Come summer, we will once again marvel at the amazing athletic skills of Olympic athletes while in fact, the simple act of walking is no less remarkable. Just to prevent us from toppling over, the neuromuscular circuitry that controls all bodily movements relies on constant sensory feedback from the periphery to fine-tune its commands to hundreds of muscles.
But it still remains unclear, how during embryonic development, sensory and motor neurons become incorporated into tightly coordinated pathways without getting mixed up. In a study, published in the current issue of Science, scientists at the Salk Institute for Biological Studies report that constant crosstalk between growing sensory and motor neurons keeps them on track.
Skeletal muscle consists of thousands of muscle fibers, each controlled by one motor neuron in the spinal cord that connects to individual muscle fibers and relays signals from the brain. Sensory stretch receptors, which are located in most muscles, as well as temperature, pressure and pain receptors, all send information back to the central nervous system.
"If you look at a cross section of a nerve bundle it really is a mix of wires. Some wires are sending signals out from the spinal cord and others are sending signals to the spinal cord," explains Samuel Pfaff, Ph.D, a professor in the Gene Expression Laboratory, who together with former post doctoral fellow Till Marquardt, Ph.D., now a group leader at the European Neuroscience Institute in Göttingen, directed the study. "The motor and sensory nerves are not unlike a roadway with orderly traffic moving in both directions by staying in its proper lanes," he adds.
During embryonic development, nerve cells hesitantly extend tentacle-like protrusions called axons. Growth cones, small enlargements at the axons tip actively search their local environment for chemical cues that guide them to their target. One such cue comes from a class of molecules called ephrins, which repel cells carrying Eph proteins, gently nudging them in the right direction.
The traditional view was that growth cones studded with Eph proteins, which take on the role of receptors, search their environments for ephrins, which take on the role of ligands. During his time as a postdoctoral researcher in Pfaff's laboratory, Marquardt discovered that neurons not only carry both types of proteins, but that the role of ephrins and Ephs can change as well.
"The fact that neurons can express receptors and ligands and that everything can be a receptor or ligand, raised the question what happens when you have two neurons that grow beside each other and occasionally bump into one another," says Pfaff. To answer the question, the Salk researchers settled on sensory and motor neurons, which extend their axons along the same pathway to the periphery.
First, co-first authors Benjamin W. Gallarda, and Dario Bonanomi, Ph.D., generated mice that allowed them to genetically distinguish between sensory and motor neurons with different "labels". With ephrin/Eph signaling intact, their axons joined up after they emerged from the spinal cord but sorted into separate fascicles containing either sensory or motor axons, but never both. When the researchers deleted EphA3 and EphA4 in motor neurons, interrupting the cross talk across the highway divide, things started to go severely wrong.
The sorting between the fascicles of the motor and sensory axons broke down and instead of reaching for muscles, some motor neurons left their lane, made a U-turn, joined the sensory lane and headed back toward the spinal cord. "It was a real wiring disaster," says Pfaff. "It appears that ephrin and Eph not only control the decision where these axons grow out in the periphery but also maintain the normal arrangement between the motor and sensory pathway."
The ephrin/Eph tag team not only helps the body's motor nerve cells grow along their proper paths during embryonic development, it also plays a major role in preventing spinal cord neurons from regenerating after injuries. Hoping to coax injured neurons into rewiring severed connections, researchers in the spinal cord field are hard at work trying to overcome the block that prevents axonal growth within the central nervous system.
"Our findings emphasize that this needs to be done cautiously. If you promote indiscriminate motor axon growth it could cause a lot of problems," cautions Pfaff. "There are many examples of extensive neuronal reorganization following spinal cord injuries and one often underappreciated byproduct is severe pain."
Researchers who also contributed to the study include Daniel MГјller, Ph.D., a post-doctoral researcher in the Marquardt laboratory, Arthur Brown, Ph.D., associate professor at the University of Western Ontario, Canada, postdoctoral researchers William A. Alaynick, Ph.D., Shane E. Andrews, Ph.D., both in the Pfaff laboratory, and Greg Lemke, professor in the Molecular Neurobiology Laboratory at the Salk.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.
Source: Gina Kirchweger
Salk Institute
суббота, 21 мая 2011 г.
New Wisconsin Center Of Excellence In Genomics Science Established By The NIH National Genome Research Institute
The National Human Genome Research Institute (NHGRI) of the National Institutes of Health today announced an $8 million, three-year grant to establish a Wisconsin Center of Excellence in Genomics Science. The new Center is a collaborative effort between the University of Wisconsin in Madison, The Medical College of Wisconsin, and Marquette University, and will be coordinated by the Medical College of Wisconsin. It will be co-directed by Michael Olivier, Ph.D., professor of physiology at the MCW Biotechnology and Bioengineering Center (BBC) and the Human and Molecular Genetics Center (HMGC); and Lloyd M. Smith, Ph.D., W.L. Hubbell professor of chemistry and Director of the Genome Center of Wisconsin (GCW) at UW-Madison.
The Centers of Excellence in Genomics Science program, initiated by NHGRI in 2001, assembles interdisciplinary research teams to develop novel technologies that significantly advance genomic research. The Wisconsin Center and another newly funded Center of Excellence at the University of North Carolina join an elite group of existing Centers of Excellence at Arizona State University, the California Institute of Technology, the Dana Farber Cancer Institute, Harvard University, Johns Hopkins University, Stanford University, the University of Southern California, and Yale University.
