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PASADENA, Calif.-- Richard A. Andersen, the James G. Boswell Professor of Neuroscience at the California Institute of Technology, has been elected as a member of the Institute of Medicine (IOM). Andersen is one of 65 new individuals to be admitted to the elite organization, which was established in 1970 by the National Academy of Sciences and now has 1,538 active members. It is recognized as a national resource for independent, scientifically informed analysis and recommendations on human health issues. By their membership, inductees agree to volunteer their time on IOM committees examining health policy issues.
Andersen studies the neurobiological underpinnings of brain processes, including the senses of sight, hearing, balance, and touch, and the neural mechanisms of action and is a pioneer in the development of implanted neural prosthetic devices that would serve as an interface between severely paralyzed individuals' brain signals and their artificial limbs--allowing thoughts to control movement. Andersen says, "It's a very exciting time in neuroscience. After decades of study, our basic research is finally yielding findings we are able to translate into clinical advancements to help paralyzed people. Caltech has provided a unique environment for such study, as we in our lab have enjoyed close collaboration with bioengineers, electrical engineers, economists, and physicists as well as clinicians toward developing a neural prosthesis. The next step is to move our studies into clinical trials with human patients, an endeavor we will enter jointly with the medical community."
Andersen received his PhD from the University of California, San Francisco, in 1979, and was a postdoctoral fellow at Johns Hopkins Medical School. He was on the faculties of the Salk Institute and MIT before joining Caltech in 1993. He is a member of the National Academy of Sciences, and a fellow of the American Academy of Arts and Sciences and the American Association for the Advancement of Science. He is the recipient of a McKnight Foundation Scholars Award, a Sloan Foundation Fellowship, the Spencer Award from Columbia University, a McKnight Technical Innovation in Neuroscience Award, and a McKnight Neuroscience Brain Disorders Award. The new members of the IOM will be formally inducted during the annual meeting, which is scheduled for October 12-13, 2008.
PASADENA, Calif.- A team of California Institute of Technology researchers has found an unexpected link connecting schizophrenia and autism to the importance of covering your mouth whenever you sneeze.
It has been known for some time that schizophrenia is more common among people born in the winter and spring months, as well as in people born following influenza epidemics. Recent studies suggest that if a woman suffers even one respiratory infection during her second trimester, her offspring's risk of schizophrenia rises by three to seven times.
Since schizophrenia and autism have a strong (though elusive) genetic component, there is no absolute certainty that infection will cause the disorders in a given case, but it is believed that as many as 21 percent of known cases of schizophrenia may have been triggered in this way. The conclusion is that susceptibility to these disorders is increased by something that occurs to mother or fetus during a bout with the flu.
Now, researchers have isolated a protein that plays a pivotal role in that dire chain of events. A paper containing their results, "Maternal immune activation alters fetal brain development through interleukin-6," will be published in the Oct. 3 issue of the Journal of Neuroscience.
Surprisingly, the finger of blame does not point at the virus itself. Since influenza infection is generally restricted to the mother's respiratory tract, the team speculated that what acts as the mediator is not the mother's infection per se but something in her immune response to it.
To prove this, they triggered an artificial immune response in pregnant mice--giving them a faux case of the flu. The trigger they used was a snippet of double-stranded RNA called poly(I:C), which fools the immune system into thinking there has been an infection by an RNA virus.
A single, mid-gestation injection of poly(I:C) creates a strong immune response in a pregnant mouse. When her offspring reach adulthood, they display behavioral and tissue abnormalities similar to those seen in schizophrenia in humans.
Though there might be some disagreement over what it means for a mouse to be schizophrenic, these abnormalities are generally marked by inappropriateness of response and difficulty in coping. For instance, afflicted mice often show antisocial tendencies, have trouble internalizing basic cause-and-effect connections, and are anxious about entering wide-open spaces or interacting with novel objects. Moreover, some of these abnormal behaviors are corrected by antipsychotic drug treatment.
These behaviors then pose a new question, what in the mother's immune response caused the abnormalities?
At the cellular level, the innate immune response is driven by proteins called cytokines, which are produced by the body in response to infection. The researchers speculated that something was being transmitted to the fetus by one or more cytokines produced by the mother in response to her infection.
"It's known that humans that are treated--say, for cancer--with an experimental cytokine treatment can display very significant changes in behavior," says Paul H. Patterson, Biaggini Professor of Biological Sciences and senior author of the paper. "So we know cytokines can have dramatic effects, of the kind you see in schizophrenia."
The team tried injecting the pregnant mice with individual cytokines, rather than with poly(I:C). It turned out that after a single dose of a specific cytokine known as interleukin-6 (or IL-6), a mouse would give birth to offspring who, at maturity, exhibited the familiar schizophrenia- and autism-like behaviors.
To confirm the role of IL-6, Steve Smith, the lead researcher, gave fake colds (poly(I:C)) to two groups of pregnant, IL-6-free mice. One group had received anti-IL-6 antibodies which blocked IL-6; the other consisted of so-called IL-6 knockout mice (mice whose genetic makeup prevents them from synthesizing IL-6). In both groups, offspring grew up normal, showing that IL-6 is necessary for the maternal poly(I:C) treatment to alter fetal brain development and subsequent behavior in the offspring.
The decision to try injecting IL-6 was a long shot. "It is really unexpected that a single injection of a single cytokine would exert such a powerful effect," says Patterson.
The scientists are still unsure what it is about increasing IL-6 levels in the mother that causes undesirable effects in her offspring. "The most obvious possibility is that IL-6 acts directly on the fetal brain," the paper's authors say, but they acknowledge that the cytokine might also alter the transfer of materials across the placenta or might even alter the maternal immune system that gave rise to it, in effect triggering a low-grade rejection of the developing fetal tissue by the mother's body.
Once the exact role of IL-6 has been nailed down, there will still be more work to be done. The researchers are hunting for ways of preventing cytokines like IL-6 from inflicting their damage on the developing or maturing brain--perhaps via mechanisms involving other cytokines.
"We could certainly imagine that there would be anti-inflammatory cytokines that would be involved, that would be acting in the opposite direction," suggests Patterson. "We haven't tested those yet, but we would like to. We also want to test anti-inflammatory drugs in the postnatal offspring to see if we can normalize their behavior."
The paper's authors are Patterson and Stephen Smith, a graduate student in biology at Caltech; Jennifer Li, now a graduate student at the University of California Medical Center, San Francisco, who participated in the project as part of a Caltech Summer Undergraduate Research Fellowship; and Drs. Krassimira Garbett and Karoly Mirnics, both of the Department of Psychiatry and the Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University.
The research was supported by the National Institute of Mental Health and by the McKnight, Cure Autism Now, and Autism Speaks foundations.
PASADENA, Calif.--Two California Institute of Technology faculty members were named MacArthur Fellows today, each winning a five-year, $500,000 grant awarded to creative, original individuals that is often referred to as the "genius grant."
Michael Elowitz, Bren Scholar and assistant professor of biology and applied physics, and Paul W. Rothemund, a senior research fellow in computation and neural systems and computer science, are two of 24 MacArthur Fellows honored today. The accomplishments of both of this year's winners highlight the interdisciplinary nature of Caltech's research endeavors.
Michael Elowitz is a molecular biologist who combines mathematical and computational modeling with experiments on individual living cells to understand how genes and proteins interact to form circuits. These circuits allow the cells to interact with their environments, communicate with one another, and develop into multicellular organisms. He uses two different approaches; in the first, he tracks changes in proteins in natural genetic circuits with time-lapse movies, and in the second, he engineers new circuits that provoke alternative cellular behaviors. In one demonstration of new cell behavior, Elowitz created a simple synthetic genetic clock by programming cells to show oscillations in the level of a fluorescent protein as the cells grew.
More recently, Elowitz tackled the long-standing question of how cells reliably control their own behavior when the intracellular environment they depend on is so complex and unpredictable. He used fluorescence again; in this case, differences between how much of a red protein and how much of a green protein the cell made allowed him to see to what extent the expression of genes is intrinsically random. Currently, his lab investigates how cells make decisions about differentiating into different cell types.
