Researchers Improve Understanding of Mechanical Properties of Carbon Nanotubes With New Computer Simulation

PASADENA, Calif.—Carbon nanotubes are tiny garden-hose-like hollow tubes that have considerable promise for future applications such as nano-sized plumbing and nanolithography, and for the creation of numerous tiny devices such as mass sensors and actuators. Such applications require improved understanding of the mechanical properties of carbon nanotubes. Previous studies pointed out that carbon nanotubes behave like macroscopic elastic hoses similar to garden hoses made of rubber.

Now, researchers at the California Institute of Technology have discovered through computer simulations that the bending of carbon nanotubes occurs differently from that of their macroscopic counterparts in significant ways. Rather than buckling immediately and squashing the hollow inner channel, the results show, the cross-section can be gradually flattened—a finding that could lead to applications in controlling the flow of fluids through real carbon nanotubes. The results are published in the current issue of the journal Physical Review Letters.

According to Konstantinos Giapis, an associate professor of chemical engineering at Caltech and lead author of the paper, the size of nanotubes that he and postdoctoral scholar Oleksandr Kutana used for the simulation are between two and seven nanometers—or less than one-ten-thousandth the diameter of a human hair. Previous studies had focused on smaller nanotubes.

When the slightly larger nanotubes are "bent" sufficiently in the simulation, Giapis explains, the walls meet when the two sides are brought close enough together, and an atomic attraction known as the van der Waals force causes the atoms of each side of the wall to stick together. This effectively clamps off the nanotube, stopping any flow of material within it until the tube is re-straightened.

"The results show that there is an intermediate regime where you can adjust the nanotube cross-section to your liking," Giapis says. "This intermediate bending regime is important for nanofluidics."

Unlike a garden hose, however, nanotubes are tiny enough to feel forces that are inconsequential in the macroscopic world. Whereas the van der Waals force is much too weak to cause the walls of a garden hose to stick together, the force should be sufficient at the microscopic level to act as a "glue" to hold the walls of nanotubes together even after the load has been partially removed.

The end result, Giapis explains, is a new understanding of how it may be possible to control microflow in the emerging world of nanotechnology. "The initial study was to understand how nanotubes bend and how their bending differs from that of macroscopic objects, but there are also practical applications.

"For future microfluidic devices, you're going to need valves," he says. These devices could include everything from pharmaceutical-delivery systems to nano-inkjet printers.

The article is available on-line at http://link.aps.org/abstract/PRL/v97/e245501.

 

Writer: 
RT
Writer: 
Exclude from News Hub: 
No

Chemist Nelson J. Leonard Dies

PASADENA, Calif.—Nelson J. Leonard, one of the most important chemists of the 20th century, died Monday, October 9, at his home in Pasadena, California. He was 90.

Leonard was born on September 1, 1916, in Newark, New Jersey, and attended Lehigh University in Bethlehem, Pennsylvania, before moving to Oxford University as a Rhodes Scholar. The beginning of World War II in September 1939 forced Leonard's return to the United States.

Upon his return, Leonard continued his graduate education in chemistry, concluding with a Ph.D. in 1942 from Columbia University. His research, which focused on structure establishment and partial synthesis of alstonine, a naturally occurring antimalarial compound, was performed under the direction of Robert C. Elderfield.

A postdoctoral research assistantship brought Leonard to the University of Illinois Urbana-Champaign, where he worked with professor Roger Adams on Senecio alkaloids. Teaching duties were added to his research responsibilities in 1943, and his students eventually included U.S. Navy and U.S. Army units passing through the University of Illinois. He joined a team led by professors Charles C. Price III and Harold R. Snyder engaged in research to forward the synthesis and production of the important antimalarial drug chloroquine in time for its use in the Pacific theater.

At the end of the war, during 1945 and 1946, Leonard served as a scientific consultant and special investigator in the Field Intelligence Agency Technical (FIAT), U.S. Army and U.S. Department of Commerce, European Theater. He then returned to the University of Illinois and remained on the teaching staff until his retirement in 1986. Beginning in 1992, he held the position of faculty associate in chemistry at the California Institute of Technology.

