs were able to stick together "end-to-end," forming rod-shaped aggregates that could then behave like much longer segments of DNA. The sticking was a result of small, oily patches found on the ends of the short DNA segments that help them adhere to each other in a reversible way -- much like magnetic buttons -- as they expelled water in between them, Clark said.
A key characterization technique employed was X-ray microbeam diffraction combined with in-situ optical microscopy, carried out with researchers from Argonne and Brookhaven National Laboratories. The team using a machine called the Argonne Advanced Photon Source synchrotron that enabled probing of the "nano DNA" molecular organization in single liquid crystal orientation domains only a few microns in size. The experiments provided direct evidence for the columnar stacking of the nano DNA pieces in a fluid liquid crystal phase.
"The key observation with respect to early life is that this aggregation of nano DNA strands is possible only if they form duplexes," Clark said. "In a sample of chains in which the bases don't match and the chains can't form helical duplexes, we did not observe liquid crystal ordering."
Subsequent tests by the team involved mixed solutions of complementary and noncomplementary DNA segments, said Clark. The results indicated that essentially all of the complementary DNA bits condensed out in the form of liquid crystal droplets, physically separating them from the noncomplementary DNA segments.
"We found this to be a remarkable result," Clark said. "It means that small molecules with the ability to pair up the right way can seek each other out and collect together into drops that are internally self-organized to facilitate the growth of larger pairable molecules.
"In essence, the liquid crystal phase condensation selects the appropriate molecular components, and with the right chemistry would evolve larger molecules tuned to stabilize the liquid crystal phase. If this is correct, the linear polymer shape of DNA itself is a vestige of formation by liquid crystal order."
Source: Noel Clark
University of Colorado at Boulder
CU-Boulder physics Professor Noel Clark said the team found that surprisingly short segments of DNA, life's molecular carrier of genetic information, could assemble into several distinct liquid crystal phases that "self-orient" parallel to one another and stack into columns when placed in a water solution. Life is widely believed to have emerged as segments of DNA- or RNA-like molecules in a prebiotic "soup" solution of ancient organic molecules.
A paper on the subject was published in the Nov. 23 issue of Science. The paper was authored by Clark, Michi Nakata and Christopher Jones from CU-Boulder, Giuliano Zanchetta and Tommaso Bellini of the University of Milan, Brandon Chapman and Ronald Pindak of Brookhaven National Laboratory and Julie Cross of Argonne National Laboratory. Nakata died in September 2006.
Since the formation of molecular chains as uniform as DNA by random chemistry is essentially impossible, Clark said, scientists have been seeking effective ways for simple molecules to spontaneously self-select, "chain-up" and self-replicate. The new study shows that in a mixture of tiny fragments of DNA, those molecules capable of forming liquid crystals selectively condense into droplets in which conditions are favorable for them to be chemically linked into longer molecules with enhanced liquid crystal-forming tendencies, he said.
"We found that even tiny fragments of double helix DNA can spontaneously self-assemble into columns that contain many molecules," Clark said. "Our vision is that from the collection of ancient molecules, short RNA pieces or some structurally related precursor emerged as the molecular fragments most capable of condensing into liquid crystal droplets, selectively developing into long molecules."
Liquid crystals -- organic materials related to soap that exhibit both solid and liquid properties -- are commonly used for information displays in computers, flat-panel televisions, cell phones, calculators and watches. Most liquid crystal phase molecules are rod-shaped and have the ability to spontaneously form large domains of a common orientation, which makes them particularly sensitive to stimuli like changes in temperature or applied voltage.
RNA and DNA are chain-like polymers with side groups known as nucleotides, or bases, that selectively adhere only to specific bases on a second chain. Matching, or complementary base sequences enable the chains to pair up and form the widely recognized double helix structure. Genetic information is encoded in sequences of thousands to millions of bases along the chains, which can be microns to millimeters in length.
Such DNA polynucleotides had previously been shown to organize into liquid crystal phases in which the chains spontaneously oriented parallel to each other, he said. Researchers understand the liquid crystal organization to be a result of DNA's elongated molecular shape, making parallel alignment easier, much like spaghetti thrown in a box and shaken would be prone to line up in parallel, Clark said.