"Our aim is to foster the formation of innovative research teams that will develop genomic tools and technologies that help to advance human health," said Alan E. Guttmacher, M.D., NHGRI's acting director. "Each of these centers is in a position to tackle some of the most challenging questions facing biology today."
The team at the Wisconsin Center will focus on developing novel technologies for the comprehensive analysis of proteins that bind to DNA. According to Dr. Olivier, "We have a complete blueprint of the human DNA sequence thanks to the Human Genome Project, but we still do not really understand how the information encoded in the genome is read and used by the millions of cells in our body. Recent development of novel technologies allows us to study how individual proteins bind and interact with the DNA across the entire genome, and how this interaction varies in different cell types and under different conditions. Unfortunately, this approach only works with proteins that are already known. What is needed, and what we will develop in this Center, is technology that is able to identify all of the proteins that are interacting with the genome, even if we do not know in advance what their function may be."
According to Dr. Smith, "We want to know what sets of genes are turned on and off, and how this is coordinated and controlled. We have DNA sequences for so many organisms, but the big question now is figuring out what they are doing. We have the blueprints, but we don't know how to read them, and gene regulation is front and center to that problem. Can we find the rules for when genes are turned on and off?"
Rather than using the traditional approach of identifying the DNA sequences where regulatory factors bind, the Center will develop novel technologies that identify the proteins that bind to particular DNA regions. Through this approach, investigators may be able to identify entirely new regulatory proteins. The researchers' ultimate goal is to develop a toolbox that can be used to better understand the relationship between changes in protein-DNA interactions and the underlying complex machinery controlling genes. Their approach combines DNA chip technology with very powerful and highly sensitive new instruments for identifying proteins.
"When we figure that out, we can use the information to understand what the rules are; without this information, we are flying blind," says Dr. Smith.
The work of the new Center builds on a long-standing collaboration between the groups at the Medical College and UW-Madison as part of their joint NIH-supported National Center of Proteomics Research. The new Wisconsin Center of Excellence builds on the existing strength in areas such as proteomics, genomics, chemistry, and bioinformatics, especially at the Biotechnology and Bioengineering Center at MCW and the Genome Center of Wisconsin at UW-Madison.
In addition to Drs Olivier and Smith, the Center of Excellence includes Dr. Lisa Cirillo, associate professor of cell biology, neurobiology and anatomy (MCW), Dr. Joshua Coon, associate professor of chemistry (UW Madison), Dr. Steven Duncan, the Marcus Professor of Human and Molecular Genetics (MCW), Dr. Melinda Dwinell, assistant professor of physiology at the HMGC (MCW), Dr. Audrey Gasch, assistant professor of genetics and GCW Member (UW-Madison), Dr. Andrew Greene, professor of physiology and director of the BBC (MCW), Dr. Jozef Lazar, associate professor of dermatology at the HMGC (MCW), Dr. Mingyu Liang, associate professor of physiology (MCW), Dr. Shama Mirza, assistant professor of biochemistry at the BBC (MCW), Dr. Craig Struble, associate professor of mathematics, statistics, and computer science (Marquette University), Dr. Scott Terhune, assistant professor of microbiology and molecular genetics at the BBC (MCW), Dr. James Thomson, professor of anatomy and GCW Member (UW Madison), and Dr. Simon Twigger, assistant professor of physiology at the BBC (MCW).
Source:
Toranj Marphetia
Medical College of Wisconsin
The Centers of Excellence in Genomics Science program, initiated by NHGRI in 2001, assembles interdisciplinary research teams to develop novel technologies that significantly advance genomic research. The Wisconsin Center and another newly funded Center of Excellence at the University of North Carolina join an elite group of existing Centers of Excellence at Arizona State University, the California Institute of Technology, the Dana Farber Cancer Institute, Harvard University, Johns Hopkins University, Stanford University, the University of Southern California, and Yale University.
"Our aim is to foster the formation of innovative research teams that will develop genomic tools and technologies that help to advance human health," said Alan E. Guttmacher, M.D., NHGRI's acting director. "Each of these centers is in a position to tackle some of the most challenging questions facing biology today."
The team at the Wisconsin Center will focus on developing novel technologies for the comprehensive analysis of proteins that bind to DNA. According to Dr. Olivier, "We have a complete blueprint of the human DNA sequence thanks to the Human Genome Project, but we still do not really understand how the information encoded in the genome is read and used by the millions of cells in our body. Recent development of novel technologies allows us to study how individual proteins bind and interact with the DNA across the entire genome, and how this interaction varies in different cell types and under different conditions. Unfortunately, this approach only works with proteins that are already known. What is needed, and what we will develop in this Center, is technology that is able to identify all of the proteins that are interacting with the genome, even if we do not know in advance what their function may be."
According to Dr. Smith, "We want to know what sets of genes are turned on and off, and how this is coordinated and controlled. We have DNA sequences for so many organisms, but the big question now is figuring out what they are doing. We have the blueprints, but we don't know how to read them, and gene regulation is front and center to that problem. Can we find the rules for when genes are turned on and off?"