From 1943 until 1955, Leonard combined his academic work in chemistry with a flourishing musical career, as he performed as a bass-baritone soloist in choral works with the Chicago, Cleveland, and St. Louis symphony orchestras. When in 1955 Leonard was elected to membership in the National Academy of Sciences, he felt that if his peers had chosen to recognize him as a chemist, then he had "better do something about it." The heavy professional demands of chemistry would take precedence, and there would be no more singing performances.

In collaboration with professor Folke Skoog, a plant physiologist at the University of Wisconsin, Leonard carried out extensive investigations of organic compounds that initiate plant, flower, and tree growth from tissue culture, technology that is central to horticultural and agricultural development. His techniques for derivatization of nucleosides, nucleotides, and coenzymes, and to prepare fluorescent probes, placed him among the most often quoted scientists.

Over the course of his career, he published more than 400 scientific papers and trained more than 200 Ph.D. students and postdoctoral scholars. In addition to his early election to membership in the National Academy of Sciences, Leonard was a fellow of the American Academy of Arts and Sciences and a member of the American Philosophical Society. His research distinctions included the prestigious Roger Adams Award in Organic Chemistry (1981) and Arthur C. Cope Scholar Award (1995) of the American Chemical Society.

Chemistry was not the only part of Leonard's life that was interrupted by the war. Through family connections, he had met and fallen in love with Louise Cornelie Vermey of the Netherlands. They were engaged, but were not able to see each other again until the end of the war in 1945, and were unable to arrange for her journey to the United States and marriage until 1947. She died in 1987.

Leonard is survived by his wife, Peggy Phelps, of Pasadena; his daughter, Marcia, of Maplewood, New Jersey; his sons Kenneth, of Agoura Hills, James, of Olympia, Washington, and David, of Seattle, Washington; and seven grandchildren.

A memorial service is planned for 3 p.m. Monday, November 13, at All Saints Church, 132 North Euclid Avenue, Pasadena. Memorial donations should be made to the Nelson J. Leonard Fund at the Pasadena Symphony.

Writer: 
Robert Tindol
Writer: 

Caltech Chemist Jacqueline Barton Receives Gibbs Medal from American Chemical Society

PASADENA, Calif.—Jacqueline Barton, the Arthur and Marian Hanisch Memorial Professor and professor of chemistry at the California Institute of Technology, has been named the 2006 recipient of the Willard Gibbs Award. The honor was bestowed on Barton at a special award dinner hosted by the Chicago section of the American Chemical Society on May 12 in Des Plaines, Illinois.

Barton becomes the second woman to receive the honor in its 95-year history, the first having been Marie Curie in 1921. Barton and her husband, Peter Dervan (the Bren Professor of Chemistry at Caltech), also become the first husband and wife to have won the Gibbs Award.

Established in 1911, the Gibbs Award is presented annually to a researcher who pioneers new avenues of investigation in chemistry. Barton is cited for her "major impact on the understanding of the molecular chemistry of DNA and its relevance to the development of a variety of diseases and inherited abnormalities.

"Her work is elegant, vitally important work that has been widely recognized for its novelty and significance," the citation continues. "Professor Barton pioneered the application of transition metal complexes as tools to probe recognition and reactions of double helical DNA. This work provides a new approach to the study of DNA structure and dynamics. She has carried out important studies to examine the transport of electric charge through DNA, establishing reactions by which DNA can be damaged from a distance as well as how lesions in DNA can be repaired, locally or at distant sites on the DNA helix. Her work also provides the basis for sensitive diagnostic sensors for DNA."

A New York native, Barton earned her bachelor's degree, summa cum laude, at Barnard College in 1974 and her doctorate in inorganic chemistry at Columbia University in 1978. After several years on the faculty at Columbia, she joined the Caltech faculty in 1989.

