CORVALLIS, Ore. – Automobile owners around the world may some day soon be driving on tires that are partly made out of trees – which could cost less, perform better and save on fuel and energy.
Wood science researchers at Oregon State University have made some surprising findings about the potential of microcrystalline cellulose – a product that can be made easily from almost any type of plant fibers – to partially replace silica as a reinforcing filler in the manufacture of rubber tires.
A new study suggests that this approach might decrease the energy required to produce the tire, reduce costs, and better resist heat buildup. Early tests indicate that such products would have comparable traction on cold or wet pavement, be just as strong, and provide even higher fuel efficiency than traditional tires in hot weather.
"We were surprised at how favorable the results were for the use of this material," said Kaichang Li, an associate professor of wood science and engineering in the OSU College of Forestry, who conducted this research with graduate student Wen Bai.
"This could lead to a new generation of automotive tire technology, one of the first fundamental changes to come around in a long time," Li said.
Cellulose fiber has been used for some time as reinforcement in some types of rubber and automotive products, such as belts, hoses and insulation – but never in tires, where the preferred fillers are carbon black and silica. Carbon black, however, is made from increasingly expensive oil, and the processing of silica is energy-intensive. Both products are very dense and reduce the fuel efficiency of automobiles.
In the search for new types of reinforcing fillers that are inexpensive, easily available, light and renewable, OSU experts turned to microcrystalline cellulose – a micrometer-sized type of crystalline cellulose with an extremely well-organized structure. It is produced in a low-cost process of acid hydrolysis using nature's most abundant and sustainable natural polymer – cellulose – that comprises about 40-50 percent of wood.
In this study, OSU researchers replaced up to about 12 percent of the silica used in conventional tire manufacture. This decreased the amount of energy needed to compound the rubber composite, improved the heat resistance of the product, and retained tensile strength.
Traction is always a key issue with tire performance, and the study showed that the traction of the new product was comparable to existing rubber tire technology in a wet, rainy environment. However, at high temperatures such as in summer, the partial replacement of silica decreased the rolling resistance of the product, which would improve fuel efficiency of rubber tires made with the new approach.
More research is needed to confirm the long-term durability of tires made with partial replacement of silica, Li said. Further commercial development of this technology by a tire manufacturer could be undertaken at any time, he said. The newest findings were just published in a professional journal, Composites Part A: Applied Science and Manufacturing.
Tire manufacturing, a huge industry, could also provide another market for large amounts of Pacific Northwest natural fibers and the jobs and technology needed to process them
This advance is another in a series of significant discoveries in Li's research program at OSU in recent years. He developed a non-toxic adhesive for production of wood composite panels that has dramatically changed that industry, and in 2007 received a Presidential Green Chemistry Challenge Award at the National Academy of Sciences for his work on new, sustainable and environmentally friendly wood products.
Tuesday, July 21, 2009
A drug dispensing contact lens
Taking eye drops multiple times a day can be difficult for patients to do, and because of blinking and tearing, as little as 1 to 7 percent of the dose is actually absorbed by the eye. Now, researchers led by Daniel Kohane, MD, PhD, director of the Laboratory for Biomaterials and Drug Delivery at Children's Hospital Boston, have developed special contact lenses that can gradually dispense a constant amount of medication to the eye, at adjustable rates. They describe their prototype lens in the July issue of Investigative Ophthalmology and Visual Science.
Although other groups have developed drug-releasing contact lenses, none have been able to achieve a constant, steady release of substantial amounts of drug; typically, a burst of drug is delivered in the first few hours, followed by rapidly dwindling amounts that are too low to be therapeutic. Kohane, collaborator Joseph Ciolino, MD, of the Massachusetts Eye and Ear Infirmary, and colleagues at the Department of Chemical Engineering at the Massachusetts Institute of Technology (MIT) created a two-layer contact lens with an inner drug-bearing biodegradable polymer film known as PLGA. Both PLGA and pHEMA (used for the coating) have been well studied and are already approved for ocular use by the Food and Drug Administration.