The CU-Boulder and University of Milan team began a series of experiments to see how short the DNA segments could be and still show liquid crystal ordering, said Clark. The team found that even a DNA segment as short as six bases, when paired with a complementary segment that together measured just two nanometers long and two nanometers in diameter, could still assemble itself into the liquid crystal phases, in spite of having almost no elongation in shape.
Structural analysis of the liquid crystal phases showed that they appeared because such short DNA duplex pairs were able to stick together "end-to-end," forming rod-shaped aggregates that could then behave like much longer segments of DNA. The sticking was a result of small, oily patches found on the ends of the short DNA segments that help them adhere to each other in a reversible way -- much like magnetic buttons -- as they expelled water in between them, Clark said.
A key characterization technique employed was X-ray microbeam diffraction combined with in-situ optical microscopy, carried out with researchers from Argonne and Brookhaven National Laboratories. The team using a machine called the Argonne Advanced Photon Source synchrotron that enabled probing of the "nano DNA" molecular organization in single liquid crystal orientation domains only a few microns in size. The experiments provided direct evidence for the columnar stacking of the nano DNA pieces in a fluid liquid crystal phase.
"The key observation with respect to early life is that this aggregation of nano DNA strands is possible only if they form duplexes," Clark said. "In a sample of chains in which the bases don't match and the chains can't form helical duplexes, we did not observe liquid crystal ordering."
Subsequent tests by the team involved mixed solutions of complementary and noncomplementary DNA segments, said Clark. The results indicated that essentially all of the complementary DNA bits condensed out in the form of liquid crystal droplets, physically separating them from the noncomplementary DNA segments.
"We found this to be a remarkable result," Clark said. "It means that small molecules with the ability to pair up the right way can seek each other out and collect together into drops that are internally self-organized to facilitate the growth of larger pairable molecules.
"In essence, the liquid crystal phase condensation selects the appropriate molecular components, and with the right chemistry would evolve larger molecules tuned to stabilize the liquid crystal phase. If this is correct, the linear polymer shape of DNA itself is a vestige of formation by liquid crystal order."
Source: Noel Clark
University of Colorado at Boulder
воскресенье, 2 октября 2011 г.
Missing Evolutionary Link Found Using Tiny Fungus Crystal
The crystal structure of a molecule from a primitive fungus has served as a time machine to show researchers more about the evolution of life from the simple to the complex.
By studying the three-dimensional version of the fungus protein bound to an RNA molecule, scientists from Purdue University and the University of Texas at Austin have been able to visualize how life progressed from an early self-replicating molecule that also performed chemical reactions to one in which proteins assumed some of the work.
"Now we can see how RNA progressed to share functions with proteins," said Alan Lambowitz, director of the University of Texas Institute for Cellular and Molecular Biology. "This was a critical missing step."
Results of the study are published in today's (Jan. 3) issue of the journal Nature.
"It's thought that RNA, or a molecule like it, may have been among the first molecules of life, both carrying genetic code that can be transmitted from generation to generation and folding into structures so these molecules could work inside cells," said Purdue structural biologist Barbara Golden. "At some point, RNA evolved and became capable of making proteins. At that point, proteins started taking over roles that RNA played previously - acting as catalysts and building structures in cells."
In order to show this and learn more about the evolution from RNA to more complex life forms, Lambowitz and Paul Paukstelis, lead author and a research scientist at the Texas institute, needed to be able to see how the fungus' protein worked. That's where Golden's team joined the effort and crystallized the molecule at Purdue's macromolecular crystallization facility.
"Obviously, we can't see the process of moving from RNA to RNA and proteins and then to DNA, without a time machine," Golden said. "But by using this fungus protein, we can see this process occurring in modern life."
Looking at the crystal, the scientists saw two things, Golden said. One was that this protein uses two completely different molecular surfaces to perform its two roles. The second is that the protein seems to perform the same job that RNA performed in other simple organisms.
"The crystal structure provides a snapshot of how, during evolution, protein molecules came to assist RNA molecules in their biological functions and ultimately assumed roles previously played by RNA," Golden said.
Before the crystallization, Lambowitz, Paukstelis and their research team at The University of Texas at Austin were involved in a long-term project to study the function of the basic cellular workhorse protein and other evolutionary fossils from the fungus. In earlier work, the scientists studied a different protein that showed how biochemical processes could progress from a world with RNA and protein to DNA.