She is the recipient of numerous awards, including a MacArthur Foundation Fellowship in 1991, the 1985 Alan T. Waterman Award of the National Science Foundation, which recognizes an outstanding young science or engineering researcher, and the 1988 American Chemical Society Award in Pure Chemistry. She was elected a fellow of the American Academy of Arts and Sciences in 1991, fellow of the American Philosophical Society in 2000, and in 2002 Barton was elected to the National Academy of Sciences.

Other American Chemical Society awards include the 1987 Eli Lilly Award in Biological Chemistry, the 1992 Garvan Medal, the 1997 Nichols Medal, and the 2003 Breslow Award. She has also received the Columbia University Medal of Excellence in 1992, the Mayor of New York's Award in Science and Technology in 1988, the Paul Karrer Gold Medal (University of Zurich) in 1996, and the Weizmann Woman & Science Award in 1998. She has received several honorary degrees, including last year a Doctor of Science from Yale University.

Writer: 
Robert Tindol
Writer: 
Exclude from News Hub: 
Yes

Caltech Researchers Create New Proteins by Recombining the Pieces of Existing Proteins

PASADENA, Calif.—An ongoing challenge in biochemistry is getting a handle on protein folding-that is, the way that DNA sequences determine the unique structure and functions of proteins, which then act as "biology's workhorses." Gaining mastery over the construction of proteins will someday lead to breakthroughs in medicine and pharmaceuticals.

One method for studying the determinants of a protein's structure and function is to analyze numerous proteins with similar structure and function-a protein family-as a group. By studying families of natural proteins, researchers can tease out many of the fundamental interactions responsible for a given property.

A team of chemical engineers, chemists, and biochemists at the California Institute of Technology have now managed to create a large number of proteins that are very different in sequence yet retain similar structures. The scientists use computational tools to analyze protein structures and pinpoint locations at which they can break them apart and then reassemble them, like Lego pieces. Each new construction is a protein with new functions and new potential enzyme actions.

Reporting in the April 10 issue of the Public Library of Science Biology, Caltech graduate student Christopher Otey and his colleagues show that they have successfully taken three proteins from nature, broken them each into eight pieces, and successfully reconstructed the pieces to form many new proteins. According to Otey, the potential number of new proteins from just three proteins is three raised to the eighth power, or 6,561, assuming that each protein is divided into eight segments. "The result is an artificial protein family," Otey explains. "In this single experiment, we've been able to make about 3,000 new proteins."

About half of the 6,561 proteins are viable, having an average of about 72 sequence changes. "The benefit is that you can use the new proteins and new sequence information to learn new things about the original proteins," Otey adds. "For example, if a certain protein function depends on one amino acid that never changes, then the protein apparently must have that particular amino acid."

The proteins the team has been using are called cytochromes P450, which play critical roles in drug metabolism, hormone synthesis, and the biodegradation of many chemicals. Using computational techniques, the researchers predict how to break up this roughly 460-amino-acid protein into individual blocks of about 60 to 70 amino acids.

Otey says that this is an important result when considering the old-fashioned way of obtaining protein sequences. Whereas, over the past 40 years, researchers have fully determined 4,500 natural P450 sequences, the Caltech team required only a few months to create 3,000 additional new sequences.

"Our goal in the lab is to be able to create a bunch of proteins very quickly," Otey says, "but the overall benefit is an understanding of what makes a protein do what it does and potentially the production of new pharmaceuticals, new antibiotics, and such.

"During evolution, nature conserves protein structure, which we do with the computational tools, while changing protein sequence which can lead to proteins with new functions," he says. "And new functions can ultimately result in new treatments."

In addition to Otey, the other authors of the paper are Frances Arnold (the corresponding author), who is Dickinson Professor of Chemical Engineering and Biochemistry at Caltech, and Otey's supervising professor; Marco Landwehr, a postdoctoral scholar in biochemistry; Jeffrey B. Endelman, a recently graduated Caltech graduate student in bioengineering; Jesse Bloom, a graduate student in chemistry; and Kaori Hiraga, a Caltech postdoctoral scholar who is now at the New York State Department of Health.

