Microbes matter -- perhaps more than anyone realizes -- in basic biological development and, maybe, they could be a target for reducing cancer risks, according to University of Oregon researchers.
In a study of very basic biology of zebrafish, scientists in the UO Institute of Molecular Biology focused on the developing intestine during its early formation in the sterile environment of its eggshell through the exposure to natural colonizing bacteria after hatching.
What they found was eye opening, said Karen Guillemin, professor of biology: Resident microbes in the still-maturing intestine send messages that promote non-disease-related cell proliferation in the same Wnt [pronounced went] signaling pathway where genetic mutations have long been known to give rise to colorectal cancer. The findings appeared online ahead of regular publication in the Proceedings of the National Academy of Sciences.
The complex Wnt pathway in the gut already is considered the starting point for more than 70 percent of sporadic colorectal cancers. In the study, researchers used normal zebrafish and those harboring mutations in the Wnt pathway. They were reared under germ-free conditions and then exposed under laboratory conditions to specific microbes to define how microbial signals interact with the Wnt pathway to promote cell proliferation in the gut.
"We were able to show that microbial signals do feed into and enhance signaling in the Wnt pathway. They feed in at a point after the node where most cancer-promoting genetic mutations occur," Guillemin said. "What this says is that for anyone who is at risk for developing cancer because they have these mutations, it matters what microbes these mutations are associated with. These two pieces of information contribute in parallel and feed into the same pathway."
The findings, she said, add fodder in an emerging shift in cancer research to look at the impact of microbes and other infectious causes of the disease. "It may be that associated microbes play as significant a role in cancer risk as genetic mutations," she said. "We need to learn more about the contributions of microbe signaling to cell proliferation. Maybe you could intervene with a targeted therapy. Even if you can't fix a mutation you might manipulate the associated microbes to change the interaction and reduce unwanted cell proliferation."
Genetic research on zebrafish - a high-priority model organism for the National Institutes of Health, which supported the project - began at the UO in the early 1970s. Guillemin, who recently received an early career investigator-scholar award from the NIH Institute of Digestive and Kidney Diseases, is known for her studies in zebrafish on the role of good bacteria in the gastrointestinal tract.
Notes:
Co-authors on the paper were Sarah E. Cheesman, who was supported by an NIH Research Service Award fellowship, doctoral student James T. Neal and research technicians Erika Mittge and Barbara M. Seredick.
In addition to the NIH, the Burroughs Wellcome Fund supported the research.
Source:
Jim Barlow
University of Oregon
четверг, 29 сентября 2011 г.
понедельник, 26 сентября 2011 г.
Drug That Switches On Genes Improves Myelodysplastic Syndrome Treatment
A potent member of a new class of drugs increases survival in some patients with myelodysplastic syndrome (MDS), and may become the new standard of therapy for this group of pre-cancer disorders, say researchers at The University of Texas M. D. Anderson Cancer Center who led a national study of the agent.
The drug, decitabine, is designed to turn on genes that cancer had switched off, and in this study, patients who were treated with it achieved a significantly higher overall response rate, compared to patients receiving supportive care, which includes transfusions of red blood cells and platelets.
Results of the randomized Phase III clinical trial, published March 13, 2006 in the online version of the journal Cancer, also concluded that in treated patients who responded to the drug, the median time to progression of the disease, or death, was 17.5 months, compared to 9.8 months in patients who did not.
"This is a very promising drug that we believe works even better when patients use it for a period that is longer than that tested in this trial," says lead author, Hagop Kantarjian, M.D., chair of the Department of Leukemia at M. D. Anderson.
For example, interim analysis of an ongoing study demonstrated a 40 percent complete response rate when the drug was given in lower doses over a longer period of time, said Kantarjian, who presented these results in December 2005, at the annual meeting of the American Society of Hematology. In contrast, the 83 patients treated with decitabine in this study received comparatively fewer rounds of therapy, and the response rate was 17 percent, he said.
"The data suggest to us that prolonged treatment is important for response but the optimal schedule for using decitabine is being studied," said Kantarjian.
Still, he says a significant response rate represents "a vast improvement" in the care of these pre-cancers, which are a group of diseases in which the bone marrow progenitor cells that normally morph into red and white blood cells and platelets, fail to respond to normal growth controls. That results in too many progenitor cells (also known as blasts) and too few mature blood cells, and in about 30 percent of patients, the disease progresses to acute myeloid leukemia (AML). About three-fourths of MDS patients succumb to either MDS or to AML within about 2-3 years from diagnosis.
MDS is difficult to treat, especially since it usually strikes the elderly. Ten years ago, there was little to offer patients other than blood transfusions and supportive care, Kantarjian says, and newer treatments, which include the use of stem cell transplants, are not for every patient.
Decitabine is a "biological disease modifier" that was given fast-track approval by the Food and Drug Administration in April 2003.
It is a DNA hypomethylating agent that fights cancer by reversing a chemical process (methylation) that turns off tumor-suppressor genes that protect cells from becoming cancerous. Methylation is the gradual addition of chemical units known as methyl groups to genes, and as these groups accumulate, the gene gradually shuts down. Decitabine prevents the methylation process, enabling the gene to become active again.
In addition to increased survival and time-to-progression in some patients, decitabine improved quality of life in patients who responded and eliminated the need for frequent transfusions, Kantarjian said.
Other institutions that participated in the study were The University of Rochester Medical Center, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Roswell Park Cancer Institute, Duke University Medical Center, University of Illinois, Southwest Regional Cancer Center, Rush Medical Center, and H. Lee Moffitt Cancer Center.
The study was funded by Supergen Inc., which developed decitabine.
Contact: Julie A. Penne
jpennemdanderson
University of Texas M. D. Anderson Cancer Center
The drug, decitabine, is designed to turn on genes that cancer had switched off, and in this study, patients who were treated with it achieved a significantly higher overall response rate, compared to patients receiving supportive care, which includes transfusions of red blood cells and platelets.
Results of the randomized Phase III clinical trial, published March 13, 2006 in the online version of the journal Cancer, also concluded that in treated patients who responded to the drug, the median time to progression of the disease, or death, was 17.5 months, compared to 9.8 months in patients who did not.
"This is a very promising drug that we believe works even better when patients use it for a period that is longer than that tested in this trial," says lead author, Hagop Kantarjian, M.D., chair of the Department of Leukemia at M. D. Anderson.
For example, interim analysis of an ongoing study demonstrated a 40 percent complete response rate when the drug was given in lower doses over a longer period of time, said Kantarjian, who presented these results in December 2005, at the annual meeting of the American Society of Hematology. In contrast, the 83 patients treated with decitabine in this study received comparatively fewer rounds of therapy, and the response rate was 17 percent, he said.
"The data suggest to us that prolonged treatment is important for response but the optimal schedule for using decitabine is being studied," said Kantarjian.
Still, he says a significant response rate represents "a vast improvement" in the care of these pre-cancers, which are a group of diseases in which the bone marrow progenitor cells that normally morph into red and white blood cells and platelets, fail to respond to normal growth controls. That results in too many progenitor cells (also known as blasts) and too few mature blood cells, and in about 30 percent of patients, the disease progresses to acute myeloid leukemia (AML). About three-fourths of MDS patients succumb to either MDS or to AML within about 2-3 years from diagnosis.