The protein, as found in the fungus, had adapted to take over some of the RNA molecule's chemical reaction jobs inside cells. The protein stabilizes the RNA molecule - called an intron - so that the RNA can cut out non-functional genetic material and splice together the ends of a functional gene, Paukstelis said.
"The RNA molecule in our study is capable of performing a specific chemical reaction on itself, but it requires a protein for this reaction to take place efficiently," he said.
This basic scientific information eventually could lead to clinical applications.
"This work has potential applications in the development of antifungal drugs to battle potentially deadly pathogens; that's one of the next steps," Lambowitz said. "Another is to produce more detailed structures so that we can understand the ancient chemical reactions."
Golden and Lambowitz are senior authors of the report. Golden is a member of the Markey Center for Structural Biology and Purdue Cancer Center. The Markey Center will be housed in the Hockmeyer Hall of Structural Biology when it's completed on the West Lafayette campus.
Other researchers involved in this study along with Paukstelis were Jui-Hui Chen, a Purdue biochemistry doctoral student, and Elaine Chase, a Purdue biochemistry research technician.
Source: Susan A. Steeves
Purdue University
By studying the three-dimensional version of the fungus protein bound to an RNA molecule, scientists from Purdue University and the University of Texas at Austin have been able to visualize how life progressed from an early self-replicating molecule that also performed chemical reactions to one in which proteins assumed some of the work.
"Now we can see how RNA progressed to share functions with proteins," said Alan Lambowitz, director of the University of Texas Institute for Cellular and Molecular Biology. "This was a critical missing step."
Results of the study are published in today's (Jan. 3) issue of the journal Nature.
"It's thought that RNA, or a molecule like it, may have been among the first molecules of life, both carrying genetic code that can be transmitted from generation to generation and folding into structures so these molecules could work inside cells," said Purdue structural biologist Barbara Golden. "At some point, RNA evolved and became capable of making proteins. At that point, proteins started taking over roles that RNA played previously - acting as catalysts and building structures in cells."
In order to show this and learn more about the evolution from RNA to more complex life forms, Lambowitz and Paul Paukstelis, lead author and a research scientist at the Texas institute, needed to be able to see how the fungus' protein worked. That's where Golden's team joined the effort and crystallized the molecule at Purdue's macromolecular crystallization facility.
"Obviously, we can't see the process of moving from RNA to RNA and proteins and then to DNA, without a time machine," Golden said. "But by using this fungus protein, we can see this process occurring in modern life."
Looking at the crystal, the scientists saw two things, Golden said. One was that this protein uses two completely different molecular surfaces to perform its two roles. The second is that the protein seems to perform the same job that RNA performed in other simple organisms.
"The crystal structure provides a snapshot of how, during evolution, protein molecules came to assist RNA molecules in their biological functions and ultimately assumed roles previously played by RNA," Golden said.
Before the crystallization, Lambowitz, Paukstelis and their research team at The University of Texas at Austin were involved in a long-term project to study the function of the basic cellular workhorse protein and other evolutionary fossils from the fungus. In earlier work, the scientists studied a different protein that showed how biochemical processes could progress from a world with RNA and protein to DNA.
The protein, as found in the fungus, had adapted to take over some of the RNA molecule's chemical reaction jobs inside cells. The protein stabilizes the RNA molecule - called an intron - so that the RNA can cut out non-functional genetic material and splice together the ends of a functional gene, Paukstelis said.
"The RNA molecule in our study is capable of performing a specific chemical reaction on itself, but it requires a protein for this reaction to take place efficiently," he said.
This basic scientific information eventually could lead to clinical applications.
"This work has potential applications in the development of antifungal drugs to battle potentially deadly pathogens; that's one of the next steps," Lambowitz said. "Another is to produce more detailed structures so that we can understand the ancient chemical reactions."
Golden and Lambowitz are senior authors of the report. Golden is a member of the Markey Center for Structural Biology and Purdue Cancer Center. The Markey Center will be housed in the Hockmeyer Hall of Structural Biology when it's completed on the West Lafayette campus.
Other researchers involved in this study along with Paukstelis were Jui-Hui Chen, a Purdue biochemistry doctoral student, and Elaine Chase, a Purdue biochemistry research technician.
Source: Susan A. Steeves
Purdue University
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