The title of the article is "Structure-Guided Recombination Creates an Artificial Family of Cytochromes P450."

 

Writer: 
Robert Tindol
Writer: 
Exclude from News Hub: 
No

Watson Lecture: Revolutionary Medicine

PASADENA, Calif.- Imagine taking a medicine that is not only ideally suited for treating your particular ailment but also perfectly designed for YOU and your own unique genetic makeup.

Scientists are making great strides toward the creation of this new generation of personalized pharmaceuticals. On January 18, William A. Goddard III will discuss the progress that has been made and where it might lead in his talk "The Coming Revolution in Pharmaceuticals." Goddard is the Charles and Mary Ferkel Professor of Chemistry, Materials Science, and Applied Physics and director of the Materials and Process Simulation Center at the California Institute of Technology.

The talk, the final program of the 2005-06 Earnest C. Watson Lecture Series, will take place at 8 p.m. in Beckman Auditorium, 332 S. Michigan Avenue south of Del Mar Boulevard, on the Caltech campus in Pasadena. Seating is available on a free, no-ticket-required, first-come, first-served basis. Caltech has offered the Watson Lecture Series since 1922, when it was conceived by the late Caltech physicist Earnest Watson as a way to explain science to the local community.

For more information, call 1(888) 2CALTECH (1-888-222-5832) or (626) 395-4652. ###

Contact: Kathy Svitil (626) 395-8022 ksvitil@caltech.edu

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

Writer: 
KS
Tags: 
Writer: 

Caltech Researchers Achieve First Electrowetting of Carbon Nanotubes

PASADENA, Calif.—If you can imagine the straw in your soda can being a million times smaller and made of carbon, you pretty much have a mental picture of a carbon nanotube. Scientists have been making them at will for years, but have never gotten the nanotubes to suck up liquid metal to form tiny wires. In fact, conventional wisdom and hundreds of refereed papers say that such is not even possible.

Now, with the aid of an 1875 study of mercury's electrical properties, researchers from the California Institute of Technology have succeeded in forcing liquid mercury into carbon nanotubes. Their technique could have important applications, including nanolithography, the production of nanowires with unique quantum properties, nano-sized plumbing for the transport of extremely small fluid quantities, and electronic circuitry many times smaller than the smallest in existence today.

Reporting in the December 2 issue of the journal Science, Caltech assistant professor of chemistry Patrick Collier and associate professor of chemical engineering Konstantinos Giapis describe their success in electrowetting carbon nanotubes. By "electrowetting" they mean that the voltage applied to a nanotube immersed in mercury causes the liquid metal to rise into the nanotube by capillary action and cling to the surface of its inner wall.

Besides its potential for fundamental research and commercial applications, Giapis says that the result is an opportunity to set the record straight. "We have found that when measuring the properties of carbon nanotubes in contact with liquid metals, researchers need to take into account that the application of a voltage can result in electrically activated wetting of the nanotube.

"Ever since carbon nanotubes were discovered in 1991, people have envisioned using them as molds to make nanowires or as nanochannels for flowing liquids. The hope was to have the nanotubes act like molecular straws," says Giapis.

However, researchers never got liquid metal to flow into the straws, and eventually dismissed the possibility that metal could even do so because of surface tension. Mercury was considered totally unpromising because, as anyone knows who has played with liquid mercury in chemistry class, a glob will roll around a desktop without wetting anything it touches.

"The consensus was that the surface tension of metals was just too high to wet the walls of the nanotubes," adds Collier, the co-lead author of the paper. This is not to say that researchers have never been able to force anything into a nanotube: in fact, they have, albeit by using more complex and less controllable ways that have always led to the formation of discontinuous wires.

