Caltech Professor to Explore Abrupt Climate Changes

PASADENA, Calif.—By analyzing stalagmites from caves in Sarawak, which is the Malaysian section of Borneo and the location of one of the world's oldest rain forests, and by studying deep-sea corals from the North Atlantic Ocean, California Institute of Technology researcher Jess Adkins will explore the vital link between the deep ocean, the atmosphere, and abrupt changes in global climates.

The project, "Linking the Atmosphere and the Deep Ocean during Abrupt Climate Changes," is funded by the Comer Science and Educational Foundation.

Because the Sarawak stalagmites and the deep-sea corals are uranium rich and can be dated precisely, and because they both accumulate continuously, uninterrupted by "bioturbation," the biological process that mixes the upper several centimeters of ocean sediments, they provide unique archives of climate history. By utilizing these archives, Adkins and his research group will be able to chart and link major climate variables, and thereby provide critical insight into understanding rapid climate changes that could impact the earth.

Adkins, an assistant professor of geochemistry and global environmental science, joined Caltech in 2000. He received his PhD in 1998 from the Massachusetts Institute of Technology Woods Hole Oceanographic Institute.

The Comer Science and Education Foundation was established to promote education and discovery through scientific exploration.

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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New study describes workings of deep oceanduring the Last Glacial Maximum

Scientists know quite a bit about surface conditions during the Last Glacial Maximum (LGM), a period that peaked about 18,000 years ago, when ice covered significant portions of Canada and northern Europe.

But to really understand the mechanisms involved in climate change, scientists need to have detailed knowledge of the interaction between the ocean and the atmosphere. And until now, a key component of that knowledge has been lacking for the LGM because of limited understanding of the glacial deep ocean.

In a paper published in the November 29 issue of the journal Science, researchers from the California Institute of Technology and Harvard University report the first measurements for the temperature-salinity distribution of the glacial deep ocean. The results show unexpectedly that the basic mechanism of the distribution was different during icy times.

"You can think of the global ocean as a big bathtub, with the densest water at bottom and the lightest at top," explains Jess Adkins, an assistant professor of geochemistry and global environmental science at Caltech and lead author of the paper. Because water that is cold or salty--or both--is dense, it tends to flow downward in a vertical circulation pattern, much like water falling down the sides of the bathtub, until it finds its correct density level. In the ocean today, this circulation mechanism tends to be dominated by the temperature of the water.

In studying chlorine data from four ocean drilling program sites, the researchers found that the glacial deep ocean's circulation was set by the salinity of the water. In addition, a person walking on the ocean bottom from north to south, 18,000 years ago, would have found that the water tended to get saltier as he proceeded (within an acceptable margin of error, both north and south waters were the same temperature). Taking that into account, the water in the north would have been less dense. The exact reverse is true today, with the waters at low southern latitudes being very cold and relatively fresh, while those in the high northern latitudes being warmer and saltier.

Adkins says there is a good explanation for the change. The seawater "equation of state" dictates that the density of water near the freezing point is about two-to-three times more sensitive to changes in salinity relative to changes in temperature, as compared to today's warmer deep waters.

So, the equation demands that the density-layering of the ocean "bathtub" be set by the water's salt content at the last glacial maximum. Temperature is still crucial, in that colder waters are more sensitive to salinity changes than warmer water, but Adkin's results show that the deep water circulation mechanism must have operated in a fundamentally different manner in the past.

"This observation of the deep ocean seems like a strange place to go to study Earth's climate, but this is where you find most of the mass and thermal inertia of the climate system," Adkins says.

The ocean's water temperature enters into the complex mechanism affecting the climate, with water moving about in order for the ocean to equalize its temperature. Too, the water and air interact to further complicate the weather equation.

Thus, the results from the glacial deep ocean shows that the climate in those days was operating in a very different way, Adkins says. "Basically, the purpose of this study is to understand the mechanisms of climate change."

In addition to Adkins, the other authors are Katherine McIntyre, a postdoctoral scholar in geochemistry at Caltech; and Daniel P. Schrag of the Department of Earth and Planetary Sciences at Harvard University.

Contact: Robert Tindol (626) 395-3631

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RT

Rupture of Denali fault responsible for 7.9-magAlaskan earthquake of November 3

Geologists just back from a reconnaissance of the 7.9-magnitude Alaska earthquake of November 3 confirm that rupture of the Denali fault was the principal cause of the quake.