MDS is difficult to treat, especially since it usually strikes the elderly. Ten years ago, there was little to offer patients other than blood transfusions and supportive care, Kantarjian says, and newer treatments, which include the use of stem cell transplants, are not for every patient.
Decitabine is a "biological disease modifier" that was given fast-track approval by the Food and Drug Administration in April 2003.
It is a DNA hypomethylating agent that fights cancer by reversing a chemical process (methylation) that turns off tumor-suppressor genes that protect cells from becoming cancerous. Methylation is the gradual addition of chemical units known as methyl groups to genes, and as these groups accumulate, the gene gradually shuts down. Decitabine prevents the methylation process, enabling the gene to become active again.
In addition to increased survival and time-to-progression in some patients, decitabine improved quality of life in patients who responded and eliminated the need for frequent transfusions, Kantarjian said.
Other institutions that participated in the study were The University of Rochester Medical Center, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Roswell Park Cancer Institute, Duke University Medical Center, University of Illinois, Southwest Regional Cancer Center, Rush Medical Center, and H. Lee Moffitt Cancer Center.
The study was funded by Supergen Inc., which developed decitabine.
Contact: Julie A. Penne
jpennemdanderson
University of Texas M. D. Anderson Cancer Center
пятница, 23 сентября 2011 г.
Genetics Are Key To Age At Which Girls Start Their Periods
Genetic makeup explains more than half of the variation between UK women's ages at first period, according to a study of almost 26,000 UK women published today in the May edition of Paediatric and Perinatal Epidemiology.
Age at menarche (when periods begin) is known to run in families. However, the balance of genetic and environmental influences on this has been unclear.
Scientists at The Institute of Cancer Research (ICR) analysed data from women participating in the Breakthrough Generations Study - a major UK-wide investigation into the causes of breast cancer - who had at least one other female relative also taking part.
They found that a woman's age of menarche was significantly correlated with that of her relatives. For each 12 month delay in age at menarche of an older sister, mother or paternal aunt, there was a delay of around three months on average for the younger relative; and for a maternal grandmother or maternal aunt the delay in the younger relative was about 1.5 months. Age at menarche also strongly correlated between twins, particularly identical twins.
The researchers used mathematical modelling to find that genetic factors accounted for around 57 per cent of the variation in the age of menarche of women in the study. Environmental and behavioural factors from sharing an upbringing or family life did not appear to have any detectable effect; environmental factors not shared within families accounted for the other 43 per cent in variation.
The age at which menstruation begins is important because it has been linked to risk of a number of chronic diseases including breast cancer. Risk of breast cancer gradually increases with progressively younger age at menarche and older age at menopause, possibly because women are exposed to female sex hormones for a longer period of time. Each two year delay in menarche is associated with an estimated 10 per cent reduction in the relative risk of breast cancer.
"Our study findings suggest that genetic factors have a major influence on the age women in the UK begin menstruating, and these could have an impact on breast cancer risk," lead author Danielle Morris of the ICR says. "Although some genes associated with age at menarche have been found, considerable genetic variation remains to be explained."
The Breakthrough Generations Study is a comprehensive analysis of the causes of breast cancer. A partnership between Breakthrough Breast Cancer and the ICR, it began in 2003 and will follow more than 100,000 women participants for the next 40 years to unravel the lifestyle, environmental and genetic factors that cause the disease.
This arm of the study was funded by Breakthrough Breast Cancer, the ICR and the Sir John Fisher Foundation.
The Breakthrough Generations Study is led by Professor Anthony Swerdlow, Head of the Section of Epidemiology at the ICR, and Professor Alan Ashworth, Chief Executive of the ICR and formerly head of the Breakthrough Breast Cancer Research Centre at the ICR.
Familial concordance for age at menarche: analysis from the Breakthrough Generations Study publishes today in the journal Paediatric and Perinatal Epidemiology
About breast cancer
Breast cancer is the most commonly diagnosed cancer in the UK - nearly 46,000 women and around 300 men are diagnosed every year
Breast cancer accounts for nearly one in three of all female cancers
More than 1,000 women die of breast cancer every month in the UK
The good news is that more women than ever in the UK are surviving breast cancer thanks to better awareness, better treatments and better screening
Source:
The Institute of Cancer Research (ICR)
Age at menarche (when periods begin) is known to run in families. However, the balance of genetic and environmental influences on this has been unclear.
Scientists at The Institute of Cancer Research (ICR) analysed data from women participating in the Breakthrough Generations Study - a major UK-wide investigation into the causes of breast cancer - who had at least one other female relative also taking part.
They found that a woman's age of menarche was significantly correlated with that of her relatives. For each 12 month delay in age at menarche of an older sister, mother or paternal aunt, there was a delay of around three months on average for the younger relative; and for a maternal grandmother or maternal aunt the delay in the younger relative was about 1.5 months. Age at menarche also strongly correlated between twins, particularly identical twins.
The researchers used mathematical modelling to find that genetic factors accounted for around 57 per cent of the variation in the age of menarche of women in the study. Environmental and behavioural factors from sharing an upbringing or family life did not appear to have any detectable effect; environmental factors not shared within families accounted for the other 43 per cent in variation.
The age at which menstruation begins is important because it has been linked to risk of a number of chronic diseases including breast cancer. Risk of breast cancer gradually increases with progressively younger age at menarche and older age at menopause, possibly because women are exposed to female sex hormones for a longer period of time. Each two year delay in menarche is associated with an estimated 10 per cent reduction in the relative risk of breast cancer.
"Our study findings suggest that genetic factors have a major influence on the age women in the UK begin menstruating, and these could have an impact on breast cancer risk," lead author Danielle Morris of the ICR says. "Although some genes associated with age at menarche have been found, considerable genetic variation remains to be explained."
The Breakthrough Generations Study is a comprehensive analysis of the causes of breast cancer. A partnership between Breakthrough Breast Cancer and the ICR, it began in 2003 and will follow more than 100,000 women participants for the next 40 years to unravel the lifestyle, environmental and genetic factors that cause the disease.
This arm of the study was funded by Breakthrough Breast Cancer, the ICR and the Sir John Fisher Foundation.
The Breakthrough Generations Study is led by Professor Anthony Swerdlow, Head of the Section of Epidemiology at the ICR, and Professor Alan Ashworth, Chief Executive of the ICR and formerly head of the Breakthrough Breast Cancer Research Centre at the ICR.
Familial concordance for age at menarche: analysis from the Breakthrough Generations Study publishes today in the journal Paediatric and Perinatal Epidemiology
About breast cancer
Breast cancer is the most commonly diagnosed cancer in the UK - nearly 46,000 women and around 300 men are diagnosed every year
Breast cancer accounts for nearly one in three of all female cancers
More than 1,000 women die of breast cancer every month in the UK
The good news is that more women than ever in the UK are surviving breast cancer thanks to better awareness, better treatments and better screening
Source:
The Institute of Cancer Research (ICR)
вторник, 20 сентября 2011 г.