Collier and Giapis enter the picture because they had been experimenting with coating nanotubes with an insulator in order to create tiny probes for future medical and industrial applications. In attaching nanotubes to gold-coated atomic force microscope tips to form nanoprobes, they discovered that the setup provided a novel way of making liquid mercury rise in the tubes by capillary action.

Casting far beyond the nanotube research papers of the last decade, the researchers found an 1875 study by Nobel Prize-winning physicist Gabriel Lippmann that described in detail how the surface tension of mercury is altered by the application of an electrical potential. Lippmann's 1875 paper provided the starting point for Collier and Giapis to begin their electrowetting experiments.

After mercury entered the nanotubes with the application of a voltage, the researchers further discovered that the mercury rapidly escaped from the nanotubes immediately after the voltage was turned off. "This effect made it very difficult to provide hard proof that electrowetting occurred," Collier said. In the end, persistence and hard work paid off as the results in the Science paper demonstrate.

Giapis and Collier think that they will be able to drive various other metals into the nanotubes by employing the process at higher temperature. They hope to be able to freeze the metal nanowires in the nanotubes so that they remain intact when the voltage is turned off.

"We can pump mercury at this point, but it's possible that you could also pump nonmetallic liquids," Giapis says. "So we now have a way of pumping fluids controllably that could lead to nanofluidic devices. We envision making nano-inkjet printers that will use metal ink to print text and circuitry with nanometer precision. These devices could be scaled up to operate in a massively parallel manner. "

The paper is titled "Electrowetting in Carbon Nanotubes." In addition to Collier and Giapis, the other authors are Jinyu Chen, a postdoctoral scholar in chemistry, and Aleksandr Kutana, a postdoctoral scholar in chemical engineering.

Writer: 
Robert Tindol
Writer: 
Exclude from News Hub: 
No

Researchers uncover new details about how signals are transmitted in the brain

PASADENA, Calif.—An international team of scientists has announced a new breakthrough in understanding the molecular details of how signals move around in the human brain. The work is basic research, but could help pharmacologists design new drugs for treating a host of neurological disorders, as well as drugs for reducing alcohol and nicotine craving.

Reporting in the November 11 issue of the journal Nature, researchers from the California Institute of Technology and the University of Cambridge explain how they have learned to force a protein known as the 5-HT3 receptor to change its function by chemically changing the shape of one of the amino acids from which it is built. Using a technique developed at Caltech known as "unnatural amino mutagenesis," the researchers altered a proline amino acid in the 5-HT3 protein in order to modulate the receptor's ion channel. This gave the researchers control of the "switch" that is involved in neuron signaling.

According to Dennis Dougherty, lead author of the paper and the Hoag Professor of Chemistry at Caltech, the new research solves a 50-year-old mystery of how a neuroreceptor is changed by a chemical signal. Scientists have long known that signaling in the brain is a chemical process, in which a chemical substance known as a neurotransmitter is released into the synapse of a nerve and binds to a neuroreceptor, which is a protein that is found in the surface membranes of neurons. The action of the neurotransmitter changes the neuroreceptor in such a way that a signal is transmitted, but the precise nature of the structural change was unknown until now.

"The key is that we've identified the switch that has to get thrown when the neuroreceptor sends a signal," Dougherty says. "This switch is a proline."

The 5-HT3 receptor is one of a group of molecular structures in the brain cells that are known as Cys-loop receptors, which are associated with Parkinson's disease, schizophrenia, and learning and attention deficit disorders, as well as alcoholism and nicotine addiction. For treatments of some of these conditions, pharmacologists already custom-design drugs that have a general effect on the Cys-loop receptors. But the hope is that better design at the molecular level will lead to much better treatments that address more precisely the underlying signaling problems.

Dougherty says the work required the collaboration of organic chemists, molecular biologists, electrophysiologists and computer modelers. His Caltech group worked closely with the research group of Caltech biologist Henry Lester, and with the group at Cambridge headed by Sarah Lummis, to establish how proline changes its structure to open an ion channel and launch a neuron signal.