According to Caltech geology professor Kerry Sieh, Central Washington University geological sciences professor Charles Rubin, and Peter Haeussler of the U.S. Geological Survey, investigations over a week-long period revealed three large ruptures with a total length of about 320 kilometers. The principal rupture was a 210-kilometer-long section of the Denali fault, with horizontal shifts of up to nearly 9 meters (26 feet). This places the rupture in the same class as those that produced the San Andreas fault's two historical great earthquakes in 1906 and 1857. These three ruptures are the largest such events in the Western Hemisphere in at least the past 150 years.

Like California's San Andreas, the Denali is a strike-slip fault, which means that the blocks on either side of the fracture move sideways relative to one another. Over millions of years, the cumulative effect of tens of thousands of large shifts has been to move southern Alaska tens of kilometers westward relative to the rest of the state. These shifts have produced a set of large aligned valleys that arch through the middle of the snowy Alaska range, from the Canadian border on the east to the foot of Mount McKinley on the west. Along much of its length the great fracture traverses large glaciers. Surprisingly, the fault broke up through the glaciers, offsetting large crevasses and rocky ridges within the ice.

At the crossing of the Trans-Alaska pipeline, approximately in the center of the 320-kilometer rupture, the horizontal shift was about 4 meters. Fortunately, geological studies of the fault prior to construction led to a special design that would have allowed for shifts greater than this without failure of the pipeline.

The earthquake shook loose thousands of snow avalanches and rock falls in the rugged terrain adjacent to the fault. Although most of these measured only a few tens of meters in dimension, many were much larger. In some places enormous blocks of rock and ice fell onto glaciers and valley floors, skidding a kilometer or more out over ice, stream, and tundra.

The team of investigators included geologists from several organizations, including Caltech's Division of Geological and Planetary Sciences, the U.S. Geological Survey, Central Washington University, and the University of Alaska. The rugged range is traversed by just two highways, and so the scientists used helicopters to access the fault ruptures in the remote and rugged terrain.

Before departing for the field, the geologists had learned from seismologists the basic character of the rupture. Within a day of the quake, Caltech seismologist Chen Ji had determined that the shift along the fault was principally horizontal, but that the initial 20 seconds of the eastward-propagating crack was along a fault with vertical motion. This fault was discovered midweek, near the western end of the principal horizontal shift. Along this 40-kilometer-long fault, a portion of the Alaska range has risen several meters.

Perhaps the most surprising discovery in the field was that the fault rupture propagated only eastward from the epicenter and left the western half of the great fault unbroken. Several members of the team wonder if, in fact, this great earthquake is the first in a series of large events that will eventually include breaks farther west toward Mount McKinley and Denali National Park.

Contact: Robert Tindol (626) 395-3631

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RT

Cellular choreography, not molecular prepattern, creates repeated segments of vertebrate embryo

In a study that combines state-of-the-art biological imaging with gene expression analysis, scientists at the California Institute of Technology have uncovered a fundamental insight into the way embryonic cells and tissue move about to form key structures along the vertebrate axis. The study, which could lead to a better understanding of human development, takes advantage of the accessibility of chick embryos to embryonic manipulation.

The study by Caltech biologists Scott Fraser and Paul Kulesa, appearing in the November 1 issue of the journal Science, centers on segments known as somites, which form along either side of the future spinal cord of an embryo. Somites give rise to mature structures such as ribs, individual vertebrae, and even skin. The key role of somite segmentation in the patterning of the nervous system and the vertebral column has been long known. But the question of precisely how an individual somite buds off from a block of tissue in a pattern that is repeated all along the animal's torso, from head to tail, is poorly understood.

"Developmental biologists have had a difficult time getting a handle on how cell movements and gene expression patterns are coordinated to form complex structures, in this case the segmented units called somites," says Kulesa, a postdoctoral scholar in Fraser's lab and lead author of the paper. "The problems have been due to limitations in obtaining cellular resolution of tissue deep within living vertebrate embryos and difficulty in coordinating the cell movements and tissue shaping in living tissue with gene expression patterns typically obtained at one time point from fixed, non-living tissue."