Rather than using the traditional approach of identifying the DNA sequences where regulatory factors bind, the Center will develop novel technologies that identify the proteins that bind to particular DNA regions. Through this approach, investigators may be able to identify entirely new regulatory proteins. The researchers' ultimate goal is to develop a toolbox that can be used to better understand the relationship between changes in protein-DNA interactions and the underlying complex machinery controlling genes. Their approach combines DNA chip technology with very powerful and highly sensitive new instruments for identifying proteins.
"When we figure that out, we can use the information to understand what the rules are; without this information, we are flying blind," says Dr. Smith.
The work of the new Center builds on a long-standing collaboration between the groups at the Medical College and UW-Madison as part of their joint NIH-supported National Center of Proteomics Research. The new Wisconsin Center of Excellence builds on the existing strength in areas such as proteomics, genomics, chemistry, and bioinformatics, especially at the Biotechnology and Bioengineering Center at MCW and the Genome Center of Wisconsin at UW-Madison.
In addition to Drs Olivier and Smith, the Center of Excellence includes Dr. Lisa Cirillo, associate professor of cell biology, neurobiology and anatomy (MCW), Dr. Joshua Coon, associate professor of chemistry (UW Madison), Dr. Steven Duncan, the Marcus Professor of Human and Molecular Genetics (MCW), Dr. Melinda Dwinell, assistant professor of physiology at the HMGC (MCW), Dr. Audrey Gasch, assistant professor of genetics and GCW Member (UW-Madison), Dr. Andrew Greene, professor of physiology and director of the BBC (MCW), Dr. Jozef Lazar, associate professor of dermatology at the HMGC (MCW), Dr. Mingyu Liang, associate professor of physiology (MCW), Dr. Shama Mirza, assistant professor of biochemistry at the BBC (MCW), Dr. Craig Struble, associate professor of mathematics, statistics, and computer science (Marquette University), Dr. Scott Terhune, assistant professor of microbiology and molecular genetics at the BBC (MCW), Dr. James Thomson, professor of anatomy and GCW Member (UW Madison), and Dr. Simon Twigger, assistant professor of physiology at the BBC (MCW).
Source:
Toranj Marphetia
Medical College of Wisconsin
Thermochemical Nanolithography Now Allows Multiple Chemicals On A Chip
Scientists at Georgia Tech have developed a nanolithographic technique that can produce high-resolution patterns of at least three different chemicals on a single chip at writing speeds of up to one millimeter per second. The chemical nanopatterns can be tailor-designed with any desired shape and have been shown to be sufficiently stable so that they can be stored for weeks and then used elsewhere. The technique, known as Thermochemical Nanolithography is detailed in the December 2009 edition of the journal Advanced Functional Materials. The research has applications in a number of scientific fields from electronics to medicine.
"The strength of this method is really the possibility to produce low-cost, high-resolution and high-density chemical patterns on a sample that can be delivered in any lab around the world, where even non experts in nanotechnology can dip the sample in the desired solution and, for example, make nano-arrays of proteins, DNA or nanoparticles," said Elisa Riedo, associate professor in the School of Physics at the Georgia Institute of Technology.
Conceptually, the technique is surprisingly simple. Using an atomic force microscope (AFM), researchers heat a silicon tip and run it over a thin polymer film. The heat from the tip induces a local chemical reaction at the surface of the film. This reaction changes the film's chemical reactivity and transforms it from an inert surface to a reactive one that can selectively attach other molecules. The team first developed the technique in 2007. Now they've added some important new twists that should make thermochemical nanolithography (TCNL) an extremely useful tool for scientists working at the nanoscale.
"We've created a way to make independent patterns of multiple chemicals on a chip that can be drawn in whatever shape you want," said Jennifer Curtis, assistant professor in the School of Physics.
Being able to create high-resolution features of different chemicals in arbitrary shapes is important because some nanolithography techniques are limited to just one chemistry, lower resolutions and/or fixed shapes. In addition, TCNL's speed capability of one millimeter per second makes it orders of magnitude faster than the widely used dip-pen nanolithography, which routinely clocks at a speed of 0.0001 millimeters per second per pen.
The research is enabled by heated AFM probe tips that can create a hot spot as small as a few nanometers in diameter. Such tips are designed and fabricated by collaborator Professor William King at the University of Illinois, Urbana-Champaign. "The heated tip allows one to direct nano-scale chemical reactions," said King.
The new technique produces multiple chemical patterns on the same chip by using the AFM to heat a polymer film and change its reactivity. The chip is then dipped into a solution, which allows chemicals (for example, proteins or other chemical linkers) in the solution to bind to the chip on the parts where it has been heated. The AFM then heats the film in another spot. The chip is dipped into another solution and again another chemical can bind to the chip.
In the paper, the scientists show they can pattern amine, thiol, aldehyde and biotin using this technique. But in principle TCNL could be used for almost any chemical. Their work also shows that the chemical patterns can be used to organize functional materials at the surface, such as proteins and DNA.
"The power of this technique is that in principle it can work with almost any chemical or chemically reactive nano-object. It allows scientists to very rapidly draw many things that can then be converted to any number of different things, which themselves can bind selectively to yet any number of other things. So, it doesn't matter if you're interested in biology, electronics, medicine or chemistry, TCNL can create the reactive pattern to bind what you choose," said Seth Marder, professor in Tech's School of Chemistry and Biochemistry and director of the Center for Organic Photonics and Electronics.
In addition, TCNL allows the chemical writing to be done in one location with the nano-object patterning in another, so that scientists who aren't experts in writing chemical patterns on the nanoscale can still attach their objects to it. It's the technique's stability that makes this possible.