Parkinson's Disease: Blood-Related Genetic Mechanisms Important
What does the genetics of blood cells have to do with brain cells related to Parkinson's disease? From an unusual collaboration of neurologists and a pharmacologist comes the surprising answer: Genetic mechanisms at play in blood cells also control a gene and protein that cause Parkinson's disease.
The finding, by scientists from the University of Wisconsin School of Medicine and Public Health (SMPH), Harvard University-affiliated Brigham and Women's Hospital and the University of Ottawa, may lead to new treatments for the neurological disorder that affects as many as 1.5 million Americans.
The study is published in the Proceedings of the National Academy of Sciences Online Early Edition the week of July 21-25, 2008.
Patients with Parkinson's disease (PD) have elevated levels of the protein called alpha-synuclein in their brains. As the protein clumps, or aggregates, the resulting toxicity causes the death of neurons that produce the brain chemical dopamine. Consequently, nerves and muscles that control movement and coordination are destroyed.
The researchers discovered that the activity of three genes that control the synthesis of heme, the major component of hemoglobin that allows red blood cells to carry oxygen, precisely matched the activity of the alpha-synuclein gene, suggesting a common switch controlling both.
The scientists then found that a protein called GATA-1, which turns on the blood-related genes, was also a major switch for alpha-synuclein expression, and that it induced a significant increase in alpha-synuclein protein. Finally, they demonstrated that a related protein - GATA-2 - was expressed in PD-vulnerable brain cells and directly controlled alpha-synuclein production.
"Very little was known previously about what turns on alpha-synuclein in brain cells and causes variations in its expression," says Emery Bresnick, a UW-Madison professor of pharmacology who is an expert on GATA factors and their functions in blood. "Understanding how GATA factors work in the brain may provide fundamental insights into the biology of Parkinson's disease."
The new knowledge also may allow scientists to design therapies that keep alpha-synuclein levels within the normal range.
"Simply lowering alpha-synuclein levels by 40 percent may be enough to treat some forms of Parkinson's disease," says Dr. Clemens Scherzer of Harvard. "So far, researchers have focused on ways to get rid of too much 'bad' alpha-synuclein in Parkinson patients' brains. Now we will be able to tackle the problem from the production site, and search for new therapies that lower alpha-synuclein production up front."
Scherzer and Dr. Michael Schlossmacher, now at Ottawa, had independently analyzed the blood of PD patients and controls in a search for genes that were active in the disease. They both were surprised to notice large amounts of alpha-synuclein in the blood. To understand what it was doing there, Scherzer's group used gene chip data to see whether any of the thousands of genes active in blood were linked to alpha-synuclein. They found a gene expression pattern composed of alpha-synuclein and the heme genes, one of which Bresnick had previously shown to be a direct GATA-1 target gene.
The neurologists contacted Bresnick. The UW group rapidly determined that GATA-1 directly activated the alpha-synuclein gene, and that finding led the collaborators to discover that GATA-2 is expressed in regions of the brain that are relevant to PD.
"We all were excited because we realized that GATA-2 was active in the relevant brain regions, and so there could be a connection," says Bresnick. Together the researchers set out to examine whether common mechanisms activated alpha-synuclein transcription in both the blood and nerve cells.
The studies showed that GATA-1 and GATA-2 proteins find the alpha-synuclein gene, stick to it and then directly control it.
"This is not an indirect pathway; it is direct regulation of the gene," says Bresnick. "This directness provides the simplest scenario for creating a therapeutic strategy."
Bresnick, Schlossmacher and Scherzer are working with geneticists to see if possible abnormalities in the GATA-2 gene may exist in PD patients, stimulating more production of alpha-syinuclein.
"The discovery of the link between GATA proteins and the alpha-synuclein gene is like finding a long-sought-after molecular switch," says Schlossmacher. "We were very fortunate to find in Emery Bresnick's team the ideal partner in this endeavor."
The family of GATA factors consists of six members, and some of them, beyond GATA-2, may also be influencing alpha-synuclein expression in the brain, adds Schlossmacher.
"Identifying these would further add to the complexity of regulating the production of the 'bad player' in Parkinson's disease," he says.
Says Bresnick, "The $10 million question will be: Does deregulation of the GATA mechanism in humans lead to alpha-synuclein overproduction and Parkinson's disease?"
Source: Dian Land
University of Wisconsin-Madison
The finding, by scientists from the University of Wisconsin School of Medicine and Public Health (SMPH), Harvard University-affiliated Brigham and Women's Hospital and the University of Ottawa, may lead to new treatments for the neurological disorder that affects as many as 1.5 million Americans.
The study is published in the Proceedings of the National Academy of Sciences Online Early Edition the week of July 21-25, 2008.
Patients with Parkinson's disease (PD) have elevated levels of the protein called alpha-synuclein in their brains. As the protein clumps, or aggregates, the resulting toxicity causes the death of neurons that produce the brain chemical dopamine. Consequently, nerves and muscles that control movement and coordination are destroyed.
The researchers discovered that the activity of three genes that control the synthesis of heme, the major component of hemoglobin that allows red blood cells to carry oxygen, precisely matched the activity of the alpha-synuclein gene, suggesting a common switch controlling both.
The scientists then found that a protein called GATA-1, which turns on the blood-related genes, was also a major switch for alpha-synuclein expression, and that it induced a significant increase in alpha-synuclein protein. Finally, they demonstrated that a related protein - GATA-2 - was expressed in PD-vulnerable brain cells and directly controlled alpha-synuclein production.
"Very little was known previously about what turns on alpha-synuclein in brain cells and causes variations in its expression," says Emery Bresnick, a UW-Madison professor of pharmacology who is an expert on GATA factors and their functions in blood. "Understanding how GATA factors work in the brain may provide fundamental insights into the biology of Parkinson's disease."
The new knowledge also may allow scientists to design therapies that keep alpha-synuclein levels within the normal range.
"Simply lowering alpha-synuclein levels by 40 percent may be enough to treat some forms of Parkinson's disease," says Dr. Clemens Scherzer of Harvard. "So far, researchers have focused on ways to get rid of too much 'bad' alpha-synuclein in Parkinson patients' brains. Now we will be able to tackle the problem from the production site, and search for new therapies that lower alpha-synuclein production up front."
Scherzer and Dr. Michael Schlossmacher, now at Ottawa, had independently analyzed the blood of PD patients and controls in a search for genes that were active in the disease. They both were surprised to notice large amounts of alpha-synuclein in the blood. To understand what it was doing there, Scherzer's group used gene chip data to see whether any of the thousands of genes active in blood were linked to alpha-synuclein. They found a gene expression pattern composed of alpha-synuclein and the heme genes, one of which Bresnick had previously shown to be a direct GATA-1 target gene.
The neurologists contacted Bresnick. The UW group rapidly determined that GATA-1 directly activated the alpha-synuclein gene, and that finding led the collaborators to discover that GATA-2 is expressed in regions of the brain that are relevant to PD.