The new insight of the paper is that the factors that determine the embryo's ultimate form as well as the eventual position of its cells involve a complicated set of motions of the cells themselves. Previous models of embryonic patterning had suggested that there was a molecular prepattern that subdivided the tissues, somewhat like a "paint-by-numbers" piece of art. The study thus shows the action of a more complex coordination between physical forces within the tissue and gene expression patterns that determine where an embryonic cell will go and what type of structure it will help form.

Kulesa and Fraser's study is made possible with a new culture technique combined with confocal time-lapse microscopy, an advanced form of imaging that allows the tissue of a living, developing embryo to be studied in intricate detail at the cellular level. Time-lapse imaging involves, first, labeling the tissue so that it will fluoresce when exposed to laser light, then passing a laser through the tissue, then reconstructing the fluorescent patterns of individual cells to form a three-dimensional microscopic image. The laser scans over the tissue of the developing embryo every minute or so, which allows the researchers to gather the hundreds of images taken during a several-hour run into a time-lapse video.

Using fertilized eggs, the researchers placed an embryo into a specially designed chamber to allow for high-resolution time-lapse imaging, and afterwards performed gene expression analyses on the same embryo. Thus, they were both videotaping cell movements for 6-to-12 hours as well as analyzing the expression of several genes, including EphA4 and c-Meso1, both thought to play a role in determining future somite boundary sites.

The results showed that the straight-line patterns of gene expression, which were thought to correlate with a simple, periodic slicing of the tissue into blocks, did not predict the complex cell movements. Time-lapse imaging showed that a ball-and-socket separation of tissue takes places in a series of six repeatable steps.

"It turns out that a somite pulls apart from the block of tissue, and cells move in anterior and posterior directions near the forming somite boundary," Kulesa says. "This is contrary to many models of somite segmentation which assume that gene expression boundaries that correlate with presumptive somite boundaries allocate cells into a particular block with very little cell movement.

"This study tells us that we have to be careful about assuming that gene expression patterns strictly determine a cell's fate and position."

Kulesa says the next step is to do the work in mouse embryos, which pose considerably more difficult challenges for developmental imaging, but have a tremendous advantage over chick-embryo imaging in attempting to isolate the role of key genes through gene manipulation.

 

 

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Caltech scientists find largest object in solar system since Pluto's discovery

Planetary scientists at the California Institute of Technology have discovered a spherical body in the outskirts of the solar system. The object circles the sun every 288 years, is half the size of Pluto, and is larger than all of the objects in the asteroid belt combined.

The object has been named "Quaoar" (pronounced KWAH-o-ar) after the creation force of the Tongva tribe who were the original inhabitants of the Los Angeles basin, where the Caltech campus is located. Quaoar is located about 4 billion miles from Earth in a region beyond the orbit of Pluto known as the Kuiper belt. This is the region where comets originate and also where planetary scientists have long expected to eventually find larger planet-shaped objects such as Quaoar. The discovery, announced at the meeting of the Division of Planetary Sciences of the American Astronomical Society in Birmingham, Alabama, today, is by far the largest object found so far in that search.

Currently detectable a few degrees northwest of the constellation Scorpio, Quaoar demonstrates beyond a doubt that large bodies can indeed be found in the farthest reaches of the solar system. Further, the discovery provides hope that additional large bodies in the Kuiper belt will be discovered, some as large, or even larger than Pluto. Also, Quaoar and other bodies like it should provide new insights into the primordial materials that formed the solar system some 5 billion years ago.

The discovery further supports the ever-growing opinion that Pluto itself is a Kuiper belt object. According to recent interpretations, Pluto was the first Kuiper belt object to be discovered, long before the age of enhanced digital techniques and charge-coupled (CCD) cameras, because it had been kicked into a Neptune-crossing elliptical orbit eons ago.

"Quaoar definitely hurts the case for Pluto being a planet," says Caltech planetary science associate professor Mike Brown. "If Pluto were discovered today, no one would even consider calling it a planet because it's clearly a Kuiper belt object."

Brown and Chad Trujillo, a postdoctoral researcher, first detected Quaoar on a digital sky image taken on June 4 with Palomar Observatory's 48-inch Oschin Telescope. The researchers looked through archived images taken by a variety of instruments and soon found images taken in the years 1983, 1996, 2000, and 2001. These images not only allowed Brown and Trujillo to establish the distance and orbital inclination of Quaoar, but also to determine that the body is revolving around the sun in a remarkably stable, circular orbit.

