Caltech Biologists Pursue Promising New Approach in Treatment of HIV/AIDS and Cancer

PASADENA, Calif.—In response to the arduously slow progress in finding cures for AIDS and cancer, Caltech researchers are now investigating a promising new approach in the treatment of these diseases.

With a $1.5 million matching grant from the Skirball Foundation in New York, Caltech biologists have established the Engineering Immunity project, designed to create a novel immunological approach to treating–and even some day preventing–HIV infection and some cancers like melanoma.

The immune system provides humans with a powerful defense against infectious diseases–but sometimes, it fails. Utilizing an innovative, integrated approach, the Engineering Immunity project will combine gene therapy, stem cell biology, and immunotherapy to arm the immune system; this integrative methodology offers groundbreaking potential for treatment of these diseases and others for which the immune system currently fails to provide defense.

Caltech President David Baltimore, who won the Nobel Prize in 1975 for his work in virology and cancer research, stated, "The Engineering Immunity project advocates a new approach to therapy for AIDS and cancer with revolutionary implications for the treatment of these and many other diseases. It is an innovative research project that holds special significance for the future of biomedical sciences."

In the fight against HIV, the virus that causes AIDS, T-cell immunity and T-cell-focused therapies and vaccines have been methods widely investigated and pursued. However, antibodies often provide the best protection against viruses, and virtually all vaccines for other viral diseases are designed to elicit antibody-based immunity. Antibodies against HIV do appear during HIV infections, but heretofore, they had not been able to provide therapeutic advantage to most patients. Rare neutralizing antibodies have been identified, but have not proven valuable because a general way to elicit their production in all patients has not been found. Moreover, most of them are effective only at very high concentrations that are hard to maintain in a person by conventional means. Thus, early attempts to elicit antibody-based immunity against HIV have largely failed.

The Engineering Immunity integrated methodology involves utilizing retroviruses, which are natural carriers of genes. Retrovirus vectors will be produced that encode antibodies found to be effective against HIV. Utilizing retroviruses, the Baltimore Laboratory at Caltech, in collaboration with Caltech structural biologist Pamela Bjorkman, will introduce specific genes into stem cells. These genes will encode specificity molecules on the immune cells, thereby arming the immune cells to kill selected agents or cells, i.e., the cells that are growing HIV or particular cancer cells.

The Engineering Immunity initiative will provide a new route to the production of antibodies with therapeutic, and even protective, ability for a potential cure of AIDS, melanoma, and other diseases ultimately.

The Skirball Foundation, an independent foundation created in 1950 by Jack H. Skirball, is dedicated primarily to medical research and care, educational and social needs of disadvantaged children, and advancing the highest values of the Jewish heritage. Among the many institutions that the Foundation has supported are the Skirball Cultural Center, the Salk Institute, the Venice Family Clinic, the Jewish Childcare Association in New York City, and the Skirball Institute of Biomolecular Medicine at New York University.

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Contact: Deborah Williams-Hedges (626) 395-3227 debwms@caltech.edu

Visit the Caltech Media Relations Web site at: http://pr.caltech.edu/media

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Fuel Cells: the Next Generation

PASADENA, Calif. — For several years now the Department of Energy (DOE) has been urging the fuel cell community to solve a major problem in the design of solid oxide fuel cells (SOFCs): heat. Such fuel cells could someday provide reliable power for homes and industry, dramatically cutting greenhouse gas emissions as well as other pollutants.

But SOFCs run hot, at temperatures as high as 1000 degrees Celsius (about 1800 degrees Fahrenheit). They're efficient at such temperatures, but only a few costly materials can withstand the heat. Using such materials makes things expensive, and is the reason for the push for lower temperatures by the DOE.

Sossina Haile, an associate professor of materials science and chemical engineering at the California Institute of Technology, is an expert in fuel cells, and she has been whittling away at the heat problem for years. Now she and her colleagues have not only solved the problem, they've smashed it. They've brought the temperature down to about 600 degrees Celsius (1100 degrees Fahrenheit), while achieving more power output than others are achieving at the higher temperatures--about 1 watt per square centimeter of fuel cell area.

They accomplished this by changing the chemical composition of one component of a fuel cell called the cathode. The cathode is where air is fed in to the fuel cell, and it's where the oxygen is electrochemically reduced to oxygen ions. The oxygen ions then migrate across the electrolyte (which conducts electricity), to react with fuel at the anode, another fuel cell component. The electrochemical reduction of oxygen is an essential step in the fuel cell's process of generating power. But the problem with running solid oxide fuel cells at 500 to 700 degrees Celsius is that the cathode becomes inactive when the temperature is less than about 800 degrees Celsius.