In laboratory testing, the prototype lenses dispensed ciprofloxacin (an antibiotic often used in eyedrops) for 30 days, the longest duration for which contact lenses are currently approved by the FDA; in some tests, the lenses continued releasing drug for up to 100 days. The amounts dispensed were sufficient to kill pathogens in a laboratory assay.
Kohane and Ciolino see applications in conditions such as glaucoma and dry-eye which require frequent daily eye drops. They have begun to test the lens in animals and plan to begin human testing as soon as possible. The technology recently won the Life Sciences track in MIT's 100K Entrepreneurship Competition.
Although other groups have developed drug-releasing contact lenses, none have been able to achieve a constant, steady release of substantial amounts of drug; typically, a burst of drug is delivered in the first few hours, followed by rapidly dwindling amounts that are too low to be therapeutic. Kohane, collaborator Joseph Ciolino, MD, of the Massachusetts Eye and Ear Infirmary, and colleagues at the Department of Chemical Engineering at the Massachusetts Institute of Technology (MIT) created a two-layer contact lens with an inner drug-bearing biodegradable polymer film known as PLGA. Both PLGA and pHEMA (used for the coating) have been well studied and are already approved for ocular use by the Food and Drug Administration.
In laboratory testing, the prototype lenses dispensed ciprofloxacin (an antibiotic often used in eyedrops) for 30 days, the longest duration for which contact lenses are currently approved by the FDA; in some tests, the lenses continued releasing drug for up to 100 days. The amounts dispensed were sufficient to kill pathogens in a laboratory assay.
Kohane and Ciolino see applications in conditions such as glaucoma and dry-eye which require frequent daily eye drops. They have begun to test the lens in animals and plan to begin human testing as soon as possible. The technology recently won the Life Sciences track in MIT's 100K Entrepreneurship Competition.
Yale discovery may open door to drug that cuts appetite and boosts energy
In a major advance in obesity and diabetes research, Yale School of Medicine scientists have found that reducing levels of a key enzyme in the brain decreased appetites and increased energy levels.
Reductions in the levels of the enzyme prolylcarboxypeptidase (PRCP) led to weight loss and a decreased risk of type 2 diabetes in mice, according to research published in the August issue of the Journal of Clinical Investigation. The team found that PRCP is located in the hypothalamus and regulates levels of the alpha-melanocyte stimulating hormone (alpha-MSH), which is a peptide known for inhibiting food intake and stimulating energy expenditure. Researchers found that blocking the PRCP enzyme keeps the alpha-MSH peptides from being degraded, resulting in higher levels of alpha-MSH and decreased appetite.
"Our research provides the first evidence that breaking down molecules in the brain that regulate metabolism is an important component of weight control," said senior author Sabrina Diano, associate professor in the Departments of Obstetrics, Gynecology and Reproductive Sciences, and Neurobiology. "Our findings provide a possible new target for the development of drugs to control metabolic disorders such as obesity and type 2 diabetes."
Diano and her team conducted the study in congenic mice that were naturally lean and later in mice that had PRCP removed. Animals without the PRCP enzyme were leaner and ate less food. They also had higher levels of alpha-MSH in the hypothalamus compared to control animals. The mice were put on a diet of 45 percent fat—the equivalent of eating fast food everyday—and even with this high fat diet, they did not gain as much weight as control animals on a regular diet.
Diano said the next step is to study how PRCP is regulated.
Reductions in the levels of the enzyme prolylcarboxypeptidase (PRCP) led to weight loss and a decreased risk of type 2 diabetes in mice, according to research published in the August issue of the Journal of Clinical Investigation. The team found that PRCP is located in the hypothalamus and regulates levels of the alpha-melanocyte stimulating hormone (alpha-MSH), which is a peptide known for inhibiting food intake and stimulating energy expenditure. Researchers found that blocking the PRCP enzyme keeps the alpha-MSH peptides from being degraded, resulting in higher levels of alpha-MSH and decreased appetite.