"We all were excited because we realized that GATA-2 was active in the relevant brain regions, and so there could be a connection," says Bresnick. Together the researchers set out to examine whether common mechanisms activated alpha-synuclein transcription in both the blood and nerve cells.
The studies showed that GATA-1 and GATA-2 proteins find the alpha-synuclein gene, stick to it and then directly control it.
"This is not an indirect pathway; it is direct regulation of the gene," says Bresnick. "This directness provides the simplest scenario for creating a therapeutic strategy."
Bresnick, Schlossmacher and Scherzer are working with geneticists to see if possible abnormalities in the GATA-2 gene may exist in PD patients, stimulating more production of alpha-syinuclein.
"The discovery of the link between GATA proteins and the alpha-synuclein gene is like finding a long-sought-after molecular switch," says Schlossmacher. "We were very fortunate to find in Emery Bresnick's team the ideal partner in this endeavor."
The family of GATA factors consists of six members, and some of them, beyond GATA-2, may also be influencing alpha-synuclein expression in the brain, adds Schlossmacher.
"Identifying these would further add to the complexity of regulating the production of the 'bad player' in Parkinson's disease," he says.
Says Bresnick, "The $10 million question will be: Does deregulation of the GATA mechanism in humans lead to alpha-synuclein overproduction and Parkinson's disease?"
Source: Dian Land
University of Wisconsin-Madison
суббота, 17 сентября 2011 г.
Particle Trap Paves Way For Personalized Medicine
Sequencing DNA base pairs - the individual molecules that make up DNA - is key for medical researchers working toward personalized medicine. Being able to isolate, study and sequence these DNA molecules would allow scientists to tailor diagnostic testing, therapies and treatments based on each patient's individual genetic makeup.
But being able to isolate individual molecules like DNA base pairs, which are just two nanometers across - or about 1/50,000th the diameter of a human hair - is incredibly expensive and difficult to control. In addition, devising a way to trap DNA molecules in their natural aqueous environment further complicates things. Scientists have spent the past decade struggling to isolate and trap individual DNA molecules in an aqueous solution by trying to thread it through a tiny hole the size of DNA, called a "nanopore," which is exceedingly difficult to make and control.
Now a team led by Yale University researchers has proven that isolating individual charged particles, like DNA molecules, is indeed possible using a method called "Paul trapping," which uses oscillating electric fields to confine the particles to a space only nanometers in size. (The technique is named for Wolfgang Paul, who won the Nobel Prize for the discovery.) Until now, scientists have only been able to use Paul traps for particles in a vacuum, but the Yale team was able to confine a charged test particle - in this case, a polystyrene bead - to an accuracy of just 10 nanometers in aqueous solutions between quadruple microelectrodes that supplied the electric field.
Their device can be contained on a single chip and is simple and inexpensive to manufacture. "The idea would be that doctors could take a tiny drop of blood from patients and be able to run diagnostic tests on it right there in their office, instead of sending it away to a lab where testing can take days and is expensive," said Weihua Guan, a Yale engineering graduate student who led the project.
In addition to diagnostics, this "lab-on-a-chip" would have a wide range of applications, Guan said, such as being able to analyze how individual cells respond to different stimulation. While there are several other techniques for cell-manipulation available now, such as optical tweezers, the Yale team's approach actually works better as the size of the targets gets smaller, contrary to other approaches.
The team, whose findings appear in the May 23 Early Edition of the Proceedings of the National Academy of Sciences, used charged polystyrene beads rather than actual DNA molecules, along with a two-dimensional trap to prove that the technique worked. Next, they will work toward creating a 3-D trap using DNA molecules, which, at two nanometers, are even smaller than the test beads. They hope to have a working, 3-D trap using DNA molecules in the next year or two. The project is funded by a National Institutes of Health program that aims to sequence a patient's entire genome for less than $1,000.
"This is the future of personalized medicine," Guan said.
Notes:
The project was directed by Mark Reed (Yale University) and Predrag Krstic (Oak Ridge National Laboratory). Other authors of the paper include Sony Joseph and Jae Hyun Park (Oak Ridge National Laboratory).
DOI: 10.1073/pnas.1100977108
Source:
Suzanne Taylor Muzzin
Yale University
But being able to isolate individual molecules like DNA base pairs, which are just two nanometers across - or about 1/50,000th the diameter of a human hair - is incredibly expensive and difficult to control. In addition, devising a way to trap DNA molecules in their natural aqueous environment further complicates things. Scientists have spent the past decade struggling to isolate and trap individual DNA molecules in an aqueous solution by trying to thread it through a tiny hole the size of DNA, called a "nanopore," which is exceedingly difficult to make and control.
Now a team led by Yale University researchers has proven that isolating individual charged particles, like DNA molecules, is indeed possible using a method called "Paul trapping," which uses oscillating electric fields to confine the particles to a space only nanometers in size. (The technique is named for Wolfgang Paul, who won the Nobel Prize for the discovery.) Until now, scientists have only been able to use Paul traps for particles in a vacuum, but the Yale team was able to confine a charged test particle - in this case, a polystyrene bead - to an accuracy of just 10 nanometers in aqueous solutions between quadruple microelectrodes that supplied the electric field.
Their device can be contained on a single chip and is simple and inexpensive to manufacture. "The idea would be that doctors could take a tiny drop of blood from patients and be able to run diagnostic tests on it right there in their office, instead of sending it away to a lab where testing can take days and is expensive," said Weihua Guan, a Yale engineering graduate student who led the project.
In addition to diagnostics, this "lab-on-a-chip" would have a wide range of applications, Guan said, such as being able to analyze how individual cells respond to different stimulation. While there are several other techniques for cell-manipulation available now, such as optical tweezers, the Yale team's approach actually works better as the size of the targets gets smaller, contrary to other approaches.
The team, whose findings appear in the May 23 Early Edition of the Proceedings of the National Academy of Sciences, used charged polystyrene beads rather than actual DNA molecules, along with a two-dimensional trap to prove that the technique worked. Next, they will work toward creating a 3-D trap using DNA molecules, which, at two nanometers, are even smaller than the test beads. They hope to have a working, 3-D trap using DNA molecules in the next year or two. The project is funded by a National Institutes of Health program that aims to sequence a patient's entire genome for less than $1,000.
"This is the future of personalized medicine," Guan said.
Notes:
The project was directed by Mark Reed (Yale University) and Predrag Krstic (Oak Ridge National Laboratory). Other authors of the paper include Sony Joseph and Jae Hyun Park (Oak Ridge National Laboratory).
DOI: 10.1073/pnas.1100977108
Source:
Suzanne Taylor Muzzin
Yale University
среда, 14 сентября 2011 г.
NIST, Army Researchers Pave The Way For Anthrax Spore Standards
Researchers from the National Institute of Standards and Technology (NIST) and the U.S. Army Dugway (Utah) Proving Ground have developed reliable methods based on DNA analysis to assess the concentration and viability of anthrax spores after prolonged storage. The techniques and data are essential steps in developing a reliable reference standard for anthrax detection and decontamination.