Haile and postdoctoral scholar Zongping Shao's insight was to switch out the conventional cathode and replace it with a compound that has a long chemical formula guaranteed to strike fear into the heart of every undergraduate, but is abbreviated as "BSCF" for short.

What BSCF can do that standard cathodes can't is to allow the oxygen to diffuse through it very rapidly. "In conventional cathodes, the oxygen diffuses slowly, so that even if the electrochemical reaction is fast, the oxygen ions are slow in getting to the electrolyte," says Haile. "In BSCF the electrochemical reaction is fast and the oxygen ion transport is fast. You have the best combination of properties." This combination is what gives the very high power outputs from Haile's fuel cells.

The work was reported in a recent issue of the journal Nature. Because they are using relatively conventional anodes and electrolytes with this new cathode, says Haile, it would be easy to switch out cathodes in existing fuel cells. That will probably be their next step, says Haile: to partner with a company to produce the next generation of solid-oxide fuel cells.

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CBI Reveals Motion in the Remotest Seeds of Galaxy Clusters in the Very Early Universe

PASADENA, Calif.--Cosmologists from the California Institute of Technology have used observations probing back to the remote epoch of the universe when atoms were first forming to detect movements among the seeds that gave rise to clusters of galaxies. The new results show the motion of primordial matter on its way to forming galaxy clusters and superclusters. The observations were obtained with an instrument high in the Chilean Andes known as the Cosmic Background Imager (CBI), and they provide new confidence in the accuracy of the standard model of the early universe in which rapid inflation occurred a brief instant after the Big Bang.

The novel feature of these polarization observations is that they reveal directly the seeds of galaxy clusters and their motions as they proceeded to form the first clusters of galaxies.

Reporting in the October 7 online edition of Science Express, Caltech's Rawn Professor of Astronomy, and principal investigator on the CBI project, Anthony Readhead and his team say the new polarization results provide strong support for the standard model of the universe as a place in which dark matter and dark energy are much more prevalent than everyday matter as we know it, which poses a major problem for physics. A companion paper describing early polarization observations with the CBI has been submitted to the Astrophysical Journal.

The cosmic background observed by the CBI originates from the era just 400,000 years after the Big Bang and provides a wealth of information on the nature of the universe. At this remote epoch none of the familiar structures of the universe existed--there were no galaxies, stars, or planets. Instead there were only tiny density fluctuations, and these were the seeds out of which galaxies and stars formed under the hand of gravity.

Instruments prior to the CBI had detected fluctuations on large angular scales, corresponding to masses much larger than superclusters of galaxies. The high resolution of the CBI allowed the seeds of the structures we observe around us in the universe today to be observed for the first time in January 2000.

The expanding universe cooled and by 400,000 years after the Big Bang it was cool enough for electrons and protons to combine to form atoms. Prior to this time photons could not travel far before colliding with an electron, and the universe was like a dense fog, but at this point the universe became transparent and since that time the photons have streamed freely across the universe to reach our telescopes today, 13.8 billion years later. Thus observations of the microwave background provide a snapshot of the universe as it was just 400,000 years after the Big Bang--long before the formation of the first galaxies, stars, and planets.

The new data were collected by the CBI between September 2002 and May 2004, and cover four patches of sky, encompassing a total area three hundred times the size of the moon and showing fine details only a fraction of the size of the moon. The new results are based on a property of light called polarization. This is a property that can be demonstrated easily with a pair of polarizing sunglasses. If one looks at light reflected off a pond through such sunglasses and then rotates the sunglasses, one sees the reflected light varying in brightness. This is because the reflected light is polarized, and the polarizing sunglasses only transmit light whose polarization is properly aligned with the glasses. The CBI likewise picks out the polarized light, and it is the details of this light that reveal the motion of the seeds of galaxy clusters.

In the total intensity we see a series of peaks and valleys, where the peaks are successive harmonics of a fundamental "tone." In the polarized emission we also see a series of peaks and valleys, but the peaks in the polarized emission coincide with the valleys in the total intensity, and vice versa. In other words, the polarized emission is exactly out of step with the total intensity. This property of the polarized emission being out of step with the total intensity indicates that the polarized emission arises from the motion of the material.

The first detection of polarized emission by the Degree Angular Scale Interferometer (DASI), the sister project of the CBI, in 2002 provided dramatic evidence of motion in the early universe, as did the measurements by the Wilkinson Microwave Anisotropy Probe (WMAP) in 2003. The CBI results announced today significantly augment these earlier findings by demonstrating directly, and on the small scales corresponding to galaxy clusters, that the polarized emission is out of step with the total intensity.