"Our research provides the first evidence that breaking down molecules in the brain that regulate metabolism is an important component of weight control," said senior author Sabrina Diano, associate professor in the Departments of Obstetrics, Gynecology and Reproductive Sciences, and Neurobiology. "Our findings provide a possible new target for the development of drugs to control metabolic disorders such as obesity and type 2 diabetes."
Diano and her team conducted the study in congenic mice that were naturally lean and later in mice that had PRCP removed. Animals without the PRCP enzyme were leaner and ate less food. They also had higher levels of alpha-MSH in the hypothalamus compared to control animals. The mice were put on a diet of 45 percent fat—the equivalent of eating fast food everyday—and even with this high fat diet, they did not gain as much weight as control animals on a regular diet.
Diano said the next step is to study how PRCP is regulated.
Monday, July 20, 2009
New biosensor detects extremely low bacteria concentrations
Bacterial diseases are usually detected by first enriching samples, then separating, identifying, and counting the bacteria. This type of procedure usually takes at least two days after arrival of the sample in the laboratory. Tests that work faster, in the field, and without complex sample preparation, whilst being precise and error-free, are thus high on the wish list. A Spanish research team headed by Jordi Riu and F. Xavier Rius at the University Rovira i Virgili in Tarragona has now developed a new technique to make this wish come true. With a novel biosensor, they have been able to detect extremely low concentrations of the typhus-inducing Salmonella typhi. As reported in the journal Angewandte Chemie, their new method is based on electrochemical measurements by means of carbon nanotubes equipped with aptamers as bacteria-specific binding sites. If bacteria bind to the aptamers, the researchers detect a change in electrical voltage.
Aptamers are synthetic, short DNA or RNA strands that can be designed and made to bind a specific target molecule. An aptamer that specifically binds to salmonella has recently been developed. The Spanish researchers chose to use this aptamer for their biosensor. By means of additional functional groups, they securely anchored the aptamers to carbon nanotubes, which were deposited onto an electrode in an ultrathin layer.
In the absence of salmonella, the aptamers fit closely against the walls of the carbon nanotubes. If the biosensor is put into a salmonella-containing sample, the microbes stick to the aptamers like flies to flypaper. This influences the interaction between the aptamers and the nanotubes, which makes a change in the electrode voltage noticeable within seconds.
Using this biosensor, the researchers were able to detect a bacterial concentration equivalent to one salmonella bacterium in 5 mL of medium. Quantitative measurements were possible down to a concentration of about 1000 salmonella per milliliter. This biosensor is specific: it does not react to bacteria other than Salmonella typhi. "Our new technique makes the detection of micro-organisms as fast and simple as the measurement of pH value," say Riu and Rius.
Aptamers are synthetic, short DNA or RNA strands that can be designed and made to bind a specific target molecule. An aptamer that specifically binds to salmonella has recently been developed. The Spanish researchers chose to use this aptamer for their biosensor. By means of additional functional groups, they securely anchored the aptamers to carbon nanotubes, which were deposited onto an electrode in an ultrathin layer.
In the absence of salmonella, the aptamers fit closely against the walls of the carbon nanotubes. If the biosensor is put into a salmonella-containing sample, the microbes stick to the aptamers like flies to flypaper. This influences the interaction between the aptamers and the nanotubes, which makes a change in the electrode voltage noticeable within seconds.
Using this biosensor, the researchers were able to detect a bacterial concentration equivalent to one salmonella bacterium in 5 mL of medium. Quantitative measurements were possible down to a concentration of about 1000 salmonella per milliliter. This biosensor is specific: it does not react to bacteria other than Salmonella typhi. "Our new technique makes the detection of micro-organisms as fast and simple as the measurement of pH value," say Riu and Rius.
Common cold virus efficiently delivers corrected gene to cystic fibrosis cells
CHAPEL HILL – Scientists have worked for 20 years to perfect gene therapy for the treatment of cystic fibrosis, which causes the body to produce dehydrated, thicker-than-normal mucus that clogs the lungs and leads to life threatening infections.