"It's probably been in this same orbit for 4 billion years," Brown says.

The discovery of Quaoar is not so much a triumph of advanced optics as of modern digital analysis and a deliberate search methodology. In fact, Quaoar apparently was first photographed in 1982 by then-Caltech astronomer Charlie Kowal in a search for the postulated "Planet X." Kowal unfortunately never found the object on the plate—much less Planet X—but left the image for posterity.

Because the precise location of Quaoar on the old plates is highly predictable, the orbit is thought to be quite circular for a solar system body, and far more circular than that of Pluto. In fact, Pluto is relatively easy to spot—at least if one knows where to look. Because Pluto comes so close to the sun for several years in its 248-year eccentric orbit, the volatile substances in the atmosphere are periodically heated, thereby increasing the body's reflectance, or albedo, to such a degree that it is bright enough to be seen even in small amateur telescopes.

Quaoar, on the other hand, never approaches the sun in its circular orbit, which means that the volatile gases never are excited enough to kick up a highly reflective atmosphere. As is the case for other bodies of similar rock-and-ice composition, Quaoar's surface has been bathed by faint ultraviolet radiation from the sun over the eons, and this radiation has slowly caused the organic materials on the body's surface to turn into a dark tar-like substance.

As a result, Quaoar's albedo is about 10 percent, just a bit higher than that of the moon. By contrast, Pluto's albedo is 60 percent.

As for spin rate, the researchers know that Quaoar is rotating because of slight variations in reflectance in the six weeks they've observed the body. But they're still collecting data to determine the precise rate. They will also probably be able to figure out whether the spin axis is tilted relative to the ecliptical plane.

Inclination is about 7.9 percent, which means that the plane of Quaoar's orbit is tilted by 7.9 degrees from the relatively flat orbital plane in which all the planets except Pluto are to be found. Pluto's orbital inclination is about 17 degrees, which presumably resulted from whatever gravitational interference originally thrust it into an elliptical orbit.

Quaoar's orbital inclination of 7.9 degrees is not particularly surprising, Brown says, because the Kuiper belt is turning out to be wider than originally expected. The Kuiper belt can be thought of as a band extending around the sky, superimposed on the path of the sun. Brown and Trujillo's research, in effect, is to take repeated exposures of a several-degree swath of this band and then use digital equipment to check and see if any tiny point of light has moved relative to the stellar background.

Brown and Trujillo are currently using about 10 to 20 percent of the available time on the 48-inch Oschin Telescope, which was used to obtain both the Palomar Sky Survey and the more recent Palomar Digital Sky Survey. The latter was completed just last year, thus freeing up the Oschin Telescope to be refitted by the Jet Propulsion Laboratory for a new mission to search for near-Earth asteroids. About 80 percent of the telescope time is now designated for the asteroid survey, leaving the remainder for scientific studies like Brown and Trujillo's.

Since the discovery, the researchers have also employed other telescopes to study and characterize Quaoar, including the Hubble Space Telescope (related news release available at link below) and the Keck Observatory on Mauna Kea, Hawaii. Information derived from these studies will provide new insights into the precise composition of Quaoar and may answer questions about whether the body has a tenuous atmosphere.

But the good news for the serious amateur astronomer is that he or she doesn't necessarily need a space telescope or 10-meter reflector to get a faint image of Quaoar. Armed with precise coordinates and a 16-inch telescope fitted with a CCD camera—the kind advertised in magazines such as Sky and Telescope and Astronomy—an amateur should be able to obtain images on successive nights that will show a faint dot of light in slightly different positions.

As for Brown and Trujillo, the two are continuing their search for other large Kuiper-belt bodies. Some, in fact, may be even larger than Quaoar.

"Right now, I'd say they get as big as Pluto," says Brown.

 

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Caltech researchers devisenew microdevice for fluid analysis

Researchers at the California Institute of Technology announced today a new paradigm for large-scale integration of microfluidic devices. Using new techniques, they built chips with as many as 6,000 microvalves and up to 1,000 tiny individual chambers.