Other data on the cosmic microwave background polarization were released just two weeks ago by the DASI team, whose three years of results show further compelling evidence that the polarization is indeed due to the cosmic background and is not contaminated by radiation from the Milky Way. The results of these two sister projects therefore complement each other beautifully, as was the intention of Readhead and John Carlstrom, the principal investigator of DASI and a coauthor on the CBI paper, when they planned these two instruments a decade ago.

According to Readhead, "Physics has no satisfactory explanation for the dark energy which dominates the universe. This problem presents the most serious challenge to fundamental physics since the quantum and relativistic revolutions of a century ago. The successes of these polarization experiments give confidence in our ability to probe fine details of the polarized cosmic background, which will eventually throw light on the nature of this dark energy."

"The success of these polarization experiments has opened a new window for exploring the universe which may allow us to probe the first instants of the universe through observations of gravitational waves from the epoch of inflation," says Carlstrom.

The analysis of the CBI data is carried out in collaboration with groups at the National Radio Astronomy Observatory (NRAO) and at the Canadian Institute for Theoretical Astrophysics (CITA).

"This is truly an exciting time in cosmological research, with a remarkable convergence of theory and observation, a universe full of mysteries such as dark matter and dark energy, and a fantastic array of new technology--there is tremendous potential for fundamental discoveries here" says Steve Myers of the NRAO, a coauthor and key member of the CBI team from its inception.

According to Richard Bond, director of CITA and a coauthor of the paper, "As a theorist in the early eighties, when we were first showing that the magnitude of the cosmic microwave background polarization would likely be a factor of a hundred down in power from the minute temperature variations that were themselves a heroic effort to discover, it seemed wishful thinking that even in some far distant future such minute signals would be revealed. With these polarization detections, the wished-for has become reality, thanks to remarkable technological advances in experiments such as CBI. It has been our privilege at CITA to be fully engaged as members of the CBI team in unveiling these signals and interpreting their cosmological significance for what has emerged as the standard model of cosmic structure formation and evolution."

The next step for Readhead and his CBI team will be to refine these polarization observations significantly by taking more data, and to test whether or not the polarized emission is exactly out of step with the total intensity with the goal of finding some clues to the nature of the dark matter and dark energy.

The CBI is a microwave telescope array comprising 13 separate antennas, each about three feet in diameter and operating in 10 frequency channels, set up in concert so that the entire instruments acts as a set of 780 interferometers. The CBI is located at Llano de Chajnantor, a high plateau in Chile at 16,800 feet, making it by far the most sophisticated scientific instrument ever used at such high altitudes. The telescope is so high, in fact, that members of the scientific team must each carry bottled oxygen to do the work.

The upgrade of the CBI to polarization capability was supported by a generous grant from the Kavli Operating Institute, and the project is also the grateful recipient of continuing support from Barbara and Stanley Rawn Jr. The CBI is also supported by the National Science Foundation, the California Institute of Technology, and the Canadian Institute for Advanced Research, and has also received generous support from Maxine and Ronald Linde, Cecil and Sally Drinkward, and the Kavli Institute for Cosmological Physics at the University of Chicago.

In addition to the scientists mentioned above, today's Science Express paper is coauthored by C. Contaldi and J. L. Sievers of CITA, J.K. Cartwright and S. Padin, both of Caltech and the University of Chicago; B. S. Mason and M. Pospieszalski of the NRAO; C. Achermann, P. Altamirano, L. Bronfman, S. Casassus, and J. May all of the University of Chile; C. Dickinson, J. Kovac, T. J. Pearson, and M. Shepherd of Caltech; W. L. Holzapfel of UC Berkeley; E. M. Leitch and C. Pryke of the University of Chicago; D. Pogosyan of the University of Toronto and the University of Alberta; and R. Bustos, R. Reeves, and S. Torres of the University of Concepción, Chile.

 

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Memory Lane in the Brain

PASADENA, Calif.- Biologist Erin Schuman is interested in how memories are formed--or forgotten. The landscape the professor of biology at the California Institute of Technology explores is the hippocampus, the part of the brain known to be crucial for memory in humans and other animals.

In 2002, Schuman and Miguel Remondes, her graduate student, published a paper in the journal Nature that suggested a possible role for a well-known but poorly understood part of the brain known as the temporoammonic (TA) pathway. Using rat hippocampal slices, they suggested two possible roles for the TA pathway that were not previously known: to serve as a memory gatekeeper that can either enhance or diminish memories, and to provide information to help animals know where they are in their environments.

The researchers' next step was to prove their theories by looking at a possible role for the TA in memory at a behavioral level. That is, says Remondes, now a postdoctoral fellow at MIT, "to do the real test."