"This is the most precise model of receptor signaling yet developed, and it provides valuable insights into the nature of neuroreceptors and the drugs that modulate them," Dougherty says.

"The promise for pharmacology is that precise control of the signaling could lead to new ways of dealing with receptors that are malfunctioning," says Lester, Caltech's Bren Professor of Biology. "The fundamental understanding of how this all works is of value to people who want to manipulate the signaling."

The 5-HT3 receptor is also involved in the enjoyment people derive from drinking alcohol. If the 5-HT3 receptors are blocked, then alcoholics no longer get as much pleasure from drinking. Therefore, better control of the signaling mechanism could lead to more potent drug interventions for alcoholics. The nicotine receptors are also related, so progress could also lead to better ways of reducing the craving for nicotine.

In addition to Dougherty, Lester, and Lummis, the other authors of the paper are Caltech graduate students Darren Beene (now graduated) and Lori Lee, and Cambridge researcher William Broadhurst.

The research is supported by the National Institute of Neurological Disorders and Stroke.

Writer: 
Robert Tindol
Writer: 

Caltech Chemist Robert Grubbs Wins Nobel Prize

PASADENA, Calif.--Robert Grubbs, an organic chemist whose work on catalysis has led to a wide variety of applications in medicine and industry, has won the 2005 Nobel Prize in chemistry. The announcement was made this morning by the Royal Swedish Academy of Sciences in Stockholm.

Grubbs and this year's other two winners were cited specifically "for the development of the metathesis method in organic synthesis." Metathesis is an organic reaction in which chemists selectively strip out certain atoms in a compound and replace them with atoms that were previously part of another compound. The end result is a custom-built molecule that has specialized properties that can lead to better drugs for the treatment of disease, or better electrical conducting properties for specialized plastics, for example.

In particular, Grubbs has worked on olefin metathesis. Prior to Grubbs's work, metathesis was poorly understood and of limited value to scientists. Grubbs developed powerful new catalysts for metathesis that enabled custom synthesis of valuable molecules, such as pharmaceuticals and new polymers with novel materials properties.

According to the Nobel citation, metathesis has already led to industrial and pharmaceutical methods that are more efficient and less wasteful, simpler, and more environmentally friendly. "This represents a great step forward for 'green chemistry,' reducing potentially hazardous waste through smarter production," the Royal Swedish Academy announced.

"Metathesis is an example of how important basic science has been applied for the benefit of man, society, and the environment," the citation continued.

Grubbs is currently spending a month at the University of Canterbury in Christchurch, New Zealand, as an Erskine Fellow. In an e-mail message, he singled out his students and collaborators and said that he was especially pleased that the Nobel committee had chosen to recognize the research that had taken place at Caltech.

"I'm excited for all the outstanding students and postdoctoral fellows who have contributed to this work over the years," Grubbs wrote.

Grubbs added that he has been swamped with calls since the announcement was made earlier today, and that his son--a physician currently serving a residency at the USC Medical School--has been swamped with calls as well.

"Sometime when I'm more rested and I'm available in person, I'll be happy to sit down and discuss the work this award represents," he wrote.

Grubbs' award was an especially welcomed going-away present for Caltech president David Baltimore, who just Monday announced his pending retirement. Baltimore, himself a Nobel laureate, said he was pleased that the Nobel committee had recognized a Caltech researcher whose work had so direct an impact on biomedicine.

"Bob's work shows that basic chemical research continues to have importance to pharmaceuticals and industry, and it also shows that the sometimes highly esoteric work young people do in the lab is a huge contribution to society," said Baltimore. "I congratulate Bob on joining Caltech's growing list of Nobel laureates, and I envy his young students for the elation they're feeling today."

Grubbs is a native of Kentucky who earned his bachelor's and master's degrees at the University of Florida. After completing his doctorate in chemistry at Columbia University, he spent a year at Stanford University as a postdoctoral fellow, and then joined the Michigan State University faculty in 1969. He came to Caltech in 1978 with full tenure as a professor, and has been the Victor and Elizabeth Atkins Professor of Chemistry since 1990.