Bacillus anthracis, the bacterium that causes anthrax, has been a centuries-old threat to human health. In 2001, it was used as a letter-borne terrorist weapon that killed five Americans. Since the tenacious bacterium can survive for decades in a stable spore state, the Department of Homeland Security (DHS) has been working with NIST to develop anthrax spore reference materials. These materials could be used as controls in laboratory studies of anthrax, to calibrate spore detection equipment and to assess the efficiency of spore decontamination methods.
Because sample stability is a key requirement for reference materials, NIST and Army researchers recently compared different methods for measuring the concentration, biological activity and stability of laboratory-grade Bacillus anthracis spores under different storage conditions. Bacillus anthracis (Sterne), a harmless vaccine strain, was used in the study. The results of the research will be published in an upcoming issue of the Journal of Applied Microbiology.*
Working with samples that had been stored up to 2 1/2 years, the research team used two classic microbiological techniques to quantify the Bacillus anthracis concentrations: counting spores under a microscope and counting the bacterial colonies that grow after the spores are spread on a nutrient surface and germinate. The latter yields valuable data on the biological activity of the samples; however, only viable cells are counted and counts may be underestimated if cell clumping occurs. A better approach is to measure the amount of genetic material present in the sample. This method not only measures the DNA extracted from viable anthrax spores but also DNA in solution from damaged spores, cell debris and spore fragments - giving a truer measure of the source of DNA in the samples. Additionally, many of the new instruments available for rapid detection of anthrax spores are based on DNA markers, so it is important to accurately measure the DNA content of the reference samples that will be used to test and calibrate these devices.
Traditional methods for extracting DNA from Bacillus anthracis spores are too harsh to produce material suitable for reliable measurements. To overcome this obstacle, the team developed an extraction technique that used chemicals and enzymes to disrupt intact spores into releasing their DNA in a relatively pure state.
The NIST-Army study showed that laboratory-grade Bacillus anthracis spores in suspension maintained their viability and did not clump when stored for up to 900 days. The classical method for counting spores yielded comparable results to the DNA measurements used to determine spore concentrations. The results demonstrate that research quality spores can be stored for long periods of time and still maintain their important properties, proving that uniform and consistent reference materials are possible.
* J.L. Almeida, B. Harper and K.D. Cole. Bacillus anthracis spore suspensions: determination of stability and comparison of enumeration techniques. Journal of Applied Microbiology, 2008.
Source: Michael E. Newman
National Institute of Standards and Technology (NIST)
Bacillus anthracis, the bacterium that causes anthrax, has been a centuries-old threat to human health. In 2001, it was used as a letter-borne terrorist weapon that killed five Americans. Since the tenacious bacterium can survive for decades in a stable spore state, the Department of Homeland Security (DHS) has been working with NIST to develop anthrax spore reference materials. These materials could be used as controls in laboratory studies of anthrax, to calibrate spore detection equipment and to assess the efficiency of spore decontamination methods.
Because sample stability is a key requirement for reference materials, NIST and Army researchers recently compared different methods for measuring the concentration, biological activity and stability of laboratory-grade Bacillus anthracis spores under different storage conditions. Bacillus anthracis (Sterne), a harmless vaccine strain, was used in the study. The results of the research will be published in an upcoming issue of the Journal of Applied Microbiology.*
Working with samples that had been stored up to 2 1/2 years, the research team used two classic microbiological techniques to quantify the Bacillus anthracis concentrations: counting spores under a microscope and counting the bacterial colonies that grow after the spores are spread on a nutrient surface and germinate. The latter yields valuable data on the biological activity of the samples; however, only viable cells are counted and counts may be underestimated if cell clumping occurs. A better approach is to measure the amount of genetic material present in the sample. This method not only measures the DNA extracted from viable anthrax spores but also DNA in solution from damaged spores, cell debris and spore fragments - giving a truer measure of the source of DNA in the samples. Additionally, many of the new instruments available for rapid detection of anthrax spores are based on DNA markers, so it is important to accurately measure the DNA content of the reference samples that will be used to test and calibrate these devices.
Traditional methods for extracting DNA from Bacillus anthracis spores are too harsh to produce material suitable for reliable measurements. To overcome this obstacle, the team developed an extraction technique that used chemicals and enzymes to disrupt intact spores into releasing their DNA in a relatively pure state.
The NIST-Army study showed that laboratory-grade Bacillus anthracis spores in suspension maintained their viability and did not clump when stored for up to 900 days. The classical method for counting spores yielded comparable results to the DNA measurements used to determine spore concentrations. The results demonstrate that research quality spores can be stored for long periods of time and still maintain their important properties, proving that uniform and consistent reference materials are possible.
* J.L. Almeida, B. Harper and K.D. Cole. Bacillus anthracis spore suspensions: determination of stability and comparison of enumeration techniques. Journal of Applied Microbiology, 2008.
Source: Michael E. Newman
National Institute of Standards and Technology (NIST)
воскресенье, 11 сентября 2011 г.
Biologists Pinpoint A Genetic Change That Helps Tumors Move To Other Parts Of The Body
MIT cancer biologists have identified a genetic change that makes lung tumors more likely to spread to other parts of the body. The findings, to be published in the April 6 online issue of Nature, offers new insight into how lung cancers metastasize and could help identify drug targets to combat metastatic tumors, which account for 90 percent of cancer deaths.
The researchers, led by Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT, found the alteration while studying a mouse model of lung cancer. They then compared their mouse data to genetic profiles of human lung tumors and found that reduced activity of the same gene, NKX2-1, is associated with higher death rates for lung-cancer patients.
This study represents an important step in understanding how changes that disable this gene would make tumors more aggressive, says Monte Winslow, a senior postdoctoral associate in Jacks' lab and lead author of a paper.
Understanding the role of NKX2-1 may help scientists pursue drugs that could counteract its loss. Right now, "the sad reality is that if you could tell a patient whether their cancer has turned down this gene, you would know they will have a worse outcome, but it wouldn't change the treatment," Winslow says.
Winslow and his colleagues at the Koch Institute studied mice that are genetically programmed to develop lung tumors. The mice's lung cells can be induced to express an activated form of the cancer-causing gene Kras, and the tumor suppressor gene p53 is deleted. While all of those mice develop lung tumors, only a subset of those tumors metastasizes, suggesting that additional changes are required for the cancer to spread.
The researchers analyzed the genomes of metastatic and non-metastatic tumors in hopes of finding some genetic differences that would account for the discrepancy. The absence of NKX2-1 activity in metastatic tumors was the most striking difference, Winslow says.
The NKX2-1 gene codes for a transcription factor a protein that controls expression of other genes. Its normal function is to control development of the lung, as well as the thyroid and some parts of the brain. When cancerous cells turn down the expression of the gene, they appear to revert to an immature state and gain the ability to detach from the lungs and spread through the body, seeding new tumors.
Once the researchers identified NKX2-1 as a gene important to metastasis, they started to look into the effects of the genes that it regulates. They zeroed in on a gene called HMGA2, which had been previously implicated in other types of cancer. It appears that NKX2-1 represses HMGA2 in adult tissues. When NKX2-1 is shut off in cancer cells, HMGA2 turns back on and helps the tumor to become more aggressive.