To understand how memories are formed, many scientists have focused on the "trisynaptic circuit," which involves three areas of the hippocampus: input from the senses is first sent from the cortex to the dentate gyrus, where this signal is processed by two sets of synapses, then sent back to the cortex. That's the circuit. An often overlooked separate input to the hippocampus, though, is the TA pathway. It makes direct contact with the neurons that are at the last station in the trisynaptic circuit, thus short-circuiting the traditional trisynaptic pathway.

Reporting in the October 7 issue of the journal Nature, Remondes and Schuman, also an associate investigator for the Howard Hughes Medical Institute, now show they were correct in their belief that the TA Pathway is important in spatial or location memory. The scientists used rats as their experimental animal, and the Morris Water Maze, a standard test for location memory in rodents. The animals swim in a pool of opaque water until they find a hidden goal--a platform which allows them to escape the water. To find the platform, the animals rely on the geometrical relationships of cues away from the pool (e.g., on the walls of the maze). In other words, says Remondes, "they have to navigate and remember where the platform is in order to escape the water."

The researchers tested both short-term (24 hours) and long-term memory (four weeks). The TA pathway was lesioned (disabled) in one set of rats; another set was used as a control. Having learned the location of the platform, both sets of rats still remembered where it was 24 hours later. But when tested four weeks later, only the control rats remembered where it was. The lesioned rats forgot, which showed that the TA pathway played some role in the retention of long-term memories. But what was the role?

"It led to a second question," says Schuman. "Because long-term memories require something called consolidation, an exchange of information between the cortex and hippocampus, we wanted to know if the TA pathway was working in the acquisition phase of memory or in its consolidation."

Using two other groups of rats, the pair conducted a second set of tests. After confirming the rat's memory of the platform after 24 hours, one group was immediately lesioned. These animals lost their long-term memory when tested 4 weeks later, indicating to Schuman and Remondes that ongoing TA pathway activity was required on days after learning to stabilize or consolidate the long-term memory.

The second group of rats was also lesioned, but not until three weeks later. The researchers found that this group remembered the platform's location, showing their memory had already been adequately consolidated after three weeks. This proved the TA pathway is required to consolidate long-term location memory.

"These data indicate there must be a dialogue between the hippocampus and the cortex during long-term memory consolidation," says Schuman. "Clearly, the TA pathway plays an important role in this discussion." Further, she notes, "understanding the mechanisms of memory formation and retention may shed light on diseases like Alzheimers, where memory is impaired. "

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New Target for Future Therapeutic Drugs

PASADENA, Calif. - "Sometimes letting nature tell you what's important is the better way to go," says Raymond Deshaies, an associate professor of biology at the California Institute of Technology. Deshaies is referring to new work to come out of his lab and the lab of Randall King at Harvard that defies conventional thinking--they've discovered a chemical that stops a key cell function, but, more importantly, suggests a new possible target within a cell, once thought to be untenable, for future therapeutic drugs.

In a report in this week's issue of the journal Science, lead author Rati Verma, a Howard Hughes Medical Institute (HHMI) Research Specialist in the Deshaies lab, Deshaies, also an assistant investigator for the HHMI, and nine other authors report that a small molecule called ubistatin blocked an important step in the so-called cell cycle, a process fundamental to life where a cell makes duplicate copies of its own DNA for distribution to two daughter cells. Knowing how to stop cell duplication is critical in preventing diseases like cancer, when mutated cells go out of control and proliferate madly. Further, ubistatin blocked the cell cycle by preventing two proteins from interacting together. Prior to this, it was thought unlikely that a compound with low molecular weight like ubistatin--or any future drug--would have much impact on the interaction of proteins with each other.

While ubistatin has other properties that preclude it from being a drug candidate, its stoppage of the cell cycle provides an important clue for future drug development, says Deshaies. "We've found a chemical Achilles' heel in this cell pathway, at least from the viewpoint of these small molecules that comprise most therapeutic drugs."

Because the cell cycle is maddeningly complex, researchers usually pick a single pathway (a pathway is a series of chemical events within a cell that perform some task), then try to make a chemical to block it. They may find such a chemical, but often find it difficult to discover where in the pathway--the target--their drug hit. Finding the target is like finding the proverbial needle in a haystack.

Deshaies's colleague Rati Verma found the needle. Instead of using the typical "top down" approach of starting with a specific target, then looking for a drug to block it, the researchers took a "bottom up" approach of starting with a drug and then searching for the target it blocks. They decided to test a large number of molecules to see if any of them might block any step in one particular pathway called the ubiquitin-proteasome pathway (UP pathway): within the cell cycle, when a protein's job is done, another chain of proteins called ubiquitin attaches to it. That serves as a signal to yet another protein called proteasome. The proteasome, says Deshaies, is the biological equivalent of a Cuisinart. "It attaches to these ubiquitin-marked proteins, then ingests them and chews them up."