"I was just dumbfounded, befuddled," Elowitz says about the phone call that told him he was a MacArthur Fellowship recipient. "It's amazing, it's very hard to believe. It just wasn't something I had thought about, and it was out of the blue." He stresses that his research is very collaborative, and says that "by far the greatest pleasure has been working with and learning from a spectacularly talented and fun group of scientists." He has no plans yet for the cash award.
After earning degrees from UC Berkeley and Princeton University, Elowitz joined the Caltech faculty in 2003.
Paul Rothemund's work, which he began over a decade ago, borrows tools from molecular biology to show that DNA can be used to perform the tasks of a computer.
Recently, he's used computers to design large DNA molecules that reliably self-assemble into microscopic shapes and patterns, like a map of the Americas or a pair of smiley faces 100 nanometers wide and two nanometers thick. He calls his technique "scaffolded DNA origami" because it involves folding a very long strand of DNA dozens of times, into different designs. Rothemund says this kind of DNA technology might eventually be used to build smaller, faster computers. He also envisions far more fantastical potentials, like building whole organisms from self-assembling biological bits.
Rothemund considers himself lucky to be working at a moment in history that has provided his detail-oriented personality with something to do. "I really like to make intricate things with lots of little parts. In a different age I'd probably be a watchmaker, although I am not that mechanically inclined." He has yet to decide what he'll do with the grant money, besides travel for future collaborations.
In keeping with the MacArthur tradition, the Caltech nominees did not know they were being considered. "It is amazing that such a thing exists," says Rothemund. "That one can pursue beautiful or meaningful or societally redeeming things with no interest in doing it for money, and then out of the blue, someone walks in and says 'Surprise, we're going to give you half a million dollars to keep doing whatever you think is beautiful or meaningful or important, and there are no strings attached and we aren't going to keep track of you or bother you again ever. . . bye!'"
After receiving degrees from the California Institute of Technology and from the University of Southern California, Rothemund returned to Caltech as a Beckman Fellow in 2001. He joins ranks with the director of his lab, Associate Professor of Computer Science and Computation and Neural Systems Erik Winfree, who was named a MacArthur Fellow in 2000.
PASADENA, Calif.--The stranglehold of nicotine addiction leads to more than four million smoking-related deaths each year. Scientists at the California Institute of Technology have now explained two roots of that addiction. The discoveries may offer new hope not just for smokers, but eventually also for sufferers of Parkinson's disease, a debilitating movement disorder that affects some 40 million people worldwide.
Researchers have known for decades that chronic exposure to nicotine increases the number of nicotine receptors--molecules that are activated by binding to the drug--on nerve cells. The binding of nicotine to these receptors, and in particular to one specific subunit known as alpha4, enhances the release of a pleasure-causing neurotransmitter called dopamine.
But "this increase is confusing," says Henry A. Lester, the Bren Professor of Biology at Caltech, "because for opioid addiction, and for many other classes of addictions and of drugs in general, the body attempts homeostasis and adjusts the number of receptors downward if there is a constant stimulus." Understanding this paradox--how it is possible that smokers become tolerant to the pleasurable effects of nicotine despite the fact that their brains produce new nicotine receptors in response to the chemical--is crucial for defeating nicotine's addictive power.
Lester, his postdoctoral researcher Raad Nashmi, and their colleagues at Caltech, the University of Colorado at Boulder, and the University of Pennsylvania School of Medicine, have now solved the mystery, by developing a special mouse strain with fluorescent nicotine receptors. These fluorescent tags allowed the scientists to monitor the effects of the nicotine throughout the brain, down to the level of individual neurons.
"We find that alpha4 containing receptors, those with some of the highest sensitivity to nicotine, are upregulated"--or increased in number--"by chronic nicotine in a cell-specific fashion," Lester explains. "In particular, the alpha4-containing receptors are indeed upregulated in the dopamine-producing portions of the brain, but not in the dopamine neurons themselves." Instead, the increase in receptor number occurs only in neurons that inhibit dopamine neurons--a group called the GABAergic neurons.
This surprising result led the researchers to conduct experiments with delicate electrical probes. In chronic nicotine-treated mice (and presumably in chronic smokers), the dopamine neurons are chronically inhibited from firing in the absence of nicotine. And nicotine itself still excites the dopamine neurons, leading to pleasure, but much less than expected.
"This research explains tolerance during nicotine addiction," Lester says. "Once in a while, an important piece of a puzzle does fall into place."
"This is outstanding work that will open the door to further studies of nicotinic receptor upregulation in the cognitive and rewarding effects of nicotine," comments Daniel S. McGehee of the University of Chicago, who studies the neurobiology of nicotine addiction. McGehee was not involved in the present research.
But there's more. In the special Caltech mice, the largest number of new nicotine receptors appeared in the mouse forebrain. This is the part of the brain involved in cognition. Electrical measurements showed that these new receptors also helped to boost synaptic transmission. The result may explain why many smokers claim that cigarettes actually help them think better--and why 44 percent of the cigarettes smoked in the United States are consumed by people with mental health problems.
"People may attempt to medicate themselves with nicotine, and my research is also aimed at trying to understand the mechanism behind that," Lester says.
"We now think that we need to concentrate on drugs that manipulate upregulation." Lester adds. His lab is currently developing simpler cell-based systems using the fluorescently labeled nicotine receptors. Using special microscopes, the effect of particular drugs on those receptors can be monitored.
One long-term benefit of the research could be the development of better therapies for Parkinson's disease, the chronic neurological condition that gradually destroys some dopamine cells. Although the cause of Parkinson's disease is unknown in most patients, one curious observation is that few smokers are ever affected. In fact, they seem to be protected against the condition. The reason, researchers suspect, is nicotine--and the new brain studies reveal that the reason may be those cell-specific differences in the regulation of nicotine receptors.
Previously, animal models of Parkinson's have shown that the excessive activity of dopamine neurons, firing in hysterical bursts, can lead to the death of those neurons. The affected neurons are located in a brain region called the substantia nigra, which is a center of voluntary movement control.
"These dopamine cells are actually persuaded by chronic nicotine to fire less, which may help them to live longer," says Lester, who hopes the research will lead to the development of drugs that act "very specifically" on these nicotine receptors and prevent cell death, "so people with the early stages of Parkinson's disease get the protection that they need."
The paper, "Chronic Nicotine Cell Specifically Upregulates Functional alpha4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path," was published in the August 1 issue of the Journal of Neuroscience. The research was supported by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression, and by previous grants from the California Tobacco-Related Disease Research Project, Philip Morris USA/International, the Elizabeth Ross Foundation, and the W. M. Keck and Plum Foundations.
PASADENA, Calif.- Applied physicists at the California Institute of Technology have figured out a way to detect single biological molecules with a microscopic optical device. The method has already proven effective for detecting the signaling proteins called cytokines that indicate the function of the immune system, and it could be used in numerous medical applications, such as the extremely early detection of cancer and other diseases, as well as in basic biological research.
According to Kerry Vahala, the Jenkins Professor of Information Science and Technology and professor of applied physics, this new detection technology revolves around a previous invention from his lab called an "ultra-high-Q microtoroid resonator." This is a donut-shaped glass device that is narrower than the width of a human hair and that is able to hold on to light very efficiently. Vahala explains that "the detector relies upon this feature to boost sensitivity to the single molecule level, albeit in a surprising way." He notes that the original idea was to detect an optical response elicited directly by molecules landing on the donut-shaped device. "As work proceeded, however, we were able to observe single molecule detection events with far greater ease than was originally expected." This pleasant surprise was traced to minute amounts of heat generated when molecules interact with the light stored within the microtoroid resonator. "This thermo-optic response boosts the sensitivity a millionfold," explains Vahala. Andrea Armani, who works in Vahala's laboratory and developed the detector as part of her thesis research, notes that besides being extremely sensitive, the device is also programmable by coating its surface with substances that react to a specific biological molecule. "The molecule which the device is targeting, whether it is a growth factor or a chemical like TNT, is determined by the surface treatment of the glass microtoroid. Fortunately, the biology and chemistry communities have developed very effective techniques for attaching proteins to glass surfaces, because most microscope slides are glass. All we had to do was adopt those techniques to fit our structure," explains Armani.
Vahala notes that "this combination of single-molecule sensitivity and programmable detection, that is, without labeling of the target molecule, has not been demonstrated before, and enables new kinds of tests and measurement."