They also found that human tumors with NKX2-1 missing and HMGA turned on tended to be metastatic, though not all metastatic tumors fit that profile.
It would be difficult to target NKX2-1 with a drug because it's much harder to develop drugs that turn a gene back on than shut it off, Winslow noted. A more promising possibility is targeting HMGA2 or other genes that NKX2-1 represses.
Jacks' lab is now looking at other types of cancer, to see if NKX2-1 or HMGA2 have the same role in other metastatic cancers. "It's great to find something that's important in lung cancer metastasis, but it would be even better if it controlled metastasis in even a subset of other cancer types," Winslow says.
Source: Massachusetts Institute of Technology (MIT)
The researchers, led by Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT, found the alteration while studying a mouse model of lung cancer. They then compared their mouse data to genetic profiles of human lung tumors and found that reduced activity of the same gene, NKX2-1, is associated with higher death rates for lung-cancer patients.
This study represents an important step in understanding how changes that disable this gene would make tumors more aggressive, says Monte Winslow, a senior postdoctoral associate in Jacks' lab and lead author of a paper.
Understanding the role of NKX2-1 may help scientists pursue drugs that could counteract its loss. Right now, "the sad reality is that if you could tell a patient whether their cancer has turned down this gene, you would know they will have a worse outcome, but it wouldn't change the treatment," Winslow says.
Winslow and his colleagues at the Koch Institute studied mice that are genetically programmed to develop lung tumors. The mice's lung cells can be induced to express an activated form of the cancer-causing gene Kras, and the tumor suppressor gene p53 is deleted. While all of those mice develop lung tumors, only a subset of those tumors metastasizes, suggesting that additional changes are required for the cancer to spread.
The researchers analyzed the genomes of metastatic and non-metastatic tumors in hopes of finding some genetic differences that would account for the discrepancy. The absence of NKX2-1 activity in metastatic tumors was the most striking difference, Winslow says.
The NKX2-1 gene codes for a transcription factor a protein that controls expression of other genes. Its normal function is to control development of the lung, as well as the thyroid and some parts of the brain. When cancerous cells turn down the expression of the gene, they appear to revert to an immature state and gain the ability to detach from the lungs and spread through the body, seeding new tumors.
Once the researchers identified NKX2-1 as a gene important to metastasis, they started to look into the effects of the genes that it regulates. They zeroed in on a gene called HMGA2, which had been previously implicated in other types of cancer. It appears that NKX2-1 represses HMGA2 in adult tissues. When NKX2-1 is shut off in cancer cells, HMGA2 turns back on and helps the tumor to become more aggressive.
They also found that human tumors with NKX2-1 missing and HMGA turned on tended to be metastatic, though not all metastatic tumors fit that profile.
It would be difficult to target NKX2-1 with a drug because it's much harder to develop drugs that turn a gene back on than shut it off, Winslow noted. A more promising possibility is targeting HMGA2 or other genes that NKX2-1 represses.
Jacks' lab is now looking at other types of cancer, to see if NKX2-1 or HMGA2 have the same role in other metastatic cancers. "It's great to find something that's important in lung cancer metastasis, but it would be even better if it controlled metastasis in even a subset of other cancer types," Winslow says.
Source: Massachusetts Institute of Technology (MIT)
четверг, 8 сентября 2011 г.
Gender And Genes Impact On Fat Storage - Belly Or Hip
The age-old question of why men store fat in their bellies and women store it in their hips may have finally been answered: Genetically speaking, the fat tissue is almost completely different.
"We found that out of about 40,000 mouse genes, only 138 are commonly found in both male and female fat cells," said Dr. Deborah Clegg, assistant professor of internal medicine at UT Southwestern Medical Center and senior author of the study appearing in the International Journal of Obesity. "This was completely unexpected. We expected the exact opposite - that 138 would be different and the rest would be the same between the sexes."
The study involved mice, which distribute their fat in a sexually dimorphic pattern similar to humans.
"Given the difference in gene expression profiles, a female fat tissue won't behave anything like a male fat tissue and vice versa," Dr. Clegg said. "The notion that fat cells between males and females are alike is inconsistent with our findings."
In humans, men are more likely to carry extra weight around their guts while pre-menopausal women store it in their butts, thighs and hips. The bad news for men is that belly, or visceral, fat has been associated with numerous obesity-related diseases including diabetes and heart disease. Women, on the other hand, are generally protected from these obesity-related disorders until menopause, when their ovarian hormone levels drop and fat storage tends to shift from their rear ends to their waists.
"Although our new findings don't explain why women begin storing fat in their bellies after menopause, the results do bring us a step closer to understanding the mechanisms behind the unwanted shift," Dr. Clegg said.
For this study, researchers used a microarray analysis to determine whether male fat cells and female fat cells were different between the waist and hips and if they were different based on gender at a genetic level.
Because the fat distribution patterns of male and female mice are similar to those of humans, the researchers used the animals to compare genes from the belly and hip fat pads of male mice, female mice and female mice whose ovaries had been removed - a condition that closely mimics human menopause. Waist and hip fat (subcutaneous fat) generally accumulates outside the muscle wall, whereas belly fat (visceral fat), a major health concern in men and postmenopausal women, develops around the internal organs.
In addition to the genetic differences among fat tissues, the researchers found that male mice that consumed a high-fat diet for 12 weeks gained more weight than female mice on the same diet. The males' fat tissue, particularly their belly fat, became highly inflamed, while the females had lower levels of genes associated with inflammation. The female mice whose ovaries had been removed, however, gained weight on the high-fat diet more like the males and deposited this fat in their bellies, also like the males.
"The fat of the female mice whose ovaries had been removed was inflamed and was starting to look like the unhealthy male fat," Dr. Clegg said. "However, estrogen replacement therapy in the mice reduced the inflammation and returned their fat distribution to that of mice with their ovaries intact."
Dr. Clegg said the results suggest that hormones made by the ovaries may be critical in determining where fat is deposited. Her overall goal is to determine how fat tissue is affected by sex hormones and whether it would be possible to develop a "designer" hormone replacement therapy that protected postmenopausal women from belly fat and related diseases such as metabolic syndrome.
Researchers from Oregon Health and Science University, Boston University School of Medicine and the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University also contributed to the study. The study was supported by the Society for Women's Health Research.
Source:
Kristen Holland Shear
UT Southwestern Medical Center
"We found that out of about 40,000 mouse genes, only 138 are commonly found in both male and female fat cells," said Dr. Deborah Clegg, assistant professor of internal medicine at UT Southwestern Medical Center and senior author of the study appearing in the International Journal of Obesity. "This was completely unexpected. We expected the exact opposite - that 138 would be different and the rest would be the same between the sexes."
The study involved mice, which distribute their fat in a sexually dimorphic pattern similar to humans.
"Given the difference in gene expression profiles, a female fat tissue won't behave anything like a male fat tissue and vice versa," Dr. Clegg said. "The notion that fat cells between males and females are alike is inconsistent with our findings."