Now University of North Carolina at Chapel Hill School of Medicine scientists have found what may be the most efficient way to deliver a corrected gene to lung cells collected from cystic fibrosis patients. They also showed that it may take this high level of efficiency for cystic fibrosis (CF) patients to see any benefit from gene therapy.
Using parainfluenza virus, one of the viruses that causes common colds, the UNC scientists found that delivery of a corrected version of the CFTR gene to 25 percent of cells grown in a tissue culture model that resembles the lining of the human airways was sufficient to restore normal function back to the tissue.
"This is the first demonstration in which we've been able to execute delivery in an efficient manner," said Ray Pickles, Ph.D., associate professor of microbiology and immunology at the UNC Cystic Fibrosis Research and Treatment Center. "When you consider that in past gene therapy studies, the targeting efficiency has been somewhere around 0.1 percent of cells, you can see this is a giant leap forward."
"We discovered that if you take a virus that has evolved to infect the human airways, and you engineer a normal CFTR gene into it, you can use this virus to correct all of the hallmark CF features in the model system that we used," Pickles said. For instance, the experiment improved the cells' ability to hydrate and transport mucus secretions.
The resulting paper is published in the July 21 issue of the journal PLoS Biology.
Now the researchers must work to ensure the safety of the delivery system. In a pleasant surprise, simply adding the CFTR gene to the virus significantly attenuated it, potentially reducing its ability to cause inflammation. But the scientists may need to alter the virus further.
"We haven't generated a vector that we can go out and give to patients now," Pickles said, "but these studies continue to convince us that a gene replacement therapy for CF patients will some day be available in the future."
Now University of North Carolina at Chapel Hill School of Medicine scientists have found what may be the most efficient way to deliver a corrected gene to lung cells collected from cystic fibrosis patients. They also showed that it may take this high level of efficiency for cystic fibrosis (CF) patients to see any benefit from gene therapy.
Using parainfluenza virus, one of the viruses that causes common colds, the UNC scientists found that delivery of a corrected version of the CFTR gene to 25 percent of cells grown in a tissue culture model that resembles the lining of the human airways was sufficient to restore normal function back to the tissue.
"This is the first demonstration in which we've been able to execute delivery in an efficient manner," said Ray Pickles, Ph.D., associate professor of microbiology and immunology at the UNC Cystic Fibrosis Research and Treatment Center. "When you consider that in past gene therapy studies, the targeting efficiency has been somewhere around 0.1 percent of cells, you can see this is a giant leap forward."
"We discovered that if you take a virus that has evolved to infect the human airways, and you engineer a normal CFTR gene into it, you can use this virus to correct all of the hallmark CF features in the model system that we used," Pickles said. For instance, the experiment improved the cells' ability to hydrate and transport mucus secretions.
The resulting paper is published in the July 21 issue of the journal PLoS Biology.
Now the researchers must work to ensure the safety of the delivery system. In a pleasant surprise, simply adding the CFTR gene to the virus significantly attenuated it, potentially reducing its ability to cause inflammation. But the scientists may need to alter the virus further.
"We haven't generated a vector that we can go out and give to patients now," Pickles said, "but these studies continue to convince us that a gene replacement therapy for CF patients will some day be available in the future."
Neural stem cells offer potential treatment for Alzheimer's disease
Irvine, Calif. – UC Irvine scientists have shown for the first time that neural stem cells can rescue memory in mice with advanced Alzheimer's disease, raising hopes of a potential treatment for the leading cause of elderly dementia that afflicts 5.3 million people in the U.S.
Mice genetically engineered to have Alzheimer's performed markedly better on memory tests a month after mouse neural stem cells were injected into their brains. The stem cells secreted a protein that created more neural connections, improving cognitive function.