Scott Fraser, the Rosen Professor of Biology, professor of bioengineering, and collaborator on the project, explains further that "this technology should lead to many applications for biological experiments, medical tests, and even medical treatments. The advantages are its ability to detect extremely small numbers of molecules, and the fact that there's no need to label target molecules. At this sensitivity level, it is possible even to study growth factors being emitted in real time from a single cell." Fraser adds, "This is the only sensor that currently has the requisite sensitivity and rapidity."
This type of experiment is important in monitoring how environmental changes, such as pH or temperature, can influence a cell's behavior. Currently, these types of experiments must be performed with populations of millions of cells, which often blurs results because it is like trying to pick out a single voice in a choir.
In the July 5 issue of the online journal Science Express, the team reports on its success in detecting a series of different molecules, including one immune response signaling protein, interleukin-2 (IL-2). For the latter, the targeting molecule the devices were coated with was a specific antibody that recognized IL-2. This surface preparation allowed the detector surface to bind the IL-2, while the thermo-optic mechanism provided the sensitivity required to detect the IL-2 at the single molecule level, even in serum (blood with the clotting factors and red blood cells removed).
"What is most exciting about this device is its ability to get single molecule results in real time without labeling. Because it can be programmed to detect almost any biological molecule, it is a universal detector, and as such opens the door to a whole field of new experiments," adds Armani.
The work was supported by the Defense Advanced Research Projects Agency-funded Center for Optofluidic Integration at Caltech.
The coauthors of the paper are Armani, a Clare Boothe Luce postdoctoral fellow; Vahala; Fraser; Richard Flagan, the McCollum-Corcoran Professor of Chemical Engineering and professor of environmental science and engineering; and Rajan Kulkarni, a recent Caltech biology doctoral graduate.
One way to stop malaria is to make the mosquitoes that carry the disease themselves resistant to the pathogen. Getting disease-fighting genes into the mosquito population can be tricky, however, because bugs carrying disease-resistance genes are likely to be less reproductively fit than their wild counterparts, and thus less likely to spread their genes naturally.
Associate Professor of Biology Bruce Hay of the California Institute of Technology, postdoctoral fellow Chun-Hong Chen, and their colleagues at Caltech and the University of California, Los Angeles, have come up with a novel method for introducing such genes into insect populations. The work, published recently in the journal Science, involves the creation of a selfish genetic element that is uniquely adapted to spread itself quickly throughout the population.
"This spread is essential," says Hay, "because people who live in areas affected by malaria and other mosquito-borne diseases are bitten often, so there will be little benefit unless most of the mosquito population is disease resistant."
"What we need," says Chen, the first author of the study, "is some way of forcing, or helping, these disease-resistance genes to spread rapidly throughout the wild population."
The technique Chen, Hay, and their colleagues have come up with uses a maternal-effect dominant embryonic arrest--or Medea--genetic element, a particularly spiteful selfish genetic element.
"Selfish genetic elements (single genes or clusters of genes) are basically units of genetic information that are more successful than your average gene at passing themselves from generation to generation," says Chen, even if their presence makes an organism less fit. "Our idea was to create a selfish genetic element that could be linked with a specific cargo, the disease-resistance gene, as a way of rapidly carrying this gene through the population."
Medea elements were first described in 1992 by Richard Beeman and colleagues at Kansas State University, who found the entity in populations of the common flour beetle Tribolium castaneum.
Beeman and his colleagues do not yet know the molecular nature of Tribolium Medea, but their work suggests that Medea consists of two linked genes. One gene, whose expression is activated in the mother, encodes a toxin that is deposited into all oocytes, or eggs. Embryos that do not inherit a Medea element die because of the toxin. Embryos that inherit Medea from either their mother's or their father's genome, however, will survive because they produce an antidote that neutralizes the toxin. As a result, chromosomes that carry Medea end up in offspring more often than those that do not, and Medea can spread rapidly through a population.
"We spent several years trying to create a selfish genetic element based on these principles," says Chen, "but it was difficult to get the insects to produce just the right amount of toxin; enough to kill the embryo, but not so much that the toxin couldn't be inhibited by the antidote." The researchers eventually switched to a system in which the toxin caused the loss of an essential function, and the antidote restored that function. "We generated flies in which maternal expression of small noncoding RNAs, known as microRNAs, were used to silence a gene known as myd88, which is crucial for embryonic development. Embryos from mothers expressing these microRNAs all died, unless they also expressed a microRNA-insensitive version of the myd88 gene: the antidote," said Chen.
Fruit flies carrying this synthetic Medea element spread quickly throughout a laboratory population of wild-type flies. After just a few generations, all of the flies in the population carried at least one copy of Medea. "To our knowledge this work represents the first de novo synthesis of a selfish genetic element able to drive itself into a population. It provides a simple proof-of-principle experiment demonstrating that, at least in a highly controlled laboratory environment, in a model organism, we can change the genetic makeup of a population," says Hay.
The team now plans to use the technique to transmit a real payload--a disease-resistance gene--into the mosquito.
Says Hay: "Mosquitoes with a decreased capacity to transmit malaria and other mosquito-borne diseases have already been identified in the wild and created in the laboratory by other researchers. These observations tell us that we can manipulate the mosquito immune system and thereby, at least in principal, stop this and other mosquito-borne diseases at their source in the mosquito. When combined with a mechanism such as Medea that helps to spread these resistance genes through the wild population, there is a real possibility that disease transmission can be suppressed in an environmentally friendly way that does not involve the wholesale use of insecticides or modification of the environment; the mosquitoes will still be there but with one or two tiny genetic changes that make them unable to transmit these dreadful diseases."
"This work is a prime example of how fundamental research can lead to breakthroughs that have huge implications for bettering human health," says Marion Zatz, chief of the Developmental and Cellular Processes Branch at the National Institute of General Medical Sciences, which partially supported the research. "Dr. Hay's work on how microRNAs regulate cell death in the innocuous fruit fly has 'borne fruit' in potential applications for limiting the spread of malaria."
This work was supported by National Institutes of Health grants GM057422 and GM70956 to Bruce Hay, and NS042580 and NS048396 to Ming Guo, assistant professor in the departments of neurology and pharmacology at UCLA's Brain Research Institute, David Geffen School of Medicine.
Contact: Kathy Svitil (626) 395-8022 email@example.com
Visit the Caltech Media Relations Web site at: http://pr.caltech.edu/media.
PASADENA, Calif.—In a development that could potentially benefit victims of degenerative neurological diseases, researchers have succeeded in stimulating the growth of adult neural stem cells. Such cells could then be directed towards repairing one's own brain.
In the November 15 issue of the Journal of Neuroscience, California Institute of Technology neuroscientists report that they have discovered a way to stimulate an area of the brain where adult stem cells normally exist. As a result, there is a significant increase in stem cell production—up to six times the normal amount of adult neural stem cells found there.
According to Paul Patterson, the Biaggini Professor of Biological Sciences at Caltech and senior author of the paper, the good news is that these stem cells represent a large pool of precursor cells that future work may direct into pathways for replacement of dying cells in disorders such as Parkinson's and Alzhiemer's diseases and multiple sclerosis.
"Basically, what my colleague Sylvian Bauer has done is take a natural protein in the body called leukemia inhibitory factor, or LIF, and inject it into the brains of adult mice," Patterson explains. "The results show that you can stimulate the subventricular zone to produce a much larger pool of adult neural stem cells."
The idea then is to direct the stem cells to form the necessary specialized neurons or glia in the part of the brain that is damaged by disease or injury, Patterson says.
"Neuroscientists have known for some time that the adult brain possesses neural stem cells that could be used to regenerate neurons, and in fact, the brains of neurodegenerative disease patients show evidence that their neural stem cells do attempt to replace dying cells.
"However, the contribution of these cells to brain repair is currently very limited," he says. "Our approach may overcome the limitation of cell numbers, and the approach of using one's own cells offers the further advantage of avoiding the transplantation of immunologically foreign stem cells, thereby eliminating the problems of rejection."
This development in no way renders the use of embryonic stem cells obsolete, or argues against further research with embryonic stem cells, Patterson says. Embryonic stem cells have the potential to become any cell in the body, whereas his process uses adult neural stem cells for brain disorders only.