Grubbs has been a member of the National Academy of Sciences since 1989, and was the 2000 recipient of the Benjamin Franklin Medal.

Today's award brings to 32 the total number of prizes won by 31 Caltech faculty and alumni through the years (Linus Pauling won awards in both chemistry and peace).

Writer: 
RT

Scientists Uncover Rules that Govern the Rate of Protein Evolution

PASADENA, Calif.--Humans and insects and pond scum-and all other living things on Earth-are constantly evolving. The tiny proteins these living things are built from are also evolving, accumulating mutations mostly one at a time over billions of years. But for reasons that hitherto have been a mystery, some proteins evolve quickly, while others take their sweet time-even when they reside in the same organism.

Now, a team of researchers at the California Institute of Technology, applying novel data-mining methods to the now-completed sequence of the yeast genome, have uncovered a surprising reason why different proteins evolve at different rates.

Reporting in the September 19 edition of the journal Proceedings of the National Academy of Sciences (PNAS), lead author Allan Drummond and his coauthors from Caltech and the Keck Graduate Institute show that the evolution of protein is governed by their ability to tolerate mistakes during their production. This finding disputes the longstanding assumption that functionally important proteins evolve slowly, while less-important proteins evolve more quickly.

"The reason proteins evolve at different rates has been a mystery for decades in biology," Drummond explains. But with the recent flood of sequenced genomes and inventories of all the pieces and parts making up cells, the mystery deepened. Researchers discovered that the more of a protein that was produced, the slower it evolved, a trend that applies to all living things. But the reason for this trend remained obscure, despite many attempts to explain it.

Biologists have long known that the production machinery that translates the genetic code into proteins is sloppy. So much so, in fact, that on average about one in five proteins in yeast is mistranslated, the equivalent of translating the Spanish word "Adios" as "Goofbye." The more copies of a protein produced, the more potential errors. And mistakes can be costly: some translation errors turn proteins into useless junk that can even be harmful (like miscopying a digit in an important phone number), while other errors can be tolerated. So the more protein copies per cell, the more potential harm-unless those abundant proteins themselves can evolve to tolerate more errors.

"That was the 'Aha!'" says Drummond. "We knew from our experiments with manipulating proteins in the lab that some had special properties that allowed them to tolerate more changes than other proteins. They were more robust." So, what if proteins could become robust to translation errors? That would mean fewer harmful errors, and thus a more fit organism.

To test predictions of this hypothesis, the team turned to the lowly baker's yeast, a simple one-celled organism that likes to suck up the nutrients in bread dough, and then expels gas to give baked bread its fluffy texture. Baker's yeast is not only a simple organism, it is also extraordinarily well understood. Just as biologists have now sequenced the human genome, they have also sequenced the yeast genome. Moreover, the numbers of every type of protein in the yeast cell have been painstakingly measured.

For example, there's a protein in the yeast cell called PMA1 that acts as a transformer, converting stored energy into more useful forms. Since nothing living can do without energy, this is a very fundamental and important component of the yeast cell. And every yeast cell churns out about 1.26 million individual PMA1 molecules, making it the second-most abundant cellular protein.

The old assumption was that PMA1 changed slowly because its energy-transforming function was so fundamental to survival. But the Caltech team's new evidence suggests that the sheer number of PMA1 molecules produced is the reason that the protein doesn't evolve very quickly.

"The key insight is that natural selection targets the junk proteins, not the functional proteins," says Drummond. "If translation errors turned 5 percent of the PMA1 proteins in a yeast cell into junk, those junk proteins would be more abundant than 97 percent of all the other proteins in the cell. That's a huge amount of toxic waste to dispose of."

So instead, Darwinian evolution favors yeast cells with a version of PMA1 that continues to function despite errors, producing less junk. That version of PMA1 evolves slowly because the slightest changes destroy its crucial ability to withstand errors.