"Once you draw the pattern, it's very stable and non-reactive. We've shown that you can have it for more than a month, take it out and dip it and it still will bind," said Riedo.
"I would like to think that several years from now people will have access to a TCNL tool that enables them to do this patterning at a place like Georgia Tech, that's much less expensive than the kind of nanolithography tools we currently use in our clean room," said Marder.
The research was supported by the National Science Foundation, the U.S. Department of Energy, the Georgia Institute of Technology, GT Innovative Award, and ONR Nanoelectronics.
Source: David Terraso
Georgia Institute of Technology
"The strength of this method is really the possibility to produce low-cost, high-resolution and high-density chemical patterns on a sample that can be delivered in any lab around the world, where even non experts in nanotechnology can dip the sample in the desired solution and, for example, make nano-arrays of proteins, DNA or nanoparticles," said Elisa Riedo, associate professor in the School of Physics at the Georgia Institute of Technology.
Conceptually, the technique is surprisingly simple. Using an atomic force microscope (AFM), researchers heat a silicon tip and run it over a thin polymer film. The heat from the tip induces a local chemical reaction at the surface of the film. This reaction changes the film's chemical reactivity and transforms it from an inert surface to a reactive one that can selectively attach other molecules. The team first developed the technique in 2007. Now they've added some important new twists that should make thermochemical nanolithography (TCNL) an extremely useful tool for scientists working at the nanoscale.
"We've created a way to make independent patterns of multiple chemicals on a chip that can be drawn in whatever shape you want," said Jennifer Curtis, assistant professor in the School of Physics.
Being able to create high-resolution features of different chemicals in arbitrary shapes is important because some nanolithography techniques are limited to just one chemistry, lower resolutions and/or fixed shapes. In addition, TCNL's speed capability of one millimeter per second makes it orders of magnitude faster than the widely used dip-pen nanolithography, which routinely clocks at a speed of 0.0001 millimeters per second per pen.
The research is enabled by heated AFM probe tips that can create a hot spot as small as a few nanometers in diameter. Such tips are designed and fabricated by collaborator Professor William King at the University of Illinois, Urbana-Champaign. "The heated tip allows one to direct nano-scale chemical reactions," said King.
The new technique produces multiple chemical patterns on the same chip by using the AFM to heat a polymer film and change its reactivity. The chip is then dipped into a solution, which allows chemicals (for example, proteins or other chemical linkers) in the solution to bind to the chip on the parts where it has been heated. The AFM then heats the film in another spot. The chip is dipped into another solution and again another chemical can bind to the chip.
In the paper, the scientists show they can pattern amine, thiol, aldehyde and biotin using this technique. But in principle TCNL could be used for almost any chemical. Their work also shows that the chemical patterns can be used to organize functional materials at the surface, such as proteins and DNA.
"The power of this technique is that in principle it can work with almost any chemical or chemically reactive nano-object. It allows scientists to very rapidly draw many things that can then be converted to any number of different things, which themselves can bind selectively to yet any number of other things. So, it doesn't matter if you're interested in biology, electronics, medicine or chemistry, TCNL can create the reactive pattern to bind what you choose," said Seth Marder, professor in Tech's School of Chemistry and Biochemistry and director of the Center for Organic Photonics and Electronics.
In addition, TCNL allows the chemical writing to be done in one location with the nano-object patterning in another, so that scientists who aren't experts in writing chemical patterns on the nanoscale can still attach their objects to it. It's the technique's stability that makes this possible.
"Once you draw the pattern, it's very stable and non-reactive. We've shown that you can have it for more than a month, take it out and dip it and it still will bind," said Riedo.
"I would like to think that several years from now people will have access to a TCNL tool that enables them to do this patterning at a place like Georgia Tech, that's much less expensive than the kind of nanolithography tools we currently use in our clean room," said Marder.
The research was supported by the National Science Foundation, the U.S. Department of Energy, the Georgia Institute of Technology, GT Innovative Award, and ONR Nanoelectronics.
Source: David Terraso
Georgia Institute of Technology
American Chemical Society, Portico Sign Agreement For Permanent Electronic Archiving Of ACS Content
The American Chemical Society (ACS) Publications Division has signed a major archiving agreement with Portico, a not-for-profit organization whose mission is to preserve scholarly literature published in electronic form and to ensure that these materials remain accessible to future scholars, researchers and students.
Portico's electronic archiving service was launched in 2005 with support provided by The Andrew W. Mellon Foundation, Ithaka, The Library of Congress and Journal Storage (JSTOR). The agreement assures long-term preservation and ongoing access to electronic content from the journals of the ACS.
With the signing of this agreement, ACS joins a growing body of publishers - currently numbering more than 30 and encompassing over 6,000 titles - who have entrusted Portico to provide a permanent archive of their journal content, thus enabling libraries to migrate more quickly to electronic resources without risking future accessibility.
Robert D. Bovenschulte, President of ACS Publications, commented on the Portico agreement: "The archiving and preservation of our digital content is a key strategic priority for ACS Publications. We are delighted to be partnering with Portico as an important part of our solution to ensure permanent and ongoing access to our essential research in the chemical and related sciences. As our institutional customers and ACS members increasingly rely on electronic content for their scholarly research, they can be assured of ACS Publications' commitment to safeguarding electronic access to our journal content for the future."