The technology is being commercialized by Fluidigm in San Francisco, which is using multi-layer soft lithography (MSL) techniques to create microfluidic chips to run the smallest-volume polymerase chain reactions documented—20,000 parallel reactions at volumes of 100 picoliters.

In a paper to appear in the journal Science, Caltech associate professor of applied physics and physics Stephen Quake and his colleagues describe the research on picoliter-scale chambers. Quake's team describes the 1,000 individually addressable chambers, and also demonstrates on a separate device with more than 2,000 microvalves, that two different reagents can be separately loaded to perform distinct assays in two subnanoliter chambers and then recover the contents of a single chamber.

According to Quake, who cofounded Fluidigm, the devices should have many new scientific, commercial, and biomedical applications. "We now have the tools in hand to design complex microfluidic systems and, through switchable isolation, recover contents from a single chamber for further investigation."

"Together, these advancements speak to the power of MSL technology to achieve large-scale integration and the ability to make a commercial impact in microfluidics," said Gajus Worthington, President and CEO of Fluidigm. "PCR is the cornerstone of genomics applications. Fluidigm's microprocessor, coupled with the ability to recover results from the chip, offers the greatest level of miniaturization and integration of any platform," added Worthington.

Fluidigm hopes to leverage these advancements as it pursues genomics and proteomics applications. Fluidigm has already shipped a prototype product for protein crystallization that transforms decades-old methodologies to a chip-based format, vastly reducing sample input requirements and improving cost and labor by orders of magnitude.

Contact: Robert Tindol (626) 395-3631 t

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Humans and chimps have 95 percent DNA compatibility, not 98.5 percent, research shows

Genetic studies for decades have estimated that humans and chimpanzees possess genomes that are about 98.5 percent similar. In other words, of the three billion base pairs along the DNA helix, nearly 99 of every 100 would be exactly identical.

However, new work by one of the co-developers of the method used to analyze genetic similarities between species says the figure should be revised downward to 95 percent.

Roy Britten, a biologist at the California Institute of Technology, reports in the current issue of the journal Proceedings of the National Academy of Sciences that the large amount of sequencing that has been done in recent years on both the human and chimp genomes—and improvements in the techniques themselves—allow for the issue to be revisited. In the article, he describes the method he used, which involved writing a special computer program to compare nearly 780,000 base pairs of the human genome with a similar number from the chimp genome.

To describe exactly what Britten did, it is helpful to explain the old method as it was originally used to determine genetic similarities between two species. Called hybridization, the method involved collecting tiny snips of the DNA helix from the chromosomes of the two species to be studied, then breaking the ladder-like helixes apart into strands. Strands from one species would be radioactively labeled, and then the two strands recombined.

The helix at this point would contain one strand from each species, and from there it was a fairly straightforward matter to "melt" the strands to infer the number of good base pairs. The lower the melting temperature, the less compatibility between the two species because of the lower energy required to break the bonds.

In the case of chimps and humans, numerous studies through the years have shown that there is an incidence of 1.2 to 1.76 percent base substitutions. This means that these are areas along the helix where the bases (adenine, thymine, guanine, and cytosine) do not correspond and hence do not form a bond at that point.

The problem with the old studies is that the methods did not recognize differences due to events of insertion and deletion that result in parts of the DNA being absent from the strands of one or the other species. These are different from the aforementioned substitutions. Such differences, called "indels," are readily recognized by comparing sequences, if one looks beyond the missing regions for the next regions that do match.

To accomplish the more complete survey, Britten wrote a Fortran program that did custom comparisons of strands of human and chimp DNA available from GenBank. With nearly 780,000 suitable base pairs available to him, Britten was able to better infer where the mismatches would actually be seen if an extremely long strand could be studied. Thus, the computer technique allowed Britten to look at several long strands of DNA with 780,000 potential base pairings.

As expected, he found a base substitution rate of about 1.4 percent—well in keeping with earlier reported results—but also an incidence of 3.9 percent divergence attributable to the presence of indels. Thus, he came up with the revised figure of 5 percent.

As for the implications, Britten says the new work should help biologists with future work on precisely how species branch off from each other, and why. "The basic question you would like to answer is what makes the chimp different from humans—what were the basic changes in the genome that mattered.