The researchers examined an entire cell, specifically that of a frog's egg. The King group decided to screen 110,000 molecules to see if any had an impact on the cell. First, they weeded out those molecules that had no effect on cellular function in the UP pathway. King attached a molecule of luciferase ("the stuff that makes a firefly light up," says Deshaies) to certain proteins that are normally destroyed during cell division. Next, he added this newly created protein (now a readily detectable biological "flashlight") to droplets of cellular material extracted from the frog's egg that had been placed in individual chambers. As the egg extract conducted its normal cell division, the luciferase flashlight was destroyed and the chambers went dark. That meant those proteins had been destroyed as part of the normal progress of the cell cycle. He then separately added the 110,000 small molecules to see if any of them would prevent the loss of the luciferase--essentially looking for a lit-up reaction chamber in a field of darkness.

Using this approach, the researchers eventually narrowed the molecules they were testing down to a few that were operating in a specific part of the pathway--downstream from where ubiquitin attaches to the soon-to-be doomed protein, but before the proteasome ingested and chewed it up. But given that numerous proteins are involved in this process, the question remained--where specifically was the molecule they were testing working? In short, where was the target?

To find out, Deshaies turned to work they had done over the last five years with ubiquitin, which examined how it interacted with various other proteins, including proteasome. Through a process of elimination, says Deshaies, "we figured out that these small molecules called ubistatins were blocking the recognition of the ubiquitin chain by the proteasome." Graphic evidence for how this occurs was provided by a 'picture' taken by David Fushman at the University of Maryland with a nuclear magnetic resonance spectrometer.

This step blocked by ubistatin involves a protein-protein interaction, a surprise to Deshaies. "One interesting thing about our discovery is that it is further evidence that you can affect a protein-protein interaction with a small molecule. The conventional thinking was that if you look at a footprint of a drug binding a protein, the drugs are small, but the footprint that corresponds to one protein binding to another is big. So most people thought that the idea of trying to block the huge footprint of protein-protein interaction with a tiny drug was extremely unlikely. So if I were asked to predict what we would find, I would never have proposed that a drug could prevent the ubiquitin chain from binding to the proteasome, because I was also influenced by this conventional wisdom."

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Caltech Bioinformatics Experts DevelopNew Literature Search Engine for Biologists

PASADENA, Calif.—When it comes to finding a used book on the Internet, one merely needs to Google the title, and a few suitable items for sale will soon be just a click away. But for the biologist or medical researcher looking for information on how two nematode genes interrelate in hopes of better understanding human disease, there is a clear need for a more focused search engine.

Bioinformatics experts from the California Institute of Technology are formally announcing today the Textpresso search engine, which they hope will revolutionize the way that genetic information is retrieved by researchers worldwide. The Textpresso search engine is specifically built to serve researchers who work on the small worm known as C. elegans, but the basic design should lead to the creation of new search engines for researchers who specialize in other living organisms that are intensively studied.

In the current issue of the journal PLOS, published by the Public Library of Science, Caltech biology professor Paul Sternberg and his colleagues--research associate Hans-Michael Muller and bioinformatics specialist Eimear Kenny--write that the new "text-mining system for scientific literature" will be invaluable to specialists trying to cope with the vast amount of information now available on C. elegans. This information has vastly increased in recent years due to the large-scale gene-sequencing initiative as well as the more traditional small-scale projects by individual researchers. As a result, the need for a way to scan the vast literature has become much more important.

"Textpresso gives me, as a researcher, more time to actually read papers because I don't have to skim papers anymore," says Sternberg, who is leader of the federally funded WormBase project that has already put online the entire genome sequence of C. elegans and the closely related organism C. briggsae, as well as genes for some 20 other nematode species.

The four-year-old WormBase project, a linchpin in the worldwide effort to better understand how genes interrelate, also makes a host of other information freely available in addition to the 100.2 million base-pairs that make up the millimeter-long worm's genome. There are now 28,000 gene-disruption experiments in WormBase, along with 2 million DNA expression ("chip") microarray observations, as well as detailed information on the expression of more than 1,700 of the worm's 20,000 genes. The Textpresso search engine is a logical product for the WormBase team to develop in the ongoing quest to put genetic information to work in curing and preventing human disease.

Lest anyone assume that the genes of a millimeter-long nematode have little to do with humans, it should be pointed out that the two organisms are similar in about 40 percent of their genes. A very realistic motivation for funding the genome sequencing of the fruit fly, the small mustardlike plant known as Arabidopsis, the chimp, and various other species, has been the expectation of finding underlying common mechanisms.

Thus, a cancer researcher who discovers that a certain gene is expressed in cancer cells can use the WormBase to see if the gene exists in nematodes, and if so, what is known about the gene's function. And now that Textpresso is available, the researcher can do so much more efficiently.