Although this stimulation of neural stem cell growth has been done in laboratory mice, Patterson says that humans also have neural stem cells in the adult brain.
The next step is to see if the adult neural stem cells can be directed to replace cells in mice with brains that are damaged in ways similar to humans with Parkinson's, Alzheimer's, and multiple sclerosis.
Bauer, the lead author of the paper, is a former postdoctoral researcher in Patterson's lab who recently moved to the Université Paul Cézanne, Aix-Marseille III, in France.
PASADENA, Calif.—A group of 240 researchers from more than 70 institutions has announced the sequencing of the male California purple sea urchin. An animal frequently used in experiments, its genome has been studied intensely for years at Caltech's Kerckhoff Marine Biological Laboratory (KML), and will contribute significantly to biomedical advances of the future.
Reporting in the November 10 issue of the journal Science, the researchers are announcing that the high-quality "draft" sequence covers more than 90 percent of the sea-urchin genome. In addition to the primary results in Science, 41 companion manuscripts will appear in Science and a special issue of the December 1 issue of Developmental Biology.
The project was led by Erica Sodergren and George Weinstock, a husband-and-wife team at the Baylor College of Medicine-Human Genome Sequencing Center (BCM-HGSC), along with Richard Gibbs, director of the BCM-HGSC, and Eric Davidson and Andrew Cameron of the California Institute of Technology. The National Human Genome Research Institute of the National Institutes of Health provided most of the funding for the sequencing and annotation.
According to the researchers, the sea-urchin genome contains more than 814 million letters, spelling out 23,300 genes. To date, nearly 10,000 of the genes have been scrutinized by the international consortium.
The results are the outcome of work begun at Caltech more than 30 years ago, when Davidson and Roy Britten, a scientist working at Caltech's Kerckhoff Marine Biological Laboratory, began to exploit the utility of the sea urchin as an experimental animal and decided to develop it as a model system in the then emerging field of molecular biology. In the ensuing years many advances in cell and developmental biology derived from this decision.
"Roy Britten and Eric Davidson offered a comprehensive theory of gene regulation in higher organisms, and the sea urchin has been the premier model for testing these predictions," says Gibbs. "The complete sequence is now available to further these studies."
More recently, Davidson and Cameron have coordinated efforts to have the sea-urchin genome sequenced. Starting with a special grant from the Stowers Institute for Medical Research in Kansas City, they assembled the research materials that would be needed to sequence the genome at the Sea Urchin Genome Facility in Caltech's Beckman Institute and at the KML.
A culture system at KML in which the purple sea urchin is grown through the life cycle continues to provide the essential infrastructure. When the Human Genome Research Institute announced a way to propose additional genome sequencing to support the human genome information, the team at the BCM-HGSC was poised to take action. From these roots grew the Sea Urchin Genome Sequencing Consortium.
Sea urchins are echinoderms (Greek for spiny skin), marine animals that originated over 540 million years ago and that include starfish, brittle stars, sea lilies, and sea cucumbers. Following the great extinction of animals 250 million years ago, the modern sea urchins emerged as the dominant echinoderm species. The purple sea urchin emerged in the North Pacific Ocean during a rapid burst of speciation and diversification 15-20 million years ago.
There was great interest in the sea urchin as a target for genome sequencing because these animals share a common ancestor with humans. That ancestor lived over 540 million years ago and gave rise to the Deuterostomes, the superphylum of animals that includes phyla such as echinoderms and chordates, the phylum to which humans and other vertebrates belong. All Deuterostomes are more closely related to each other than they are to any other animals not included in the Deuterostome superphylum. For example, among sequenced genomes, the genomes of fruit flies and worms are more distant from the sea urchin genome than is the human genome. "Each genome that we sequence brings new surprises. This analysis shows that sea urchins share substantially more genes and biological pathways with humans than previously suspected," says Francis S. Collins, director of the National Human Genome Research Institute. "Comparing the genome of the sea urchin with that of the human and other model organisms will provide scientists with novel insights into the structure and function of our own genome, deepening our understanding of the human body in health and disease." To discover how sea urchins and humans can be so different, yet be related by descent from an ancient relative, their genomes were compared. The sea urchin is an invertebrate and the first example of sequencing a Deuterostome genome outside the chordates. Most previous invertebrate genomes that were sequenced, such as insects and nematodes, were animals outside the Deuterostome superphylum, although one genome of a chordate invertebrate, the sea squirt, has been sequenced. The sea urchin lies evolutionarily in a large niche between the chordate branch of the Deuterostomes and the non-Deuterostome superphyla. "The sea urchin fills a large evolutionary gap in sequenced genomes," says Weinstock, co-director of Baylor's Human Genome Sequencing Center. "It allows us to see what went on in evolution after the split between the ancestors that gave rise to humans and insects. The sea urchin genome provided plenty of unexpected rewards and was a great choice for sequencing." The comparison of the genes of the sea urchin to the human gene list shows which human genes are likely to be recent innovations in human evolution and which are ancient. It also shows which human genes have changed slowly in the lineage from the ancestral Deuterostome animal and which genes are evolving rapidly in response to natural selection. This will make it possible one day to know the history of every human gene-and build a picture of what the extinct ancestors that gave rise to animal life ranging from worms to humans looked like. Although invertebrate sea urchins have a radically different morphology from humans and other vertebrates, their embryonic development displays basic similarities, an important shared property of Deuterostome animals. This distinguishes them from Protostomes, which have a different pattern of embryonic development. This makes the sea urchin, with its many useful properties such as transparent embryos and ease of isolation of eggs and sperm, a valuable model for studying the process of development and helping us to understand human development. The development of the animal occurs through a complex network of genes, making the sea urchin one of the main models for systems biology, which describes how the building blocks of an animal interact in time and space. Sea urchins provide a rapid and efficient gene transfer system. By injecting DNA into the egg, researchers can determine which letters spell instructions for turning genes on and off. The series of genetic switches leading to the ordered cascade of expression of genes after fertilization in the sea urchin is among the best understood developmental systems among animal models. Now, with the genome sequence in hand, a more complete set of components of development are known, and this process can be studied exhaustively.
Because of its evolutionary position, the sea-urchin genome sequence was a sample of unknown biological territory. Some of the notable surprises and discoveries were that: —The sea urchin has most of the same gene families found in human beings. These gene families make up the Deuterostome tool kit used to create animals in this superphylum. However, the size of gene families is often larger in humans, reflecting, in part, two whole genome duplication events during vertebrate evolution after the separation of the sea urchin and human evolutionary lines. —One unexpected exception to this size rule is the immune system. Humans have innate and acquired immune systems. The sea urchin has some of the genes of the acquired immune system, but its innate immune branch is greatly expanded with ten- to twenty times as many genes as in humans. —Innate immunity is the set of proteins that are "hard wired" to detect unique molecules within bacteria, such as their cell walls, and to signal that there is an intruder. This rich repertoire of sea urchin proteins could turn out to provide new reagents in the fight against infectious diseases. —The sea urchin has genes for sensory proteins that are involved in human vision and hearing. Yet the sea urchin has no eyes and ears, at least as we know them. Some of the visual sensory proteins are localized within an appendage known as the tube foot, and likely function in sensory processes there. It is remarkable that the same sensory proteins are used in organs with such different structures in sea urchins and humans. "The sea urchin reminds us of the underlying unity of all life on earth," notes Sodergren. "It is a similar set of genes and proteins being reused in different ways, different numbers, and at different times in the life cycle to create the diversity of living forms." The sea-urchin genome was one of the most challenging to sequence to date at Baylor. The genome is highly polymorphic, meaning that the two copies of the genome in the diploid organism vary from each other by about 4 percent, or one difference in spelling every 25 letters. This posed a formidable challenge in assembling the nine million separate short sequences produced by DNA sequencing. A new approach was used, emphasizing the use of BAC clones as a framework. Each BAC clone represents only one version of the genome spelling, and thus provides a consistent sequence on which to build the genome. To sequence the 8,000 BAC clones covering the genome, another new technique was used. The process, CAPSS (clone-array pooled shotgun sequencing), sequences mixtures of BAC clones, rather than individual ones, and then assigns portions of the mixture of sequences to the proper clone. This reduces the cost and time to do the genome by an order of magnitude. The sea-urchin project was thus a test bed for innovations in whole genome sequencing. The sea-urchin project is one of more than 20 projects involving animal genomes that Baylor's Human Genome Sequencing Center has undertaken, including the human genome and those of primates like the rhesus monkey, other mammals like the cow and wallaby, insects such as the honey bee, beetle, and wasp, and most recently the dolphin. In addition, numerous microbes have been sequenced, with a focus on infectious diseases. Other projects include studying the genetic basis of human disease, and this will be the major emphasis of future work.