Eileen Fenton, Executive Director of Portico, commented: "We are very pleased that the electronic content of the American Chemical Society will be added to the Portico archive. As electronic journals have become a vital part of the scholarly record, the need for robust, multi-layered archival arrangements has become more urgent. We look forward to incorporating ACS journal content into Portico's active archive operations, and are delighted to serve as the secure repository of this portion of the scholarly record."
The Portico archiving agreement complements ACS's participation in the Controlled Lots of Copies Keep Stuff Safe (CLOCKSS) program, which ACS joined in the spring of 2006. CLOCKSS is a preservation initiative between publishers, libraries and the Online Computer Library Center (OCLC).
The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio. The ACS Publications Division currently publishes 35 leading peer-reviewed journals in the chemical and related sciences, including the Journal of the American Chemical Society, as well as Chemical & Engineering News, the Society's weekly news magazine.
Contact: Michael Bernstein
American Chemical Society
Portico's electronic archiving service was launched in 2005 with support provided by The Andrew W. Mellon Foundation, Ithaka, The Library of Congress and Journal Storage (JSTOR). The agreement assures long-term preservation and ongoing access to electronic content from the journals of the ACS.
With the signing of this agreement, ACS joins a growing body of publishers - currently numbering more than 30 and encompassing over 6,000 titles - who have entrusted Portico to provide a permanent archive of their journal content, thus enabling libraries to migrate more quickly to electronic resources without risking future accessibility.
Robert D. Bovenschulte, President of ACS Publications, commented on the Portico agreement: "The archiving and preservation of our digital content is a key strategic priority for ACS Publications. We are delighted to be partnering with Portico as an important part of our solution to ensure permanent and ongoing access to our essential research in the chemical and related sciences. As our institutional customers and ACS members increasingly rely on electronic content for their scholarly research, they can be assured of ACS Publications' commitment to safeguarding electronic access to our journal content for the future."
Eileen Fenton, Executive Director of Portico, commented: "We are very pleased that the electronic content of the American Chemical Society will be added to the Portico archive. As electronic journals have become a vital part of the scholarly record, the need for robust, multi-layered archival arrangements has become more urgent. We look forward to incorporating ACS journal content into Portico's active archive operations, and are delighted to serve as the secure repository of this portion of the scholarly record."
The Portico archiving agreement complements ACS's participation in the Controlled Lots of Copies Keep Stuff Safe (CLOCKSS) program, which ACS joined in the spring of 2006. CLOCKSS is a preservation initiative between publishers, libraries and the Online Computer Library Center (OCLC).
The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio. The ACS Publications Division currently publishes 35 leading peer-reviewed journals in the chemical and related sciences, including the Journal of the American Chemical Society, as well as Chemical & Engineering News, the Society's weekly news magazine.
Contact: Michael Bernstein
American Chemical Society
DNA Could Be Backbone Of Next Generation Logic Chips
In a single day, a solitary grad student at a lab bench can produce more simple logic circuits than the world's entire output of silicon chips in a month.
So says a Duke University engineer, who believes that the next generation of these logic circuits at the heart of computers will be produced inexpensively in almost limitless quantities. The secret is that instead of silicon chips serving as the platform for electric circuits, computer engineers will take advantage of the unique properties of DNA, that double-helix carrier of all life's information.
In his latest set of experiments, Chris Dwyer, assistant professor of electrical and computer engineering at Duke's Pratt School of Engineering, demonstrated that by simply mixing customized snippets of DNA and other molecules, he could create literally billions of identical, tiny, waffle-looking structures.
Dwyer has shown that these nanostructures will efficiently self-assemble, and when different light-sensitive molecules are added to the mixture, the waffles exhibit unique and "programmable" properties that can be readily tapped. Using light to excite these molecules, known as chromophores, he can create simple logic gates, or switches.
These nanostructures can then be used as the building blocks for a variety of applications, ranging from the biomedical to the computational.
"When light is shined on the chromophores, they absorb it, exciting the electrons," Dwyer said. "The energy released passes to a different type of chromophore nearby that absorbs the energy and then emits light of a different wavelength. That difference means this output light can be easily differentiated from the input light, using a detector."
Instead of conventional circuits using electrical current to rapidly switch between zeros or ones, or to yes and no, light can be used to stimulate similar responses from the DNA-based switches - and much faster.
"This is the first demonstration of such an active and rapid processing and sensing capacity at the molecular level," Dwyer said. The results of his experiments were published online in the journal Small. "Conventional technology has reached its physical limits. The ability to cheaply produce virtually unlimited supplies of these tiny circuits seems to me to be the next logical step."
DNA is a well-understood molecule made up of pairs of complimentary nucleotide bases that have an affinity for each other. Customized snippets of DNA can cheaply be synthesized by putting the pairs in any order. In their experiments, the researchers took advantage of DNA's natural ability to latch onto corresponding and specific areas of other DNA snippets.
Dwyer used a jigsaw puzzle analogy to describe the process of what happens when all the waffle ingredients are mixed together in a container.
"It's like taking pieces of a puzzle, throwing them in a box and as you shake the box, the pieces gradually find their neighbors to form the puzzle," he said. "What we did was to take billions of these puzzle pieces, throwing them together, to form billions of copies of the same puzzle."