"Essentially, the cells were producing fertilizer for the brain," said Frank LaFerla, director of UCI's Institute for Memory Impairments and Neurological Disorders, or UCI MIND, and co-author of the study, which appears online the week of July 20 in the Proceedings of the National Academy of Sciences.
Lead author Mathew Blurton-Jones, LaFerla and colleagues worked with older mice predisposed to develop brains lesions called plaques and tangles that are the hallmarks of Alzheimer's.
To learn how the stem cells worked, the scientists examined the mouse brains. To their surprise, they discovered that just 6 percent of the stem cells had turned into neurons. (The majority became the other two main types of brain cells, astrocytes and oligodendrocytes.) The stem cells didn't improve cognition by becoming new neurons, nor did they act by reducing the number of plaques and tangles.
Rather, the stem cells were found to have secreted a protein called brain-derived neurotrophic factor, or BDNF. This caused existing tissue to sprout new neurites, strengthening and increasing the number of connections between neurons. When the team selectively reduced BDNF from the stem cells, the benefit was lost, providing strong evidence that BDNF is critical to the effect of stem cells on memory and neuronal function.
"If you look at Alzheimer's, it's not the plaques and tangles that correlate best with dementia; it's the loss of synapses – connections between neurons," Blurton-Jones said. "The neural stem cells were helping the brain form new synapses and nursing the injured neurons back to health."
Diseased mice injected directly with BDNF also improved cognitively but not as much as with the neural stem cells, which provided a more long-term and consistent supply of the protein.
"This gives us a lot of hope that stem cells or a product from them, such as BDNF, will be a useful treatment for Alzheimer's," LaFerla said.
Mice genetically engineered to have Alzheimer's performed markedly better on memory tests a month after mouse neural stem cells were injected into their brains. The stem cells secreted a protein that created more neural connections, improving cognitive function.
"Essentially, the cells were producing fertilizer for the brain," said Frank LaFerla, director of UCI's Institute for Memory Impairments and Neurological Disorders, or UCI MIND, and co-author of the study, which appears online the week of July 20 in the Proceedings of the National Academy of Sciences.
Lead author Mathew Blurton-Jones, LaFerla and colleagues worked with older mice predisposed to develop brains lesions called plaques and tangles that are the hallmarks of Alzheimer's.
To learn how the stem cells worked, the scientists examined the mouse brains. To their surprise, they discovered that just 6 percent of the stem cells had turned into neurons. (The majority became the other two main types of brain cells, astrocytes and oligodendrocytes.) The stem cells didn't improve cognition by becoming new neurons, nor did they act by reducing the number of plaques and tangles.
Rather, the stem cells were found to have secreted a protein called brain-derived neurotrophic factor, or BDNF. This caused existing tissue to sprout new neurites, strengthening and increasing the number of connections between neurons. When the team selectively reduced BDNF from the stem cells, the benefit was lost, providing strong evidence that BDNF is critical to the effect of stem cells on memory and neuronal function.
"If you look at Alzheimer's, it's not the plaques and tangles that correlate best with dementia; it's the loss of synapses – connections between neurons," Blurton-Jones said. "The neural stem cells were helping the brain form new synapses and nursing the injured neurons back to health."
Diseased mice injected directly with BDNF also improved cognitively but not as much as with the neural stem cells, which provided a more long-term and consistent supply of the protein.
"This gives us a lot of hope that stem cells or a product from them, such as BDNF, will be a useful treatment for Alzheimer's," LaFerla said.
Protein structures revealed at record pace
BERKELEY, CA -- Scientists at the U.S. Department of Energy's (DOE) Lawrence Berkeley National Laboratory have developed a fast and efficient way to determine the structure of proteins, shortening a process that often takes years into a matter of days.
The high-throughput protein pipeline could allow scientists to expedite the development of biofuels, decipher how extremophiles thrive in conditions that kill most organisms, and better understand how proteins carry out life's vital functions.