PASADENA, Calif.—A new $4.4-million grant from the National Science Foundation will allow researchers at the California Institute of Technology and the University of California, Berkeley, to develop techniques to turn brain cells on and off in animals as they go about their daily activities, allowing the scientists to understand the details of how brain activity leads to complex behaviors.
According to principal investigator Michael Dickinson, the Zarem Professor of Bioengineering at Caltech, the five-year program is aimed at solving one of the remaining great challenges facing biologists—understanding the mechanistic basis of complex behavior. The work will focus on fruit flies, which are a powerful model system understood extremely well at the genetic level.
"New approaches available in molecular genetics can now be applied to manipulate individual brain cells in an attempt to understand how brains control behavior," says Dickinson. "We'll also use recent advances in engineering to create new devices to observe and measure behavioral changes in a manner as rigorous as those available to detect genetic differences."
The work will involve experiments in which the activity of specific cells in the nervous systems of fruit flies can be controlled using light. "The idea is to bioengineer ion channels that can be opened and closed with light flashes," Dickinson explains. "By controlling these genetically engineered ion channels, we can directly manipulate the electrical impulses that nervous systems use to sense and process information.
"This approach will allow us to study the function of specific cells and circuits in intact animals," Dickinson adds. Coinvestigator Ehud Isacoff of the University of California, Berkeley, will create these ion channels.
A fly might be engineered, for example, to begin flying or walking when pulsed with light of a certain wavelength. But this would be a means to a scientific goal and not the ultimate goal itself.
"This is one way of tapping into the fly and making cells do what we want them to do in order to test specific hypotheses about brain structure and behavior," Dickinson says. David Anderson, a coprincipal investigator and the Sperry Professor of Biology at Caltech, will work to place the light-controlled ion channels within as many unique cells in the flies' nervous systems as possible.
Prior work on the cellular basis of behavior has focused on how networks of brain cells may control simple behaviors such as swimming, flying, and feeding. The new work will probe these behaviors at a deeper level, attempting to figure out how nervous systems-and possibly even individual nervous-system cells-regulate simpler motor actions over time and space to generate more complex behaviors.
A central goal of the research will be to determine how a nervous system uses sensory data to process changes in a complex set of behaviors. Thus, the scientists will not only study the details of how the flies' sensory-based locomotion (walking and flying) works, but how their locomotion is related to crucial survival activities such as looking for food, seeking mates, laying eggs, searching for shelter, and getting out of harm's way.
"We will begin with the assumption that an animal's own natural behavior is the best context in which to interpret how its nervous system is built," Dickinson says. "The first step is to gather quantitative behavioral information concerning the external and internal cues that cause flies to change or modulate what they are doing.
"The next step is to gain experimental access to the specific cells that control these behavioral transitions, so we will develop genetically engineered flies that allow us to control the neurons that send information from the sensory areas of the brain to the circuits that generate and control movement. We will also study how gene expression controls and alters brain wiring.
"Collectively, this may help unravel one of the central questions in neuroscience: how brains regulate behavioral transitions."
Additional information on this and related grants is at http://www.nsf.gov/news/news_summ.jsp?cntn_id=108068&org=NSF&from=news
PASADENA, Calif.—The National Human Genome Research Institute (NHGRI), a component of the National Institutes of Health (NIH), has awarded an $18-million grant for creation of a Center of Excellence in Genomic Science at the California Institute of Technology.
According to Marianne Bronner-Fraser, the Ruddock Professor of Biology at Caltech and principal investigator of the five-year program, the goal will be to image and mutate every developmentally important gene in vertebrates—that is, animals with backbones.
The work will be performed together with co-investigators Sean Megason and Scott Fraser from the Division of Biology, and Niles Pierce, an assistant professor of applied and computational mathematics and bioengineering.
"We will combine real-time analysis of gene expression on a genome-wide scale with the ability to mutate genes of interest," Bronner-Fraser says.
Initially, the research team will focus on the zebrafish, which is ideal for this type of work because of its transparent embryo and its rapid development.
"Our goal is to create the 'digital fish,'" Megason says. "This will be a computer model of the genetic orchestra that transforms an egg into an embryo."
"There will be an enormous payoff in new information about how development works at the genomic level," Bronner-Fraser adds.
The researchers will use new "in toto" imaging and genetic tagging tools invented by Megason and Fraser and new molecular detection methods being developed in the Pierce lab to analyze gene expression and function in the developing embryos. They will digitize this molecular data on a genomic scale by capturing thousands of time-lapse videos as the animals develop.
Once the approach is worked out on zebrafish, it will also be applied to the Japanese quail to make a "digital bird," because bird embryos develop in a fashion very similar to human embryos.
The Caltech grant is part of a $54-million grant portfolio awarded by the NHGRI for funding interdisciplinary work in genomic research. The NHGRI is best known for spearheading the Human Genome Project, which completely mapped the genetic blueprint of humans.
Now that the sequence of the genome for humans and many other species has been determined, the challenge ahead is to figure out how the genome functions during development and disease which is the goal of the CEGS (Center for Excellence in Genomic Science) program.
"The CEGS program is vital to our efforts to apply innovative genomic tools and technologies to the study of human biology," said NHGRI Director Francis S. Collins. "By fostering collaboration among researchers from many different disciplines, NHGRI aims to encourage innovation and build a powerful new framework for exploring human health and disease."


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Enjoy Florida's Gold Coast as you cruise down Fort Lauderdale's beautiful waterways on this exciting Venice of America tour!
The modern, elegant yacht which you will be traveling aboard offers the utmost in comfort with a new and completely redesigned interior, panoramic views and air-conditioned salons. As you enjoy the scenery you may purchase light snacks and additional drinks from the bar. Some of the finest captains in the South Florida area (all Coast Guard licensed) will narrate the fascinating sights, history and legends of the waterways.
Breathtaking views will be yours to see along the New River, the Intracoastal Waterway and Port Everglades. This truly luxurious cruise will give you a real taste of how the rich and famous live, making your adventure a memorable one-of-a-kind vacation experience for you, your family and friends. There's nothing like it, not even in Venice!
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Data that KRAS is a clinically relevant biomarker for Vectibix is confined to the monotherapy setting; there is not yet sufficient data with Vectibix in combination with chemotherapy to conclude that KRAS is a valid predictive biomarker in that setting. However, pivotal studies "181" and "PRIME ("203") will be the first prospective Phase 3 clinical studies to test the effect of Vectibix in wild-type KRAS tumors in combination with chemotherapy and to determine the clinical utility of KRAS as a predictive biomarker in mCRC. Data from these trials will be available in 2009.
"Based on available data, we believe that focusing Vectibix treatment on patients with wild-type KRAS tumors will avoid unnecessary adverse events in patients who are unlikely to benefit, maximize response rates and PFS in patients with wild-type KRAS genes, and redirect patients with a mutated KRAS gene to alternative therapies," said Sean Harper. "We are thrilled to be taking a step forward in advancing the field of personalized medicine by being one of the first to realize the clinical potential of the KRAS gene in guiding treatment of advanced colorectal cancer patients."
In November, the National Comprehensive Cancer Network (NCCN) announced updates to their Guidelines on Colon and Rectal Cancers that included the recommendation that a determination of the KRAS gene status of either the primary tumor or a site of metastasis should be part of the pre-treatment work-up for patients diagnosed with metastatic colorectal cancer. Further, the guidelines recommended that EGFr inhibitors, including Vectibix, should only be used in patients with tumors characterized by the wild-type KRAS gene.
|SOURCE Amgen
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HTTP Servers Software
The Centaurus-Platform extends the Tomcat 5.x-Server. There is a integrated Module-Installer to install additional Modules to make the Tomcat more usefull. All installation will be done with Apache Ant.8 weekly downloads
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%% Image selected per Image Pickin' thread: http://tvtropes.org/pmwiki/posts.php?discussion=1361997010031682800
%% Please do not replace or remove without starting a new thread.