In the current experiments, the waffle puzzle had 16 pieces, with the chromophores located atop the waffle's ridges. More complex circuits can be created by building structures composed of many of these small components, or by building larger waffles. The possibilities are limitless, Dwyer said.
In addition to their use in computing, Dwyer said that since these nanostructures are basically sensors, many biomedical applications are possible. Tiny nanostructures could be built that could respond to different proteins that are markers for disease in a single drop of blood.
Dwyer's research is supported by the National Science Foundation, the Air Force Research Laboratory, the Defense Advanced Research Projects Agency and the Army Research Office. Other members of the Duke team were Constantin Pistol, Vincent Mao, Viresh Thusu and Alvin Lebeck.
Source:
Richard Merritt
Duke University
So says a Duke University engineer, who believes that the next generation of these logic circuits at the heart of computers will be produced inexpensively in almost limitless quantities. The secret is that instead of silicon chips serving as the platform for electric circuits, computer engineers will take advantage of the unique properties of DNA, that double-helix carrier of all life's information.
In his latest set of experiments, Chris Dwyer, assistant professor of electrical and computer engineering at Duke's Pratt School of Engineering, demonstrated that by simply mixing customized snippets of DNA and other molecules, he could create literally billions of identical, tiny, waffle-looking structures.
Dwyer has shown that these nanostructures will efficiently self-assemble, and when different light-sensitive molecules are added to the mixture, the waffles exhibit unique and "programmable" properties that can be readily tapped. Using light to excite these molecules, known as chromophores, he can create simple logic gates, or switches.
These nanostructures can then be used as the building blocks for a variety of applications, ranging from the biomedical to the computational.
"When light is shined on the chromophores, they absorb it, exciting the electrons," Dwyer said. "The energy released passes to a different type of chromophore nearby that absorbs the energy and then emits light of a different wavelength. That difference means this output light can be easily differentiated from the input light, using a detector."
Instead of conventional circuits using electrical current to rapidly switch between zeros or ones, or to yes and no, light can be used to stimulate similar responses from the DNA-based switches - and much faster.
"This is the first demonstration of such an active and rapid processing and sensing capacity at the molecular level," Dwyer said. The results of his experiments were published online in the journal Small. "Conventional technology has reached its physical limits. The ability to cheaply produce virtually unlimited supplies of these tiny circuits seems to me to be the next logical step."
DNA is a well-understood molecule made up of pairs of complimentary nucleotide bases that have an affinity for each other. Customized snippets of DNA can cheaply be synthesized by putting the pairs in any order. In their experiments, the researchers took advantage of DNA's natural ability to latch onto corresponding and specific areas of other DNA snippets.
Dwyer used a jigsaw puzzle analogy to describe the process of what happens when all the waffle ingredients are mixed together in a container.
"It's like taking pieces of a puzzle, throwing them in a box and as you shake the box, the pieces gradually find their neighbors to form the puzzle," he said. "What we did was to take billions of these puzzle pieces, throwing them together, to form billions of copies of the same puzzle."
In the current experiments, the waffle puzzle had 16 pieces, with the chromophores located atop the waffle's ridges. More complex circuits can be created by building structures composed of many of these small components, or by building larger waffles. The possibilities are limitless, Dwyer said.
In addition to their use in computing, Dwyer said that since these nanostructures are basically sensors, many biomedical applications are possible. Tiny nanostructures could be built that could respond to different proteins that are markers for disease in a single drop of blood.
Dwyer's research is supported by the National Science Foundation, the Air Force Research Laboratory, the Defense Advanced Research Projects Agency and the Army Research Office. Other members of the Duke team were Constantin Pistol, Vincent Mao, Viresh Thusu and Alvin Lebeck.
Source:
Richard Merritt
Duke University
HIV Protein Enlisted To Help Kill Cancer Cells
Cancer cells are sick, but they keep growing because they don't react to internal signals urging them to die. Now researchers at Washington University School of Medicine in St. Louis have found an efficient way to get a messenger into cancer cells that forces them to respond to death signals. And they did it using one of the most sinister pathogens around - HIV.
"HIV knows how to insert itself into many different types of cells," says senior author William G. Hawkins, M.D., assistant professor of surgery and a member of the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital. "A portion of the HIV protein called TAT can transport biologically active compounds into cells. TAT is small, but it can move massive molecules. You could almost hook TAT up to a train, and TAT would drag it inside a cell. So we've taken advantage of this ability."
In an article published online in the Annals of Surgical Oncology, the researchers describe using TAT to pull a protein called Bim into cancer cells. TAT alone cannot cause AIDS and has no adverse health effects. Bim acts as a tumor suppressor and causes cancer cells to die through apoptosis, a process by which cells "commit suicide."
The research team found that the TAT-Bim compound activated apoptosis mechanisms in cancer cells and augmented the cell-killing effect of radiation. When mice with malignant tumors were treated with TAT-Bim, their tumors shrank, and they survived longer than mice that didn't get the treatment. After 40 days, 80 percent of mice receiving TAT-Bim were alive compared to 20 percent of mice that didn't get the treatment.
Hawkins asserts that this success marks the beginning of a very promising new approach to cancer therapy. "This is the tip of the iceberg," he says. "Now that we've proven we can do this, we've started creating a battery of proteins that can push cancer cells to die."