In humans, men are more likely to carry extra weight around their guts while pre-menopausal women store it in their butts, thighs and hips. The bad news for men is that belly, or visceral, fat has been associated with numerous obesity-related diseases including diabetes and heart disease. Women, on the other hand, are generally protected from these obesity-related disorders until menopause, when their ovarian hormone levels drop and fat storage tends to shift from their rear ends to their waists.
"Although our new findings don't explain why women begin storing fat in their bellies after menopause, the results do bring us a step closer to understanding the mechanisms behind the unwanted shift," Dr. Clegg said.
For this study, researchers used a microarray analysis to determine whether male fat cells and female fat cells were different between the waist and hips and if they were different based on gender at a genetic level.
Because the fat distribution patterns of male and female mice are similar to those of humans, the researchers used the animals to compare genes from the belly and hip fat pads of male mice, female mice and female mice whose ovaries had been removed - a condition that closely mimics human menopause. Waist and hip fat (subcutaneous fat) generally accumulates outside the muscle wall, whereas belly fat (visceral fat), a major health concern in men and postmenopausal women, develops around the internal organs.
In addition to the genetic differences among fat tissues, the researchers found that male mice that consumed a high-fat diet for 12 weeks gained more weight than female mice on the same diet. The males' fat tissue, particularly their belly fat, became highly inflamed, while the females had lower levels of genes associated with inflammation. The female mice whose ovaries had been removed, however, gained weight on the high-fat diet more like the males and deposited this fat in their bellies, also like the males.
"The fat of the female mice whose ovaries had been removed was inflamed and was starting to look like the unhealthy male fat," Dr. Clegg said. "However, estrogen replacement therapy in the mice reduced the inflammation and returned their fat distribution to that of mice with their ovaries intact."
Dr. Clegg said the results suggest that hormones made by the ovaries may be critical in determining where fat is deposited. Her overall goal is to determine how fat tissue is affected by sex hormones and whether it would be possible to develop a "designer" hormone replacement therapy that protected postmenopausal women from belly fat and related diseases such as metabolic syndrome.
Researchers from Oregon Health and Science University, Boston University School of Medicine and the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University also contributed to the study. The study was supported by the Society for Women's Health Research.
Source:
Kristen Holland Shear
UT Southwestern Medical Center
понедельник, 5 сентября 2011 г.
NYIT Professor Discovers Next Generation Of DNA And RNA Microarrays
A novel invention developed
by a scientist from New York Institute of Technology (NYIT) could
revolutionize biological and clinical research and may lead to treatments
for cancer, AIDS, Alzheimer's, diabetes, and genetic and infectious
diseases.
Since the discovery of DNA, biologists have worked to unlock the
secrets of the human cell. Scientist Claude E. Gagna, Ph.D., an associate
professor at NYIT's School of Health Professions, Behavioral and Life
Sciences, discovered how to immobilize intact double-stranded (ds-),
multi-stranded or alternative DNA and RNA on one microarray. This
immobilization allows scientists to duplicate the environment of a cell,
and study, examine and experiment with human, bacterial and viral genes.
This invention provides the methodology to analyze more than 150,000
non-denatured genes.
"This patent represents a leap forward from conventional DNA
microarrays that use hybridization," says Gagna, a molecular
biologist-pathologist who performs research in the structure-function of
DNA in normal and diseased cells. "This will help pharmaceutical companies
produce new classes of drugs that target genes, with fewer side effects,"
he adds. "It will lower the cost and increase the speed of drug discovery,
saving millions of dollars."
The "Gagna/NYIT Multi-Stranded and Alternative DNA, RNA and Plasmid
Microarray," has been patented (#6,936,461) in the United States and is
pending in Europe and Asia. Gagna's discovery will help scientists
understand how transitions in DNA structure regulate gene expression (B-DNA
to Z-DNA), and how DNA-protein, and DNA-drug interactions regulate genes.
The breakthrough can aid in genetic screening, clinical diagnosis,
forensics, DNA synthesis-sequencing and biodefense.
In the near future, practical applications of the patent will include
enabling researchers to directly target and inhibit mutated genes and/or
proteins that are responsible for pathologies, making it easier to treat or
even cure disease. A discussion of the patent and two new applications --
known as transitional structural chemogenomics and transitional structural
chemoproteomics -- was published in the May 2006 issue of Medical
Hypotheses (67:1099-1114).
Additionally, Gagna has developed a novel surface that increases the
adherence of the DNA to the microarray so that any type of nucleic acid can
be anchored. Unlike conventional microarrays, which immobilize
single-stranded DNA, scientists will now be able to "secure intact,
non-denatured, unaltered ds-DNA, triplex-, quadruplex-, or pentaplex DNA
onto the microarray," says Gagna. "With this technology, one day we will
have tailor-made molecular medicine for patients."
Invented in 1991, DNA microarrays have become one of the most powerful
research tools. Scientists are able to perform thousands of experiments
with incredible accuracy and speed. According to MarketResearch, by
2009, sales of DNA microarrays are projected to be more than $5.3 billion a
year.
Gagna, a resident of Palisades Park, N.J., performs research in his lab
at New York College of Osteopathic Medicine of NYIT. He is an adjunct
assistant professor at the New Jersey Medical School: Department's of
Pathology and Medicine. Gagna earned a Doctor of Philosophy in anatomy and
biochemistry from New York University (NYU), Basic Medical Sciences. He
completed his postdoctoral work at NYU and at New Jersey Medical School,
researching DNA. Gagna received a Master of Science in anatomy from
Fairleigh Dickinson University, and a Bachelor of Science in biology from
St. Peters College.
For more information about Gagna's patent, please visit
nyit.edu/dnamicroarrays.
About NYIT
NYIT is the college of choice for more than 14,000 students enrolled in
more than 100 specialized courses of study leading to undergraduate,
graduate and professional degrees in academic areas such as architecture
and design; arts and sciences; education and professional services;
engineering and technology; extended education; health professions,
behavioral and life sciences; management; and osteopathic medicine. As a
private, nonprofit, independent institution of higher learning, NYIT
embraces an educational philosophy of career-oriented professional
education for all qualified students and supports applications-oriented
research to benefit the greater global community. Students attend classes
at NYIT's campuses in Manhattan and Long Island, as well as online and in a
number of programs throughout the world. To date, more than 69,000 alumni
have earned degrees at NYIT. For more information, visit
nyit.edu.
New York Institute of Technology
nyit.edu
by a scientist from New York Institute of Technology (NYIT) could
revolutionize biological and clinical research and may lead to treatments
for cancer, AIDS, Alzheimer's, diabetes, and genetic and infectious
diseases.
Since the discovery of DNA, biologists have worked to unlock the
secrets of the human cell. Scientist Claude E. Gagna, Ph.D., an associate
professor at NYIT's School of Health Professions, Behavioral and Life
Sciences, discovered how to immobilize intact double-stranded (ds-),
multi-stranded or alternative DNA and RNA on one microarray. This
immobilization allows scientists to duplicate the environment of a cell,
and study, examine and experiment with human, bacterial and viral genes.