"The idea is distilling down the information so it can be extracted easier," says Muller, the lead author of the paper and codeveloper of Textpresso with Kenny. The idea for the name of the search engine, in fact, comes from its resemblance to "espresso," which is a process used to get the caffeine and flavor out of coffee in a minimal volume.

According to Kenny, the search engine is designed with a special kind of search in mind, which establishes categories of terms and organizes them as an ontology--that is, a catalog of types of objects and concepts and their relationships. For example, if the researcher wants to find out whether any other researcher has worked on the relationship between the nematode gene called "lin-12" and the anchor cell, then typing the two terms into a conventional search engine like Google results in more than 400 hits. And if the researcher wants to know which genes are important in the anchor cell, the task is even more arduous. But Textpresso is designed to get the information in a much simpler, more efficient, more straightforward way.

Textpresso is a text-processing system that splits research papers into sentences, and sentences into words or phrases. All words and phrases are labeled so that they are searchable, and the labels are then condensed into 33 ontological categories. So far, the database includes 4,420 scientific papers on C. elegans, as well as bibliographic information from WormBase, information on various scientific meetings, the "Worm Breeder's Gazette," and various other links and WormBase information. Therefore, the engine already searches through millions of sentences to allow researchers to find a paper of interest or information of interest with great efficiency.

Finally, the Textpresso search engine should be a useful prototype for search engines to serve other biological databases--some of which have even larger piles of data for the specialist to cope with. "Yeast currently has 25,000 papers," Kenny says.

Textpresso can be accessed at www.textpresso.org or via WormBase at www.wormbase.org.

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Robert Tindol
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Research uncovers new facts about odor detection in insects; findings could lead to more effective repellents

PASADENA, Calif.--If you think it doesn't do much good to swipe the fly that's going after the potato salad, guess again. You may be discouraging the fly's colleagues from taking up the raid.

New evidence shows that a stressed fly emits an odor that makes other flies avoid the space in which the stressful event occurred. Reporting in an advance on-line publication of the September 15 issue of the journal Nature, California Institute of Technology professors David Anderson and Seymour Benzer, along with Professor Richard Axel of Columbia University, discuss their findings about how flies may communicate information about their internal state to one another.

According to the authors, the act of shaking or shocking flies causes a repellent odor to be emitted that contains carbon dioxide as one of its active components. The research involved the fruit fly, Drosophila melanogaster, which has been used for decades in genetics experiments. However, the mechanism could be more widespread.

"We showed that CO2 is itself a potent repellent for Drosophila," says Anderson, a professor of biology at Caltech and also a Howard Hughes Medical Institute investigator.

The researchers also succeeded in mapping the initial neural circuitry that leads to CO2 avoidance. The team, led by Caltech postdoctoral scholar Greg Suh, found that CO2 activates a single class of sensory neurons in the fruit flies, and that these neurons seem to be dedicated to the sole task of responding to this odor. By inhibiting the synapses of these neurons using fancy genetic trickery, the researchers were able to block the ability of flies to avoid CO2, in behavioral experiments.

"These results show that there is probably a genetically determined, or 'hard-wired' circuit mediating CO2 avoidance behavior in the fly," Anderson says.

But even though the research is primarily aimed at furthering the understanding of the neural circuitry underlying innate behaviors, there might also be practical results. For one, the fact that mosquitoes are attracted to their warm-blooded hosts by CO2 exhalations has been known for years.

Although fruit flies are repelled by CO2, while mosquitoes are attracted to it, "given the evolutionary conservation of olfactory mechanisms in insects, if we learn about the molecular details involved in CO2 sensing in fruit flies, it could potentially lead to repellents that act by interfering with the reception of CO2," Anderson adds.

Such a repellent could be of benefit in third-world countries where mosquitoes are vectors of diseases like malaria--or even in the United States, where the mosquito-borne West Nile virus has been a serious health concern this year.

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Caltech Physicists Achieve Measurement on a Single Magnetic Domain Wall

PASADENA, Calif.--Physicists for several years have been predicting a new age of semiconductor devices that operate by subtle changes in the orientation of electron spins. Known as "spintronics," the field relies on an intricate knowledge of the magnetic properties of materials and of how magnetic moments can be manipulated.

Now, scientists at the California Institute of Technology have developed a novel method of measuring the resistance of "domain walls," which are the nanoscale boundaries separating areas of a magnetized material that possess different magnetic alignments, or a "twist" of magnetic spins. Reporting in the September 2 issue of the journal Nature, Caltech physicists Hongxing Tang, Michael Roukes, and their colleagues show that their approach leads to an unparalleled precision in isolating, manipulating, and trapping domain walls one by one.