Hawkins says he thinks treatments that activate apoptosis mechanisms could provide new options for patients with the deadliest cancers - such as pancreatic cancer - which have very low rates of survival. He says he believes that clinical trials of these compounds could be just a few years away.
Hawkins began researching TAT-Bim after discussions with co-author Richard S. Hotchkiss, M.D., professor of anesthesiology, medicine and surgery and associate professor of molecular biology and pharmacology. Hotchkiss was seeking proteins that inhibit apoptosis in patients with life-threatening infections and found that TAT-Bim had the unwanted effect of increasing cell death. Hawkins wondered if TAT-Bim could be effective against cancer, and a productive scientific collaboration began between their labs to exploit the anticancer potential of TAT-Bim.
"Unlike most healthy cells, cancer cells grow very fast. So they are always on the verge of running out of natural ingredients like sugars, and mistakes are accumulating in their DNA," Hawkins says. "This results in signals telling cancer cells to die, but the cells don't quite have the permission they need to do it. Proteins like TAT-Bim can tip the balance in favor of death."
To further enhance the cancer-killing power of TAT-Bim and similar proteins under development, Hawkins and his colleagues are working on a technique that will concentrate them within tumors while sparing healthy cells. In collaboration with Robert H. Mach, Ph.D. professor of radiology, they are linking the anticancer proteins to tracer molecules that selectively bind to cancer cells.
"Dr. Mach designed tracers to visualize cancer in PET (positron emission tomography) scans," Hawkins says. "By binding our molecules to the tracers, we can deliver them to cancer cells. We've seen phenomenal results in the lab."
Next Hawkins plans to combine pro-apoptotic proteins such as TAT-Bim with chemotherapy, radiation therapy and other anticancer therapeutics in hopes of further increasing cell-suicide signals within cancer cells.
Kashiwagi H, McDunn JE, Goedegebuure PS, Gaffney MC, Chang K, Trinkhaus K, Piwnica-Worms D, Hotchkiss RS, Hawkins WG. TAT-Bim induces extensive apoptosis in cancer cells. Annals of Surgical Oncology Jan 6, 2007 (advance online publication).
Funding from the Barnes-Jewish Hospital Foundation supported this research.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Siteman Cancer Center is the only NCI-designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine.
Contact: Gwen Ericson
Washington University School of Medicine
"HIV knows how to insert itself into many different types of cells," says senior author William G. Hawkins, M.D., assistant professor of surgery and a member of the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital. "A portion of the HIV protein called TAT can transport biologically active compounds into cells. TAT is small, but it can move massive molecules. You could almost hook TAT up to a train, and TAT would drag it inside a cell. So we've taken advantage of this ability."
In an article published online in the Annals of Surgical Oncology, the researchers describe using TAT to pull a protein called Bim into cancer cells. TAT alone cannot cause AIDS and has no adverse health effects. Bim acts as a tumor suppressor and causes cancer cells to die through apoptosis, a process by which cells "commit suicide."
The research team found that the TAT-Bim compound activated apoptosis mechanisms in cancer cells and augmented the cell-killing effect of radiation. When mice with malignant tumors were treated with TAT-Bim, their tumors shrank, and they survived longer than mice that didn't get the treatment. After 40 days, 80 percent of mice receiving TAT-Bim were alive compared to 20 percent of mice that didn't get the treatment.
Hawkins asserts that this success marks the beginning of a very promising new approach to cancer therapy. "This is the tip of the iceberg," he says. "Now that we've proven we can do this, we've started creating a battery of proteins that can push cancer cells to die."
Hawkins says he thinks treatments that activate apoptosis mechanisms could provide new options for patients with the deadliest cancers - such as pancreatic cancer - which have very low rates of survival. He says he believes that clinical trials of these compounds could be just a few years away.
Hawkins began researching TAT-Bim after discussions with co-author Richard S. Hotchkiss, M.D., professor of anesthesiology, medicine and surgery and associate professor of molecular biology and pharmacology. Hotchkiss was seeking proteins that inhibit apoptosis in patients with life-threatening infections and found that TAT-Bim had the unwanted effect of increasing cell death. Hawkins wondered if TAT-Bim could be effective against cancer, and a productive scientific collaboration began between their labs to exploit the anticancer potential of TAT-Bim.
"Unlike most healthy cells, cancer cells grow very fast. So they are always on the verge of running out of natural ingredients like sugars, and mistakes are accumulating in their DNA," Hawkins says. "This results in signals telling cancer cells to die, but the cells don't quite have the permission they need to do it. Proteins like TAT-Bim can tip the balance in favor of death."
To further enhance the cancer-killing power of TAT-Bim and similar proteins under development, Hawkins and his colleagues are working on a technique that will concentrate them within tumors while sparing healthy cells. In collaboration with Robert H. Mach, Ph.D. professor of radiology, they are linking the anticancer proteins to tracer molecules that selectively bind to cancer cells.
"Dr. Mach designed tracers to visualize cancer in PET (positron emission tomography) scans," Hawkins says. "By binding our molecules to the tracers, we can deliver them to cancer cells. We've seen phenomenal results in the lab."
Next Hawkins plans to combine pro-apoptotic proteins such as TAT-Bim with chemotherapy, radiation therapy and other anticancer therapeutics in hopes of further increasing cell-suicide signals within cancer cells.