This invention provides the methodology to analyze more than 150,000
non-denatured genes.
"This patent represents a leap forward from conventional DNA
microarrays that use hybridization," says Gagna, a molecular
biologist-pathologist who performs research in the structure-function of
DNA in normal and diseased cells. "This will help pharmaceutical companies
produce new classes of drugs that target genes, with fewer side effects,"
he adds. "It will lower the cost and increase the speed of drug discovery,
saving millions of dollars."
The "Gagna/NYIT Multi-Stranded and Alternative DNA, RNA and Plasmid
Microarray," has been patented (#6,936,461) in the United States and is
pending in Europe and Asia. Gagna's discovery will help scientists
understand how transitions in DNA structure regulate gene expression (B-DNA
to Z-DNA), and how DNA-protein, and DNA-drug interactions regulate genes.
The breakthrough can aid in genetic screening, clinical diagnosis,
forensics, DNA synthesis-sequencing and biodefense.
In the near future, practical applications of the patent will include
enabling researchers to directly target and inhibit mutated genes and/or
proteins that are responsible for pathologies, making it easier to treat or
even cure disease. A discussion of the patent and two new applications --
known as transitional structural chemogenomics and transitional structural
chemoproteomics -- was published in the May 2006 issue of Medical
Hypotheses (67:1099-1114).
Additionally, Gagna has developed a novel surface that increases the
adherence of the DNA to the microarray so that any type of nucleic acid can
be anchored. Unlike conventional microarrays, which immobilize
single-stranded DNA, scientists will now be able to "secure intact,
non-denatured, unaltered ds-DNA, triplex-, quadruplex-, or pentaplex DNA
onto the microarray," says Gagna. "With this technology, one day we will
have tailor-made molecular medicine for patients."
Invented in 1991, DNA microarrays have become one of the most powerful
research tools. Scientists are able to perform thousands of experiments
with incredible accuracy and speed. According to MarketResearch, by
2009, sales of DNA microarrays are projected to be more than $5.3 billion a
year.
Gagna, a resident of Palisades Park, N.J., performs research in his lab
at New York College of Osteopathic Medicine of NYIT. He is an adjunct
assistant professor at the New Jersey Medical School: Department's of
Pathology and Medicine. Gagna earned a Doctor of Philosophy in anatomy and
biochemistry from New York University (NYU), Basic Medical Sciences. He
completed his postdoctoral work at NYU and at New Jersey Medical School,
researching DNA. Gagna received a Master of Science in anatomy from
Fairleigh Dickinson University, and a Bachelor of Science in biology from
St. Peters College.
For more information about Gagna's patent, please visit
nyit.edu/dnamicroarrays.
About NYIT
NYIT is the college of choice for more than 14,000 students enrolled in
more than 100 specialized courses of study leading to undergraduate,
graduate and professional degrees in academic areas such as architecture
and design; arts and sciences; education and professional services;
engineering and technology; extended education; health professions,
behavioral and life sciences; management; and osteopathic medicine. As a
private, nonprofit, independent institution of higher learning, NYIT
embraces an educational philosophy of career-oriented professional
education for all qualified students and supports applications-oriented
research to benefit the greater global community. Students attend classes
at NYIT's campuses in Manhattan and Long Island, as well as online and in a
number of programs throughout the world. To date, more than 69,000 alumni
have earned degrees at NYIT. For more information, visit
nyit.edu.
New York Institute of Technology
nyit.edu
пятница, 2 сентября 2011 г.
Revealing The Unique Survival Mechanisms Of A Single-Cell Marine Predator
University of British Columbia researchers have uncovered the unique survival mechanisms of a marine organism that may be tiny, but in some ways has surpassed sharks in its predatory efficiency.
Published in the journal Nature Communications, the research team's portrait of the microscopic dinoflagellate Oxyrrhis marina reveals a predator so efficient that it has even acquired a gene from its prey.
"It's an interesting case of Lateral Gene Transfer, or the movement of genes between distantly related species," says Patrick Keeling, a UBC botany professor and one of the study's authors.
"Our study shows that Oxyrrhis marina has picked up a gene commonly used by marine bacteria for photosynthesis. Oxyrrhis probably got this gene by eating the bacteria, but the really interesting part is that the gene produces a protein called rhodopsin, which is a photoreceptor that can make energy from light."
Humans possess similar proteins in our eyes, called opsin, that enable vision in low-light conditions, but cannot produce energy.
"It is very much a case of 'you are what you eat,' because Oxyrrhis marina has so much rhodopsin in its system that it has assumed the protein's signature pink colour," says Keeling. "Our hypothesis is that it is using the rhodopsin to harvest energy from light - as bacteria often do - but we think that it also uses the energy to help digest its prey, some of which were the original supplier of the gene. It is a really neat mix of metabolic strategies."
Oxyrrhis marina is part of a family of marine plankton that also includes the organisms responsible for harmful red tides. It is common in shallow waters such as tide pools around the world, including along the British Columbia coast. It has evolved extreme survival mechanisms, including the ones described in the UBC study. Oxyrrhis marina can cannibalize its own species when no other prey is available.
"It definitely deserves to be called a predator - it can feed on cells almost as big as itself," says Keeling, director of the Centre for Microbial Diversity and Evolution and a member of Beaty Biodiversity Research Centre at UBC. "It is also extremely tough to kill it."
Source:
Brian Lin
University of British Columbia
Published in the journal Nature Communications, the research team's portrait of the microscopic dinoflagellate Oxyrrhis marina reveals a predator so efficient that it has even acquired a gene from its prey.
"It's an interesting case of Lateral Gene Transfer, or the movement of genes between distantly related species," says Patrick Keeling, a UBC botany professor and one of the study's authors.
"Our study shows that Oxyrrhis marina has picked up a gene commonly used by marine bacteria for photosynthesis. Oxyrrhis probably got this gene by eating the bacteria, but the really interesting part is that the gene produces a protein called rhodopsin, which is a photoreceptor that can make energy from light."
Humans possess similar proteins in our eyes, called opsin, that enable vision in low-light conditions, but cannot produce energy.
"It is very much a case of 'you are what you eat,' because Oxyrrhis marina has so much rhodopsin in its system that it has assumed the protein's signature pink colour," says Keeling. "Our hypothesis is that it is using the rhodopsin to harvest energy from light - as bacteria often do - but we think that it also uses the energy to help digest its prey, some of which were the original supplier of the gene. It is a really neat mix of metabolic strategies."
Oxyrrhis marina is part of a family of marine plankton that also includes the organisms responsible for harmful red tides. It is common in shallow waters such as tide pools around the world, including along the British Columbia coast. It has evolved extreme survival mechanisms, including the ones described in the UBC study. Oxyrrhis marina can cannibalize its own species when no other prey is available.
"It definitely deserves to be called a predator - it can feed on cells almost as big as itself," says Keeling, director of the Centre for Microbial Diversity and Evolution and a member of Beaty Biodiversity Research Centre at UBC. "It is also extremely tough to kill it."
Source:
Brian Lin
University of British Columbia
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