The authors have been able to trap individual domain walls between electrical probes for periods longer than a week. During that time, they are able to carry out extremely sensitive electrical measurements to identify the tiny amounts of resistance generated by this trapped single magnetic domain wall.

"We have demonstrated how a single magnetic domain wall can be monitored as it is made to traverse a patterned array of electrical probes in a microdevice made from single-crystal manganese-doped gallium arsenide," says Professor Roukes. Manganese- doped gallium arsenide belongs to a new class of ferromagnetic semiconductors that isexpected to have great potential for new spintronics devices.

This work also resolves an issue that has puzzled scientists for some time, according to Tang. Many physicists have thought that domain walls were a natural barrier to electron transport and that they cause positive resistance--in other words, the magnetic moments with different alignments created a natural opposition to the flow of charge from one side of the wall to the other. However, the new results show that the resistance is actually negative, which can be attributed to quantum effects in the locale of the domain wall itself. The very fact that the resistance is negative means that electrons can flow more easily under certain conditions, manifesting quantum mechanical origin in this novel phenomenon.

"We are certain that both this result and our new measurement methodology will be of interest to those working on future semiconductor devices based on spintronics," Tang says.

Understanding the dynamics of magnetic domain walls is crucial for magnetic storage devices such as magnetic hard drives, and for future magnetic memories. The methods have the potential to significantly alter the theoretical and experimental research for some time to come.

The work has been made possible through the Caltech team's earlier discovery of a phenomenon dubbed the "giant planar Hall effect." To reach the ultra-high resolution required to resolve the resistance of a domain wall, the authors advance a nanofabrication process for precise alignments of materials at the microscopic level and deploy an innovative way of manipulating domain walls.

"Using these advances, we have made careful measurements on many devices having domain walls of varying lengths and thicknesses," says Roukes. "All show negative resistance at the domain wall."

In addition to being a professor of physics, applied physics, and bioengineering at Caltech, Roukes is also founding director of Caltech's new Kavli Nanoscience Institute. Dr. Hongxing Tang is a senior research scientist at Caltech. Other authors of the paper are Sotiris Masmanidis, a Caltech graduate student in applied physics, and Roland Kawakami and Prof. David Awschalom, both of the UC Santa Barbara department of physics.

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Robert Tindol

International Team of Scientists Establishes New Internet Land-Speed Benchmark

PASADENA, Calif.—Scientists at the California Institute of Technology (Caltech) and the European Organization for Nuclear Research (CERN), along with colleagues at AMD, Cisco, Microsoft Research, Newisys, and S2io have set a new Internet2 land-speed record. The team transferred 859 gigabytes of data in less than 17 minutes at a rate of 6.63 gigabits per second between the CERN facility in Geneva, Switzerland, and Caltech in Pasadena, California, a distance of more than 15,766 kilometers. The speed is equivalent to transferring a full-length DVD movie in just four seconds.

The technology used in setting this record included S2io's Xframe® 10 GbE server adapter, Cisco 7600 Series Routers, Newisys 4300 servers utilizing AMD Opteron processors, Itanium servers, and the 64-bit version of Windows Server 2003.

The performance is also remarkable because it is the first record to break the 100 petabit meter per second mark. One petabit is 1,000,000,000,000,000 bits.

This latest record by Caltech and CERN is a further step in an ongoing research-and-development program to create high-speed global networks as the foundation of next-generation data-intensive grids.

Multi-gigabit-per-second IPv4 and IPv6 end-to-end network performance will lead to new research and business models. People will be able to form "virtual organizations" of planetary scale, sharing in a flexible way their collective computing and data resources. In particular, this is vital for projects on the frontiers of science and engineering, projects such as particle physics, astronomy, bioinformatics, global climate modeling, and seismology.

Harvey Newman, professor of physics at Caltech, said, "This is a major milestone towards our dynamic vision of globally distributed analysis in data-intensive, next-generation high-energy physics (HEP) experiments. Terabyte-scale data transfers on demand, by hundreds of small groups and thousands of scientists and students spread around the world, is a basic element of this vision; one that our recent records show is realistic." Olivier Martin, head of external networking at CERN and manager of the DataTAG project said, "As of 2007, when the Large Hadron Collider, currently being built at CERN, is switched on, this huge facility will produce some 15 petabytes of data a year, which will be stored and analyzed on a global grid of computer centers. This new record is a major step on the way to providing the sort of networking solutions that can deal with this much data."

The team used the optical networking capabilities of the LHCnet, DataTAG, and StarLight and gratefully acknowledges support from the DataTAG project sponsored by the European Commission (EU Grant IST-2001-32459), the DOE Office of Science, High Energy and Nuclear Physics Division (DOE Grants DE-FG03-92-ER40701 and DE-FC02-01ER25459), and the National Science Foundation (Grants ANI 9730202, ANI-0230967, and PHY-0122557).