[[quoteright:300:[[Myth/SaintGeorge http://static.tvtropes.org/pmwiki/pub/images/Saint_George_Killing_the_Dragon_6828.jpg]]]]
[-[[caption-width-right:300:''St. George Killing the Dragon'' by Bernat Martorell]]-]
->''"I don't know about you guys, but... I kinda want to slay the dragon."''
-->-- '''Series/{{Angel}}''' , ''[[GrandFinale Not Fade Away]]''
A dragon is usually a job for an entire party of adventurers. So how can The Dragonslayer do this themselves? Well, having the [[{{BFS}} Greatsword]] [[WeaponOfXSlaying of Dragonbane]] [[InfinityPlusOneSword +1]] and the strength to lift and wield it helps. But beyond incredible strength and skill, they must have knowledge. They must know various weaknesses of dragons, such as that the scales near the belly are especially thin, the space between eyes (or heck the eyes themselves), or the nape of the neck are vital points. They also have to know specific weaknesses of elemental and chromatic dragons, such as that an ice dragon cannot abide large amounts of salt.
[[Administrivia/TheSameButMoreSpecific So this is just a variant]] of TheHunter right? Well, no. TheHunter normally suffers the AchillesHeel of CripplingOverspecialization, while The Dragonslayer still has a giant sword, which unlike a stake or silver daggers, [[OneHeroHoldTheWeaksauce is very effective in battle]]. The Dragonslayer is often TheHero with a few dead dragons tacked on.
But that's assuming the truth. Dragon slayers have a reputation for being MilesGloriosus, to the point where even the real deal is viewed with skepticism. Perhaps the one rumored to be a dragon slayer isn't, and you instead need to look for his brother, or maybe [[DistaffCounterpart sister]]. Or maybe their great-grandfather was one, but nobody in the family knows how to do it anymore.
It is important to note that having killed ''one'' dragon does not necessarily make one a dragonslayer, just as having saved one person makes them a hero but not TheHero. This is basically part of their job description, meaning they generally hunt dragons, plural. The other qualification, of course, is surviving the encounter. Not the person who gets rid of TheDragon, unless we're being literal here.
[[folder: Anime and Manga]]
* ''Franchise/DragonAge: Anime/DawnOfTheSeeker'' reveals that the family of ''VideoGame/DragonAgeII'' character Cassandra Pentaghast has quite a reputation as dragonslayers. In the course of the film, Cassandra takes out a grand total of ''six'', five of them in the same scene.
* ''Manga/FairyTail'' has the Dragon Slayer magic (''metsuryuu mahou'', [[note]]literally "dragon-''destroying'' magic"[[/note]]), a special type of elemental magic taught to certain humans by Dragons, which is said to be really effective against other Dragons. It also slowly transform the user to a dragon. [[spoiler: Canonically, Acnologia was once a ''really'' bloodthirsty Dragon Slayer who massacred tons of dragons, until he was eventually turned into a giant dragon himself.]] It's not so much that Dragon Slayer magic is especially effective against Dragons; rather, it's pretty much the ''only'' thing that can even scratch them. Even then, the Dragon Slayer has to be really powerful to stand a chance against a real Dragon. Seems to be a case of like working against like: one of the only things that can really hurt a Dragon is another Dragon. Dragon Slayers are simply humans using Dragon magic.
* In ''Manga/OnePieceWanted'', set in the same continuity as ''Manga/OnePiece'', the legendary swordmaster and samurai Ryuuma's greatest and best known feat was killing a huge dragon in a single hit. [[spoiler: During the Punk Hazard arc, Zoro mirrors Ryuuma by beheading a large dragon in a similar manner.]]
* Parn from ''Roleplay/RecordOfLodossWar'' has over the course of the show killed at least two dragons, one in the first episode, and the other was an ancient dragon.
* Lina Inverse from ''LightNovel/{{Slayers}}'' does not qualify, even though she's killed hundreds of dragons, because her technique is seen as overkill and not involving real skill. She does however meet an actual dragon hunter, on her quest for gourmet cuisine (he's less a {{BFS}} variety, and more a specialist that uses knife skills).
* ''Anime/TheVisionOfEscaflowne'' starts off with Van fighting a dragon in a specialized dragon-fighting suit of armor. There's a folding pop-out shield that he can extend to protect him from flame breath, there's a crossbow on one arm, and if needs be he can shed the whole thing at once for added mobility. Dragonslaying is apparently a very important thing in his world, since it's how you get energist crystals for powering giant robots. It's also his rite of passage as the king of his small country.
* [[MeaningfulName Georgia]] of ''Anime/{{Pokemon}}'' is a self-proclaimed "Dragon Buster", a trainer dedicated to taking down dragon-[[ElementalRockPaperScissors type]] Pokemon. To this end, her team is mostly made up of ice-types, which were at the time the dragon-type's only weakness aside from itself.
* In the manga ''Rain'', the main character Rain gained the title of "dragon slayer" after he supposedly single-handedly fought and killed a dragon in one-on-one combat and absorbed the dragon's lifeforce and power.
[[folder:Comic Books]]
* In ''ComicBook/{{Smax}}'' (the spin-off from ''ComicBook/TopTen''), Smax is revealed to have started out as a professional dragonslayer before moving across worlds to become a policeman in Neopolis.
* Marvel comics' ''Comicbook/TheMightyThor'' related books have Sigurd (the Ever-Glorious) also mentioned under mythology and, despite all the flaws this incarnation of the guy has (like being huge JerkAss), he killed a dragon and got even more immortal thanks to it.
[[folder: Film]]
* The protagonist in ''Film/{{Dragonheart}}'' is a professional dragonslayer, [[spoiler:seeking to kill the last dragon whose heart is making the king an immortal tyrant. He gives up the grudge after befriending said dragon and realizing that the heart only made the king immortal -- the king was always evil. In the end, he has no choice but to act as a dragonslayer one last time to put an end to the villain once and for all.]]
** The villain's mother, the Queen Dowager, also hires dragonslayers to kill the last dragon[[spoiler:, so her son will die with him]]
* In ''Film/ReignOfFire'', Van Zan (and his fellow Americans) are all specialists in slaying dragons. They have knowledge of the dragons' weaknesses and exploit these with a range of specialized equipment, including a tank and a helicopter which can drop troops onto flying dragons to force them to land.
%%* The aptly named Film/{{Dragonslayer}}. %% Zero context example. Please provide context.
[[folder: Literature]]
* Fred Saberhagen's ''The First BookOfSwords''. Nestor was already in the dragon-hunting trade when the god Hermes gave him Dragonslicer. With that Sword he found he could kill dragons easily.
* Cadderly from ''TheClericQuintet'' qualifies, even though he's a spellcaster. He managed to kill one with a explosive bandolier, and he [[CrowningMomentOfAwesome managed to brainwash another into doing his bidding]].
* The main characters of the ''TabletopGame/ForgottenRealms'' novel trilogy ''Literature/TheYearOfRogueDragons'' are an adventuring party who specialize in taking down dragons, slaying several evil dragons per book. ItsPersonal for the leader, [[ArtificialLimbs half-golem]] Dorn Graybrook, who lost his family and two limbs to a dragon attack as a child. Over the course of the trilogy, though, he not only allies with several good-aligned dragons, but even falls in love with a female song dragon.
* In ''Literature/TheHeroAndTheCrown'', Lady Aerin becomes a dragonslayer after working out a reasonably safe method for doing so. Her ownership of a powerful magical sword helps, of course.
* ''Literature/{{Dragonsbane}}'' by Creator/BarbaraHambly has a prince go in search of a dragonslayer who the legends describe as a KnightInShiningArmor who killed the dragon with his sword. He turns out to be [[ExpectingSomeoneTaller a rather bookish man]] who [[CombatPragmatist disabled the dragon with poisoned harpoons]] and finished it with a battleaxe.