Kashiwagi H, McDunn JE, Goedegebuure PS, Gaffney MC, Chang K, Trinkhaus K, Piwnica-Worms D, Hotchkiss RS, Hawkins WG. TAT-Bim induces extensive apoptosis in cancer cells. Annals of Surgical Oncology Jan 6, 2007 (advance online publication).
Funding from the Barnes-Jewish Hospital Foundation supported this research.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Siteman Cancer Center is the only NCI-designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine.
Contact: Gwen Ericson
Washington University School of Medicine
Scientists Find Potential Protein Biomarkers For Growth Hormone
Ohio University scientists have identified several proteins in mice that might act as biomarkers for growth hormone. The research could be the first step to finding a more reliable way to detect recombinant human growth hormone (rhGH), which some athletes and teenagers use illegally to boost muscle and reduce fat.
At the Endocrine Society annual meeting in San Francisco, scientists John Kopchick and Juan Ding presented a new study that pinpointed four proteins that significantly decreased or increased in the blood after exposure to bovine growth hormone, which is similar to human growth hormone.
The researchers injected six 6-month-old male mice with growth hormone for seven days. They studied blood samples from the mice and compared the results to six control animals. Kopchick and Ding scanned hundreds of plasma proteins and found four - apoA1, transthyretin, clusterin and albumin - that showed a strong reaction to growth hormone.
"They're in the blood, but we don't know if they're coming from liver, fat, muscle or the kidneys," said Kopchick, Goll-Ohio Professor of Molecular Biology with Ohio University's Edison Biotechnology Institute and College of Osteopathic Medicine.
Kopchick and Ding, a graduate student in biological sciences, are hopeful that the proteins could be viable biomarkers for growth hormone activity in humans as well.
"In mice we can control the variables and the environment, but humans are genetically diverse and have different lifestyles that impact growth hormone. So the results may point to future study in humans, but may not necessarily apply to humans yet," said Ding, who also is studying how to identify protein biomarkers for human aging.
Growth hormone is hard to detect because it has a serum half life of only 15 minutes. RhGH, an approved drug for individuals with growth hormone deficiency, also is identical to human growth hormone. The current method of detecting growth hormone, analyzing levels of insulin-like growth factor (IGF-1), isn't always accurate, the researchers said, as it is age and gender sensitive.
"If you have an 18-year-old Olympic athlete and a 38-year-old athlete, the IGF-1 values may look very different," said Kopchick, whose research is funded by the Ohio Eminent Scholars program and Ohio University's Edison Biotechnology Institute.
Because identification of rhGH misuse or abuse has high stakes - it can make or break an athletic career - the current method has too many variables to depend on, he said.
It's still early to tell whether these protein markers have the same age limitations, as the mice in the study live to only 2 years. But the markers may have longer half lives of several days, which would offer a wider testing window, he said.
Kopchick already is exploring how to detect rhGH in human blood and tissues through a project with Danish scientist J.O. Jorgensen. The team received a three-year grant from the World Anti-Doping Agency to look for protein markers in blood and tissues of human subjects exposed to rhGH or exercise, as well as patients with growth hormone disorders.
Source: Andrea Gibson
Ohio University
At the Endocrine Society annual meeting in San Francisco, scientists John Kopchick and Juan Ding presented a new study that pinpointed four proteins that significantly decreased or increased in the blood after exposure to bovine growth hormone, which is similar to human growth hormone.
The researchers injected six 6-month-old male mice with growth hormone for seven days. They studied blood samples from the mice and compared the results to six control animals. Kopchick and Ding scanned hundreds of plasma proteins and found four - apoA1, transthyretin, clusterin and albumin - that showed a strong reaction to growth hormone.
"They're in the blood, but we don't know if they're coming from liver, fat, muscle or the kidneys," said Kopchick, Goll-Ohio Professor of Molecular Biology with Ohio University's Edison Biotechnology Institute and College of Osteopathic Medicine.
Kopchick and Ding, a graduate student in biological sciences, are hopeful that the proteins could be viable biomarkers for growth hormone activity in humans as well.
"In mice we can control the variables and the environment, but humans are genetically diverse and have different lifestyles that impact growth hormone. So the results may point to future study in humans, but may not necessarily apply to humans yet," said Ding, who also is studying how to identify protein biomarkers for human aging.
Growth hormone is hard to detect because it has a serum half life of only 15 minutes. RhGH, an approved drug for individuals with growth hormone deficiency, also is identical to human growth hormone. The current method of detecting growth hormone, analyzing levels of insulin-like growth factor (IGF-1), isn't always accurate, the researchers said, as it is age and gender sensitive.
"If you have an 18-year-old Olympic athlete and a 38-year-old athlete, the IGF-1 values may look very different," said Kopchick, whose research is funded by the Ohio Eminent Scholars program and Ohio University's Edison Biotechnology Institute.
Because identification of rhGH misuse or abuse has high stakes - it can make or break an athletic career - the current method has too many variables to depend on, he said.
It's still early to tell whether these protein markers have the same age limitations, as the mice in the study live to only 2 years. But the markers may have longer half lives of several days, which would offer a wider testing window, he said.
Kopchick already is exploring how to detect rhGH in human blood and tissues through a project with Danish scientist J.O. Jorgensen. The team received a three-year grant from the World Anti-Doping Agency to look for protein markers in blood and tissues of human subjects exposed to rhGH or exercise, as well as patients with growth hormone disorders.
Source: Andrea Gibson
Ohio University
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