"A large number of these 5 percent of variations are relatively unimportant. But what matters, according to everyone's idea, is regulation of the genes, which is controlled by the genes that are actually expressed. So to address this issue, you first have to know how different the genomes are, and second, where the differences are located.

The article is available from PNAS by contacting Jill Locantore, the public information officer, at jlocantore@nas.edu, or by calling 202-334-1310.

Contact: Robert Tindol (626) 395-3631

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RT

Caltech-MIT Team Finds 35% Improvementin Florida's Voting Technology

PASADENA, Calif. — If one measures election success by equipment performance alone, Florida's push to get new voting equipment on-line for the 2002 election appears to have paid off.

Compared with the performance of equipment in past Florida state primary elections, the new technologies for casting and counting ballots look like clear improvements according to experts at the California Institute of Technology and the Massachusetts Institute of Technology.

Researchers from the Caltech/MIT Voting Technology Project calculated the rate of residual votes (ballots on which no votes or too many votes were recorded) for the largest counties in Florida for the 2002 Democratic Gubernatorial Primary and for the last three Gubernatorial General Elections in Florida (1990, 1994, and 1998). These counties are Brevard, Broward, Duval, Hillsborough, Miami-Dade, Palm Beach, and Pinellas.

The residual vote rate, it appears, has been substantially reduced as a result of the election reform efforts of the past year. On average, 2.0 percent of Democratic voters recorded no vote for governor in these seven counties. In past elections, the average has been 3.1 percent. This is a 35 percent improvement in performance.

The largest apparent improvements came in Brevard and Duval counties, which switched from punch cards to optically scanned paper ballots. The remaining counties purchased new touch screen or Direct Recording Electronic (DRE) machines. All of the counties show some improvement in their capacity to record and count votes.

Residual Vote Rates for Governor in the 7 Largest Florida Counties

County

2002 Democratic Primary

Voting Equipment

Residual Vote Rate

   

2002

1998

Ave.

1998

General

1994 General

1990 General

Brevard

1.0%

Scanner

Punch

4.2%

2.6%

4.5%

5.4%

Broward

2.0

DRE

Punch

2.6

2.7

1.9

3.3

Dade

3.0

DRE

Punch

3.2

4.0

2.7

3.2

Duval

2.2

Scanner

Punch

3.4

3.1

2.5

4.5

Hillsborough

1.6

DRE

Punch

2.3

2.7

1.9

N/A

Palm Beach

2.3

DRE

Punch

3.1

3.7

2.3

3.3

Pinellas

1.9

DRE

Punch

2.2

2.3

1.9

2.3

Total

2.0

   

3.1

     

"These results are very encouraging," said Stephen Ansolabehere, a professor at the Massachusetts Institute of Technology and co-director of the project. "Florida made a major effort to upgrade its technology and, in the primary, the machines used showed clear gains over the technologies in past elections."

Professor Charles Stewart, another MIT professor working on the Voting Technology Project, cautions that "the success of an election cannot be measured solely in terms of equipment performance. Current events in Florida also illustrate how better technology is just a first step in improving the functioning of democracy." Stewart said, "Most of the problems reported by journalists covering the 2002 Primary Elections in Florida did not concern equipment malfunctions, but problems encountered preparing for election day, such as training poll workers."

R. Michael Alvarez, co-director of the Voting Technology Project and professor of political science at the California Institute of Technology, said "As counties and states across the country, especially here in California, plan out similar changes, we are learning important lessons about how to make such important changes in voting technologies."

"The one distressing thing, though, are the reports from Florida that polling place workers had difficulties getting some of the new voting machines up and running on election day in Florida, and that as a result, some voters might have been turned away from the polling places. These reports reinforce our calls for more polling place workers and better training of polling place workers, as they provide a critical role in making sure that all votes are counted," Alvarez said.

MIT's Stewart adds "The fact that the congressional election reform bill is currently stalled in a House-Senate conference committee hasn't helped matters any."

The Caltech/MIT Voting Technology Project is a non-partisan research project, formed to study election systems following the 2000 presidential election and sponsored by the Carnegie Corporation. More information and copies of reports are available at www.vote.caltech.edu.