* Creator/TomHolt's ''Paint Your Dragon'' plays with the trope. Myth/SaintGeorge is an out-and-out treacherous bastard, and the dragon is closer to being a hero. The dragon just wants a fair fight.
* In Creator/JohnMoore's ''Slay and Rescue'', Prince Charming is quite the dab hand at rescuing princesses from dragons, and has developed several specialized techniques for dragonslaying. He just wishes the princesses would be a little more demonstrative in their thanks.
* {{Deconstructed}} in ''Literature/SwordOfDestiny'', where dragon slayers are depicted either as [[WindmillCrusader idealistic buffoons out of touch with reality]] or [[ProfessionalKiller thuggish, ruthless (but efficient) poachers]].
* Invoked in the final book of ''Literature/TheWheelOfTime'', when [[HeroKiller Demandred]] proclaims himself to be the dragonslayer and a DarkMessiah. However, in his case the dragon he's come to slay is the local ChosenOne, who goes by that title, not a scaly fire-breathing best.
* Deconstructed in ''[[Literature/MediochreQSethSeries The Good, the Bad and the Mediochre]]''. Maelstrom is a dragon slayer - described as such in-universe, in fact - but since the setting is one where dragons are rarely evil and often sapient, this just makes him a massive, [[FantasticRacism speciesist]], douchebag PsychoForHire.
%%* [[IronWoobie Túrin Turambar]] and Eärendil in ''Literature/TheSilmarillion'' %% Zero context example. Please provide context.
%%* Bard in ''Literature/TheHobbit'' %% Zero context example. Please provide context.
* Music/BobMarley is depicted as a dragon slaying knight on the cover of his posthumous album ''Music/{{Confrontation}}'' (1983).
[[folder: Mythology]]
* Myth/SaintGeorge (c. 275-303 AD) is famous for slaying a dragon since the 11th century (there was no mention of George's dragon-fight prior to that). The real George was a Syrian-born Roman legionnaire who was executed for refusing to sacrifice to the Roman gods. The legend is possibly inspired by Eastern icons of George fighting a dragon in which the dragon was (in reference to the dragon of Literature/{{Revelation}}) merely a symbol of Rome and/or paganism, but eventually the scene came to be understood literal.
* Aided by his one faithful retainer Wiglaf, Literature/{{Beowulf}} battled and killed a dragon that had devastated his kingdom of Geatland, but died of his wounds afterwards.
* Myth/ClassicalMythology: Bellerophon was famous for killing the Chimera, a fire-breathing monster that was part lion, part goat, and part snake.
* In Myth/NorseMythology, the hero Sigurd a.k.a. Siegfried was chiefly famous for killing a huge dragon somewhere near the Rhine.
* In ''Pinball/MedievalMadness'', the player must slay a dragon in order to rescue one of the princess by shooting the damsel ramp.
* Sir Tristan has this task in ''VideoGame/GoldenLogres''
* The player must do this as one of his duties in the "Dragon's Keep" table of ''VideoGame/FullTiltPinball''
[[folder:Professional Wrestling]]
* El Cazador De Dragones Eragon in IWRG and Wrestling/{{N|ationalWrestlingAlliance}}WA Mexico.[[/folder]]
[[folder:Tabletop Games]]
* ''TabletopGame/DungeonsAndDragons''
** The ''Council of Wyrms'' campaign setting introduced the Dragon Slayer kit. Dragon Slayers are human beings specially trained to kill dragons. They are immune to dragon-caused fear, gain bonuses when attacking dragons, and have armor and weapons that are more effective against dragons. They are dedicated to the goal of eradicating dragonkind.
** Then there are rangers who choose Dragon as their favoured enemies. Of course, said rangers are encouraged to be very, ''very'' careful when working.
* ''TabletopGame/{{Shadowrun}}''. There is an organization of dragon hunters that killed many dragons during the down cycle while they hibernated, and continues to kill them today. One of them, going by the name Dragonslayer, has posted many times on Shadowland with conspiracy theories about dragons.
* ''TabletopGame/{{Warhammer 40000}}'': Depending on the edition, the GodEmperor of Mankind ''was'' Myth/SaintGeorge, though instead of killing the dragon he imprisoned it on Mars. That dragon might very well be the Void Dragon, a C'tan (the C'tan are among the most powerful entities in existence, its brother the nightbringer having imposed its image into nearly all races as death incarnate, aka the GrimReaper). However, this may have bitten him in the ass, as the Void Dragon has power over machines, and it is more or less implied the Adeptus Mechanicus' worship of the Omnissiah is strengthening the Void Dragon.
* ''TabletopGame/MagicTheGathering'': [[http://gatherer.wizards.com/Pages/Card/Discussion.aspx?multiverseid=3510 Rashida Scalebane]]. Also, the [[GameBreaker infamous]] [[http://gatherer.wizards.com/Pages/Card/Details.aspx?multiverseid=205077 Baneslayer Angel]].
* HoylesRulesOfDragonPoker: In perhaps the ''only'' card game to feature both [[Myth/SaintGeorge St. Georges and Dragons]], the rivalry is alive and well.
-->25. If a St. George is played, Dragons are blank for the rest of the hand.
* ''TabletopGame/YuGiOh'' has [[http://yugioh.wikia.com/wiki/Buster_Blader Buster Blader]] and [[http://yugioh.wikia.com/wiki/Dark_Paladin Dark Paladin]], who gain ATK boosts for each opposing dragon, and [[http://yugioh.wikia.com/wiki/Dragon_Seeker Dragon Seeker]], who automatically destroys a dragon. Buster Blader can also be searched with the spell [[http://yugioh.wikia.com/wiki/Emblem_of_Dragon_Destroyer Emblem of Dragon Destroyer]]. [[http://yugioh.wikia.com/wiki/Dragon_Horn_Hunter Dragon Horn Hunter]] hunts dragons according to her flavor text.
[[folder:Video Games]]
* The Warden in ''VideoGame/DragonAgeOrigins'' fights and slays several dragons over the course of ''Origins'' and ''[[VideoGame/DragonAgeOriginsAwakening Awakening]]'', including the game's BigBad, a dragon-shaped EldritchAbomination.
** Hawke in ''VideoGame/DragonAgeII'' faces the entire gambit, ranging from Drakelings to a High Dragon. In the ''Mark of the Assassin DLC'', they're invited to take part in Duke Prosper's annual Wyvern hunt, winning a prize for being the first to slay an Alpha Wyvern. [[spoiler: Near the end, Hawke gets into a fight with Duke Prosper who in addition to using a crossbow, [[HorseOfADifferentColor rides]] into battle with his trained Wyvern, [[FluffyTheTerrible Leopold]]]].
** [[VideoGame/DragonAgeII Cassandra]] [[VideoGame/DragonAgeInquisition Pentaghast]], in addition to being a member of the current [[RoyalsWhoActuallyDoSomething royal family]] of Nevarra, descends from legendary Dragonslayers responsible for the near extinction of the entire species during the Steel Age. Pentaghast herself is no slouch, as seen in the ''Anime/DawnOfTheSeeker'' film.
** [[VideoGame/DragonAgeInquisition The Inquisitor]] and their party (which can include Cassandra) can slay a total of [[BonusBoss ten dragons]], plus [[spoiler:Corypheus's red lyrium dragon]].
* The Dragonborn in ''VideoGame/TheElderScrollsVSkyrim'' is the only one who can kill dragons permanently by consuming their souls. Others can kill them, too (in fact the Empire's SecretPolice the Blades started out as dragonslayers), but this only kills their ''body'', with their Aedric soul remaining intact. Their return from (near) extinction is revealed to have not been due to repopulating their numbers, but because [[BigBad Alduin's]] return allowed him to resurrect them from the burial mounds their remains were entombed in by the Ancient Nords.
* ''VideoGame/AdventureQuest'' and its spinoff ''VideoGame/AdventureQuestWorlds'' have this as a class designed around killing dragons and dragonkin like the {{Magitek}}-wielding Drakels.
* ''VideoGame/NeverwinterNights2'':
** Slaying the red dragon [[ThatOneBoss Tholapsyx]] in the first campaign grants you the history feat "Dragonslayer". The feat doesn't have any actual effect; it's just a cool thing to have on your resume.