The technique will help scientists keep pace with the growing flood of data stemming from genomic studies of organisms and environmental samples such as seawater and soil. Every new gene identified in these studies codes for a protein, and the structure of each protein must be characterized in order to determine what it does. Current structural characterization techniques are slow, however, meaning newly discovered proteins and their many complexes keep piling up, their function remaining a mystery.
"There's a bottleneck in structural genomics, and our system addresses that," says Greg Hura, a scientist in Berkeley Lab's Physical Biosciences Division. He developed the technique with John Tainer of Berkeley Lab's Life Sciences Division and the Scripps Research Institute in La Jolla, CA. Michael Adams and other scientists from the University of Georgia also contributed to the research.
Their work is published in the July 20 online edition of the journal Nature Methods.
The team developed the protein pipeline at the Advanced Light Source (ALS), a national user facility located at Berkeley Lab that generates intense light for scientific research. At a beamline called SIBYLS, they used a technique called small angle x-ray scattering (SAXS), which can image a protein in its natural state, such as in a solution, and at a spatial resolution of about 10 angstroms, which is small enough to determine a protein's three-dimensional shape. The brilliant light generated by the Advanced Light Source minimizes the amount of material required for each experiment, which makes the technique practical for almost any biomolecule.
To maximize speed, Hura installed a robot that automatically pipettes protein samples into position so they can be analyzed by x-ray scattering. And to analyze the resulting data, they used the supercomputing resources of the U.S. Department of Energy's National Energy Research Scientific Computing Center (NERSC), which is based at Berkeley Lab. The supercomputer's clusters can churn through data for 20 proteins per week, or more than 1000 macromolecules per year.
The result is a system that moves at breakneck speed compared to current techniques used to determine the shape and structure of proteins: x-ray crystallography and nuclear magnetic resonance. Recently, in the span of one month, the team used the system to resolve the structure of 40 proteins from Pyrococcus furiosus, a microscopic extremophile that can live at 100°C.
"This would have taken several years with x-ray crystallography," says Hura. "What used to take years, now can takes weeks."
Adds Tainer, "We can now obtain structural information in solution on most samples, rather than the 15 percent obtained by the best of the current Structural Genomics Initiative efforts employing nuclear magnetic resonance and crystallography. "
The Berkeley Lab team chose P. furiosus because it is an intriguing candidate for the production of clean energy and other applications. It has a pathway that produces hydrogen, which is a potential alternative fuel. And many industrial processes are highly acidic and very hot — conditions that P. furiosus loves.
"If we could learn which of the organism's proteins allow it to thrive in these conditions, then maybe we can apply them to energy production and other applications," says Hura.
Future synthetic biology efforts may involve taking a useful protein or a network of proteins from one microbe, and importing it into another microbe. In order to do this, scientists must learn how much of the network needs to be imported and still have it be able to do its job. This requires analyzing individual proteins in hundreds of different conditions.
"This is where our system will have a big impact. We can do this type of structural analysis in a matter of weeks, as opposed to years with crystallography," says Hura.
Of course, such speed doesn't come without tradeoffs. X-ray crystallography yields extremely high-resolution images, while small angle x-ray scattering yields a protein's shape at a much lower resolution of about 10 angstroms (one angstrom is one ten-millionth of a millimeter).
But the level of information offered by x-ray crystallography isn't always necessary. Sometimes, simply knowing if one protein is similar in shape to another is enough to learn its function. And SAXS makes up for what it lacks in precision by providing accurate information on the shape, assembly, and conformational changes of proteins in solution.
"We can have less information and still answer the questions that need to be answered," says Hura, adding that their technique will help usher in the next phase of genomics research. "The number of genes being identified is growing at a huge rate. We need to keep pace with this and learn about all the proteins encoded in these genes."
Adds Tainer, "This pipeline is an example of the stunning impact we can achieve by combining physics and engineering with structural biology, which is possible at government labs like Berkeley Lab."
The high-throughput protein pipeline could allow scientists to expedite the development of biofuels, decipher how extremophiles thrive in conditions that kill most organisms, and better understand how proteins carry out life's vital functions.