### MEDIA CONTACT: Jill Perry Caltech Media Relations Director (626) 395-3226 jperry@caltech.edu

Sarah Wright or Ken Campbell MIT News Office 617 253-2700 shwright@mit.edu

Visit the Caltech media relations web site: http://pr.caltech.edu/media

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Caltech to be part of $15.5-million federal grantto understand how living cells communicate

A California Institute of Technology research group that specializes in distributed information systems has been named one of the collaborators in the Alpha Project, a $15.5-million, five-year program for advancing knowledge of how living cells respond to information and communicate with each other.

The Caltech research group is headed by Jehoshua Bruck, who is the Gordon and Betty Moore Professor of Computation and Neural Systems and Electrical Engineering at Caltech. Bruck will receive more than $1 million of the $15.5 million Alpha Project grant, which has been awarded by the National Institutes of Health's National Human Genome Research Institute to the Molecular Sciences Institute, which will oversee the coordinated effort. The Alpha Project will also involve research groups from MIT, UC Berkeley, and Pacific Northwest National Laboratory.

The aim of the Alpha Project is to "enable broad understanding of cellular and organismic behavior and work towards making predictive models of biological systems that will serve to radically improve researchers' abilities to understand biology by providing them with advanced methods and tools to probe important biological questions." Bruck's part of the work will be in the analysis, abstraction, and modeling of cellular signal transduction.

"Basically, signal transduction is the regulatory process that controls how a cell communicates with other cells, or senses things in its environment," Bruck explains. "We'll study this chemical signal processing in baker's yeast cells, which are very similar to human cells in the way they carry out signal transduction. Hence, yeast will serve as our 'model system.'"

The entire Alpha Project will be focused on studying the pheromone signal pathway in baker's yeast. This biological pathway involves a relatively small number of about 25 genes, so it is hoped that thoroughly understanding the system will provide new insights on how cells respond to stimuli and communicate in humans.

Bruck has interacted for the last two years with the Molecular Sciences Institute on creating computer algorithms for simulating biological regulatory systems, which is similar to the work he will do on the Alpha Project. "We are not planning to conduct experiments with yeast in my lab," he says. "Our part will be to model the whole process, and create simulations to try to predict the behavior of the biological system.

"Also, we plan to learn from biology about new principles in circuits for computation and communications, because at present, we simply don't know how to build artificial systems that compute, communicate, and evolve like biological cells."

Success for the overall mission of the Alpha Project will mean advances that could lead to new ways of dealing with diseases such as cancer and diabetes.

"At the least, we'll definitely understand this communication pathway in cells," Bruck says of the biological goals. "And if we are able to understand the mechanisms in a way that leads to advances in curing diseases, and this information can also be applied to engineering systems, it would be even better."

Much of Bruck's research focuses on distributed information systems, which he defines as "a system comprising more than a single entity, such as a group of computing devices that interact by a wired or wireless communication network."

The Alpha Project will be the flagship project at the Molecular Sciences Institute's new Center for Genomic Experimentation and Computation.

The Molecular Sciences Institute, headquartered in Berkeley, is an independent, nonprofit research laboratory that combines genomic experimentation with computer modeling. The mission of the institute is to predict the behavior of cells and organisms in response to defined genetic and environmental changes. Progress toward this goal will significantly increase our understanding of biological systems and help catalyze radical changes in how diseases are understood and treated.

In addition to the new $15.5-million funding from the National Human Genome Research Institute, the Molecular Science Institute is supported by other federal grants and funds provided by foundations and corporations. The institute's Web address is www.molsci.org.

Contact: Robert Tindol (626) 395-3631

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RT

Brain oscillations compress odor representations as signals pass through olfactory networks

Most natural smells are complex blends of many individual chemicals. Freshly ground coffee, for example, contains about 300 individual volatile components. A typical perfume also contains tens of ingredients, although the recipes are tightly locked in secret vaults.

The percepts that such complex blends evoke in us are, however, astonishingly singular: ground coffee smells like coffee, not like a hopeless mess of hundreds of ingredients; Gio or Allure also have unique signatures (often associated with other memories). This contrast between a physical object's complexity and the uniqueness of how we perceive it is the expression of what brains do best: "bind" features together into highly recognizable patterns.

This is as true of smell as it is for the other senses: a person can immediately recognize his mother's face or voice. How this useful and effortless compression of information is accomplished by the brain is one of the deep mysteries of neuroscience. In addition, understanding the mechanisms of compression would help in the design of computerized pattern recognizers (e.g., face recognition devices), a very difficult task with many important applications.