About Caltech:

With an outstanding faculty, including three Nobel laureates, and such off-campus facilities as Palomar Observatory, and the W. M. Keck Observatory, the California Institute of Technology is one of the world's major research centers. The Institute also conducts instruction in science and engineering for a student body of approximately 900 undergraduates and 1,000 graduate students who maintain a high level of scholarship and intellectual achievement. Caltech's 124-acre campus is situated in Pasadena, California, a city of 135,000 at the foot of the San Gabriel Mountains, about 10 miles northeast of the Los Angeles Civic Center. Caltech is an independent, privately supported university. More information is available at http://www.caltech.edu.

About CERN:

CERN, the European Organization for Nuclear Research, has its headquarters in Geneva, Switzerland. At present, its member states are Austria, Belgium, Bulgaria, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Slovakia, Spain, Sweden, Switzerland, and the United Kingdom. Israel, Japan, the Russian Federation, the United States of America, Turkey, the European Commission, and UNESCO have observer status. For more information, see http://www.cern.ch.

About the European Union DataTAG project:

The DataTAG is a project co-funded by the European Union, the U.S. Department of Energy, and the National Science Foundation. It is led by CERN together with four other partners. The project brings together the following European leading research agencies: Italy's Istituto Nazionale di Fisica Nucleare (INFN), France's Institut National de Recherche en Informatique et en Automatique (INRIA), the UK's Particle Physics and Astronomy Research Council (PPARC), and Holland's University of Amsterdam (UvA). The DataTAG project is very closely associated with the European Union DataGrid project, the largest grid project in Europe also led by CERN. For more information, see http://www.datatag.org.

Writer: 
Robert Tindol
Writer: 

Geobiologists create novel method for studying ancient life forms

PASADENA, Calif.--Geobiologists are announcing today their first major success in using a novel method of "growing" bacteria-infested rocks in order to study early life forms. The research could be a significant tool for use in better understanding the history of life on Earth, and perhaps could also be useful in astrobiology.

Reporting in the August 23 edition of the journal Geology, California Institute of Technology geobiology graduate student Tanja Bosak and her coauthors describe their success in growing calcite crusts in the presence and absence of a certain bacterium in order to show that tiny pores found in such rocks can be definitively attributed to microbial presence. Micropores have long been known to exist in certain types of carbonate rocks that built up in the oceans millions of years ago, but researchers have never been able to say much more than that the pores were likely caused by microbes.

The new results show that there is a definite link between microbes and micropores. In the experiment, Bosak and her colleagues grew a bacterium known as Desulfovibrio desulfuricans in a supply of nutrients, calcium, and bicarbonate that built up just like a carbonate deposit in the ancient oceans. The mix that contained the bacteria tended to form rock with micropores in recognizable patterns, while the "sterile" mix did not.

"Ours is a very reductionist approach," says Dianne Newman, the Clare Boothe Luce Assistant Professor of Geobiology and Environmental Science and Engineering at Caltech and a coauthor of the paper. "This work shows that you can study a single species to see how it behaves in a controlled environment, and from that draw conclusions that apply to the rock record. The counterpart is to go to nature and infer what's going on in a system you can't control."

"We were primarily interested in directly observing how the microbes disrupt the crystal growth of the carbonate rocks," adds Bosak. In essence, the microbes are large enough to displace a bit of "real estate" with their bodies, resulting in a tiny cavity that is left behind in the permanent record. The micropores in the study tend to be present throughout the crystals, and they not only mirror the shape and size of the bacteria, but also tend to form characteristic swirling patterns. If the micropores had been formed by some kind of nonliving particles, the patterns would likely not be present.

The next step in the research is to run the growth experiments with photosynthetic microbes. The information could help scientists determine which shapes found in certain types of rocks can be used as evidence of early life on Earth. In the future, the information could also be used to study samples from other rocky planets and moons for evidence of primitive life.

Primarily, however, Newman says the technique will be of immediate benefit in studying Earth. "If you really want to look at life billions of years ago, in the Precambrian, you need to study microbial life.

"Even today the diversity of life is predominantly microbial," Newman adds, "so if we expand our perspective of what life is beyond macroscopic organisms, it's clear that microbes have been the dominant life form throughout Earth history."

In addition to Bosak and Newman, the other authors of the paper are Frank Corsetti of USC's department of earth sciences, and Virginia Souza-Egipsy of USC and the Center of Astrobiology in Madrid, Spain.

The paper is titled "Micron-scale porosity as a biosignature in carbonate crusts," and is available online at http://www.gsajournals.org/.

 

 

 

Writer: 
Robert Tindol
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