** In ''Storm of Zehir'' a completionist player can slay up to four dragons, and your first dragon kill grants "Dragon Slayer". This time, though, the feat adds +2 to attack and damage rolls versus dragons.
* The eponymous characters in ''VideoGame/DragonValor'' are individuals who wield magic swords which are the only thing that can kill dragons.
* ''VideoGame/KingsBounty Legends'' has the "Dragon Slayer" spell, which enhances attack against dragons and fire resistance. Plus, the Knights can deal bonus damage to Dragons.
* In ''VideoGame/{{Drakensang}}'' Dragonslaying is a proud tradition among the dwarves, who have developed lots of special weapons (axes, hammers and large crossbows) specifically meant to kill dragons. To really drive the point home, Dwarves are said to [[LanguageEqualsThought have 18 words for "killing a dragon"]].
* In ''VideoGame/DarkSouls'', Dragon Slayer Ornstein ''earned'' the first part of his title, fighting alongside Lord Gwyn against the Everlasting Dragons in the climactic battle that allowed humanity to rise and flourish. There's a collection of dragon heads mounted in the castle in Anor Londo that provides proof of his kills. The Chosen Undead also gets the chance to slay up to five different dragons over the course of the game, and six with the DLC installed. Eight, if the hydras are included.
** It should be noted, two of those dragons were rotting zombies, two were deformed and maddened over the centuries, and one was a much lesser (though still powerful) drake. The only true dragon you face is in the DLC, and it [[spoiler: needs to be crippled by a giant's arrow]] before it can even be touched.
* ''VideoGame/PokemonXAndY'' adds the Fairy type to its ElementalRockPaperScissors system specifically to counter the Dragon type, [[ObviousRulePatch which had been getting too overpowered]].
** Oddly, before the existence of the Fairy type, ''[[LivingPolyhedron Porygon2]]'' of all Pokemon was the main go-to for dealing with dragons, possessing the ability to [[PowerCopying copy their abilities]] as well as [[GlacierWaif withstand the amount of damage they deal]], leaving surreal images of a two-foot tall toy duck taking down a seven meter tall serpent.
** Ice-types in general, even in Gen VI with the advent of Fairies.
* The arcade game Dragon Buster and it's long distance sequel VideoGame/DragonValor for the original Playstation.
* At one point in VideoGame/TheTowerOfDruaga, Gilgamesh must slay an enemy called Quox, who is essentially a dragon, even if Quox is never specifically referred to as such.
* Dirk the Daring in the first VideoGame/DragonsLair game, though not so much in the second.
[[folder:Visual Novels]]
* When the dragon shows up on Earth in ''VisualNovel/DraKoi'', a dragonslayer instantly shows up to fight her. It has no other purpose than slaying the dragon. [[spoiler:It's actually just a suit of armor and a weapon to be used by the real hero, who is the real dragonslayer. The person wielding it is called the dragon slayer or the hero: They have no name given.]]
* Neron the paladin in ''VisualNovel/SwordDaughter'' became a legend by slaying the blue dragon Slag, and a temple was built in his honor. [[spoiler:Turns out Slag's less dead than legend would have you believe, but Tyrna and Gavin can finish the job.]]
* ''Webcomic/GunnerkriggCourt'' plays with it. The official protector of the Court is called the Dragon Slayer, but James Eglamore--the current Dragon Slayer--admits that its [[ThePiratesWhoDontDoAnything a rather misleading title]]. Dragons are rare enough--if not outright extinct--that they dont require much slaying these days. Nevertheless, theres little doubt that Eglamore could take on a dragon if necessary: he defeats a Rogat Orjak ([[OurDragonsAreDifferent technically not a dragon, but very dragon-ish all the same]]) in an early chapter.
[[folder:Web Original]]
* The lore of ''LetsPlay/TwitchPlaysPokemon'' has granted this title to AATTVVV (a.k.a. [[FanNickname All-Terrain Venomoth]]) after it [[AwesomeMoments unexpectedly managed to take out Lance's Dragonite while 30 levels weaker than it]].
[[folder: Western Animation]]
* Iroh from ''WesternAnimation/AvatarTheLastAirbender'' is famed in story for slaying the last dragon left in the world earning the title Dragon of the West [[spoiler: really however he lied and left the last of the dragons alive and only claimed to have killed them so they could live in peace]].
* The film ''WesternAnimation/FireAndIce'' had a man named Galador who slew a dragon. Too bad he died years ago, and his son had to do the job. His son, while not directly killing them, manages to take care of one by pitting it against another, and the second, an ice dragon by [[spoiler: bringing down salt mines on it]].


text:
One half of homeowners already turn down their heat at night, saving
themselves 6 percent to 16 percent of heating energy. A programmable or clock thermostat can automatically do this for you.
- In addition to lowering
temperatures while you sleep, a programmable thermostat will also raise temperatures again before
you get out from under the covers.
- It not only saves energy, it's cost-effective, too. Such thermostats can be used to drop the house temperature during the day as well, if the house is unoccupied.
- "Home Energy" magazine reports savings in excess of 20 percent
with two eight-hour setbacks of 10 degrees each.
- Electronic set-back thermostats are readily available for $25 to $150.
- If you have a heat pump or central air conditioning, make sure the thermostat is designed for heat and A/C. Installation is simple, but make sure to turn off
the power to the heating plant before you begin.
- If connecting wires makes you jittery, have an electrician or heating technician do it for you. It's well worth the investment.


text:
Campaign of the Month: July 2013
Shadows Over New York
Brooklyn Botanic Garden
The Idea: Famous Botanical Gardens
The Aspect: Summer Stronghold/Portals to Summer
The Face(s): Siobahn O'Hara (Changeling Park Ranger)
Founded in 1910, Brooklyn Botanic Garden (BBG) is an independent nonprofit institution committed to education, research, and the display of horticulture. BBG serves communities in New York City and internationally through its world-class gardens, extensive research collections, and numerous educational and community programs. Situated on 52 acres in the heart of Brooklyn, the Garden is home to over 10,000 types of plants and hosts more than 700,000 visitors annually.
The BBG is overseen by Siobahn O'Hara, Park Ranger and Changeling Daughter of Lily (The Summer Lady) and is a firm stronghold of power for the Summer Court within NYC, containing no less than 6 separate portals to various parts of Summer.


text:
Looking goodThe West Midlands was the cradle for the first Industrial Revolution. Today, 200 years later, the region is shaping the second.
A fresh perspectivePost-industrial decline hit the West Midlands hard. It is now a vibrant and dynamic region, yet it still struggles to shake off its bleak image. Chris Arnot finds another side of the story.
Front page
Opinion: is the West Midlands a good place to live, work and study?Carol Undy, was previously Chair of the Federation of Small Businesses. She used to own a road haulage firm with a turnover of more than £3m. She now runs a commercial property company in Coventry and Rugby
And now for something completely differentOnce famed for its manufacturing, the West Midlands is increasingly being recognised as home to a new kind of industry: ICT
Guardian extra p2
'This century we can be world beaters'Liam Byrne
The right ingredients for growthBased in West Bromwich, near Birmingham, East End Foods is one of the largest UK importers of Indian foods. "We started off in Wolverhampton in the 1970s and we have no plans to leave the West Midlands whatsoever," says Tony Deep Wouhra, chairman of the company and one of four brothers behind the business.
Life in the fast laneTim Watts has an unequivocal view of the technological and industrial potential of the West Midlands. "It is our history. This place has been a centre of innovation for the past 200 years. It is in our blood to invent and build machines," says Watts, chairman of Pertemps and an expert on manufacturing and innovation in the West Midlands.
Finance scheme lends SMEs a helping handSmall and medium-sized enterprises (SMEs) in the West Midlands struggling to raise finances for their businesses can turn to Advantage West Midland's Access to Finance initiatives for assistance.
Guardian extra p4
A city with something to shout aboutBirmingham is clawing its way back from the recession of the 1980s, while extensive urban regeneration is helping to transform the city's image.
Guardian extra p6
Cottage industry, but not as we know itThe West Midlands' new economic pulse beats from the farms and hamlets nestled among its vast acres of green land.
Picturesque countryside right on your doorstepOutside of its urban cities, the West Midlands is home to some of the UK's prettiest beauty spots.