This issue is the subject of new research from neurobiologist Gilles Laurent and his team in the California Institute of Technology's computation and neural systems program. In a paper appearing in the July 19 issue of the journal Science, the Laurent team reports that the complicated wiring in grasshoppers between the antennal lobe (the insect analog of the olfactory bulb in humans) and the mushroom body (the insect analog of the olfactory cortex) is arranged and functions in such a way that highly detailed information in the former is bound or compressed for future memory use in the latter.

To better explain the details of their discovery, it's probably best to first explain the organs of smell in grasshoppers. The first area associated with smell are the receptor cells that are the front line of cells coming into contact with the chemical elements of a smell. Information from the receptor neurons converge in the antenna lobe, which, in grasshoppers, comprises about 1,000 individual neurons. The signal then goes to the mushroom body, which comprises about 50,000 neurons.

By intricately wiring glass, silicon, and platinum wire electrode arrays into the brains of hundreds of grasshoppers to record activity from their neurons, then exposing the insects to a variety of smells, the Laurent team has demonstrated some of the fine details of this wiring and its consequences for odor encoding.

When a specific odor is detected by a grasshopper, the antennal lobe neurons, wired to the peripheral detector array, start a complicated "dance" that engages about half of its 1,000 neurons. Each individual odor evokes a different dance or spatio-temporal pattern that involves partially overlapping subsets of neurons activated at varying times. Hence, determining from these patterns the odor's identity is a very difficult task; it requires that an observer decode the details of the dance, identify the correlations between the activities of all the neurons, and put all this back together into a coherent whole. Said differently, the informative value of any antennal lobe neuron in isolation is close to zero: valuable information comes only from deciphering the message carried by the population.

Population decoding is precisely what is done by the downstream neurons (called Kenyon cells, in the mushroom body). Those neurons, using a complicated combination of wiring, biophysical properties, brain oscillations, and loops of inhibition, manage to compress the information carried by many antennal lobe neurons into highly specific and sparse signals. Thus, individual Kenyon cells are silent most of the time and produce a signal only in response to very specific odors. The signals from these neurons, when given out, are thus highly informative, Laurent says.

"If you observe Kenyon cell No. 2,976 and see that it produced one single pulse, you can be pretty confident that the animal has just detected a certain odor mixture and not another," he explains. Each Kenyon cell thus has a very limited, but highly specific repertoire of "preferred stimuli."

At the same time, this compression eliminates much of the information about the individual chemical elements that make up an odor. "Knowing that Kenyon cell No. 2,976 fired may tell me that the (grasshopper) just smelled a cherry blend, but it tells me nothing about the chemical composition of that smell."

This may explain why these individual elements cannot be perceived; the encoding and decoding of an odor as a whole (cherry or Gio) is done at a cost: detail is lost. The advantage, however, is that the storage and retrieval of this odor's representation has become very simple, fast, and manageable: Each odor, however complex, is now represented by very few, highly specific neurons. Because the mushroom body has many neurons (and our olfactory cortex has even more), a huge number of such memories can be stored.

"There are many reasons to think that odor perception may work in similar ways in vertebrates, including humans," Laurent says, explaining that the antennal lobe in insects, including flies, is very similar to the mammalian olfactory bulb, except that it possesses many fewer cells; and that the mushroom body is likewise similar to the human olfactory cortex.

"In the case of humans as well as animals, the brain is not doing analytical chemistry by pulling out individual components," he says. "Instead, you have a very good memory for odors, however complex, even though you lose information about details. After all, throwing away information is one of the most important things that brains do, but it must be done carefully.

"In olfaction as well as in vision and the other senses, the brain must represent and memorize a huge number of complicated patterns. One should expect that evolution has found an optimal way of solving this task. Our work provides the beginnings of a solution, although whether it applies to other senses remains to be seen."

In addition to Laurent, the other authors of the study, all members of Caltech's Division of Biology, are Javier Perez-Orive, Ofer Mazor, Glenn C. Turner, Stijn Cassenaer, and Rachel I. Wilson.

The paper is available online at http://www.sciencemag.org.

Contact: Robert Tindol (626) 395-3631

Writer: 
RT

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