The technique will help scientists keep pace with the growing flood of data stemming from genomic studies of organisms and environmental samples such as seawater and soil. Every new gene identified in these studies codes for a protein, and the structure of each protein must be characterized in order to determine what it does. Current structural characterization techniques are slow, however, meaning newly discovered proteins and their many complexes keep piling up, their function remaining a mystery.
"There's a bottleneck in structural genomics, and our system addresses that," says Greg Hura, a scientist in Berkeley Lab's Physical Biosciences Division. He developed the technique with John Tainer of Berkeley Lab's Life Sciences Division and the Scripps Research Institute in La Jolla, CA. Michael Adams and other scientists from the University of Georgia also contributed to the research.
Their work is published in the July 20 online edition of the journal Nature Methods.
The team developed the protein pipeline at the Advanced Light Source (ALS), a national user facility located at Berkeley Lab that generates intense light for scientific research. At a beamline called SIBYLS, they used a technique called small angle x-ray scattering (SAXS), which can image a protein in its natural state, such as in a solution, and at a spatial resolution of about 10 angstroms, which is small enough to determine a protein's three-dimensional shape. The brilliant light generated by the Advanced Light Source minimizes the amount of material required for each experiment, which makes the technique practical for almost any biomolecule.
To maximize speed, Hura installed a robot that automatically pipettes protein samples into position so they can be analyzed by x-ray scattering. And to analyze the resulting data, they used the supercomputing resources of the U.S. Department of Energy's National Energy Research Scientific Computing Center (NERSC), which is based at Berkeley Lab. The supercomputer's clusters can churn through data for 20 proteins per week, or more than 1000 macromolecules per year.
The result is a system that moves at breakneck speed compared to current techniques used to determine the shape and structure of proteins: x-ray crystallography and nuclear magnetic resonance. Recently, in the span of one month, the team used the system to resolve the structure of 40 proteins from Pyrococcus furiosus, a microscopic extremophile that can live at 100°C.
"This would have taken several years with x-ray crystallography," says Hura. "What used to take years, now can takes weeks."
Adds Tainer, "We can now obtain structural information in solution on most samples, rather than the 15 percent obtained by the best of the current Structural Genomics Initiative efforts employing nuclear magnetic resonance and crystallography. "
The Berkeley Lab team chose P. furiosus because it is an intriguing candidate for the production of clean energy and other applications. It has a pathway that produces hydrogen, which is a potential alternative fuel. And many industrial processes are highly acidic and very hot — conditions that P. furiosus loves.
"If we could learn which of the organism's proteins allow it to thrive in these conditions, then maybe we can apply them to energy production and other applications," says Hura.
Future synthetic biology efforts may involve taking a useful protein or a network of proteins from one microbe, and importing it into another microbe. In order to do this, scientists must learn how much of the network needs to be imported and still have it be able to do its job. This requires analyzing individual proteins in hundreds of different conditions.
"This is where our system will have a big impact. We can do this type of structural analysis in a matter of weeks, as opposed to years with crystallography," says Hura.
Of course, such speed doesn't come without tradeoffs. X-ray crystallography yields extremely high-resolution images, while small angle x-ray scattering yields a protein's shape at a much lower resolution of about 10 angstroms (one angstrom is one ten-millionth of a millimeter).
But the level of information offered by x-ray crystallography isn't always necessary. Sometimes, simply knowing if one protein is similar in shape to another is enough to learn its function. And SAXS makes up for what it lacks in precision by providing accurate information on the shape, assembly, and conformational changes of proteins in solution.
"We can have less information and still answer the questions that need to be answered," says Hura, adding that their technique will help usher in the next phase of genomics research. "The number of genes being identified is growing at a huge rate. We need to keep pace with this and learn about all the proteins encoded in these genes."
Adds Tainer, "This pipeline is an example of the stunning impact we can achieve by combining physics and engineering with structural biology, which is possible at government labs like Berkeley Lab."
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