Consider two competing computer factories. Both make the same number of mistakes on their assembly lines, but one company's computers are designed such that the inevitable mistakes result in computers that still work, while with the other company's design, one mistake and the computer must be tossed on the recycling heap. In the cutthroat marketplace, the former company, with lower costs and higher output, will quickly outcompete the latter.

Likewise, viewing yeast cells as miniature factories, the yeast whose most-abundant proteins are least likely to be destroyed by production mistakes will outcompete its less-efficient rivals. The more optimized those high-abundance proteins are--the more rigid the specifications that make them so error-resistant-the slower they evolve. Hence, high abundance means slow evolution.

The team is now exploring other predictions of this surprising hypothesis, such as what specific chemical changes allow proteins to resist translation errors. "It's the tip of the iceberg," Drummond says.

Drummond is a graduate student in Caltech's interdisciplinary Computation and Neural Systems program. The other authors of the paper include his two advisors: Frances Arnold, the Dickinson Professor of Chemical Engineering and Biochemistry at Caltech, and Chris Adami, an expert in population genetics who is now at the Keck Graduate Institute in Claremont, California. The other authors are Jesse D. Bloom, a graduate student in chemistry at Caltech; and Claus Wilke, a former postdoctoral researcher of Adami's who has recently joined the University of Texas at Austin as an assistant professor.

The title of the PNAS paper is "Why highly expressed proteins evolve slowly."

 

Writer: 
Robert Tindol
Writer: 
Exclude from News Hub: 
No

Caltech, MIT Chemists Look for Better Waysto Use Chemical Bonds to Store Solar Energy

PASADENA, Calif.-With gasoline prices hovering at $3 per gallon, probably few Americans need convincing that another energy crisis is imminent. But what precisely is to be done about our future energy needs is still a puzzle. There's talk about a "hydrogen economy," but hydrogen itself poses some formidable challenges.

The key challenge is, of course, how to make the hydrogen in the first place. The best and cheapest methods currently available involve burning coal or natural gas, which means more greenhouse gases and more pollution. Adopting the cheapest method by using natural gas would merely result in replacing our dependence on foreign oil with a dependence on foreign gas.

"Clearly, one clean way to get hydrogen is by splitting water with sunlight," says Harry Gray, who is the Beckman Professor of Chemistry at the California Institute of Technology.

Gray is involved with several other Caltech and MIT chemists in a research program they call "Powering the Planet." The broadest goal of the project is to "pursue efficient, economical ways to store solar energy in the form of chemical bonds," according to the National Science Foundation (NSF). With a new seed grant from the NSF and the possibility for additional funding after the initial three-year period, the Caltech group says they now have the wherewithal to try out some novel ideas to produce energy cheaply and cleanly.

"Presently, this country spends more money in 10 minutes at the gas pump than it puts into a year of solar-energy research," says Nathan S. Lewis, the Argyros Professor and professor of chemistry. "But the sun provides more energy to the planet in an hour than all the fossil energy consumed worldwide in a year."

The reason that Gray and Lewis advocate the use of solar energy is that no other renewable resource has enough practical potential to provide the world with the energy that it needs. But the sun sets every night, and so use of solar energy on a large scale will necessarily require storing the energy for use upon society's demand, day or night, summer or winter, rain or shine.

As for non-renewable resources, nuclear power plants would do the job, but 10,000 new ones would have to be built. In other words, one new nuclear plant would have to come on-line every other day somewhere in the world for the next 50 years.

The devices used in a simple experiment in the high school chemistry lab to make hydrogen by electrolysis are not currently the cheapest ones to use for mass production. In fact, the tabletop device that breaks water into hydrogen and oxygen is perfectly clean (in other words, no carbon emissions), but it requires a platinum catalyst. And platinum has been selling all year for more than $800 per ounce.

The solution? Find something cheaper than platinum to act as a catalyst. There are other problems, but this is one that the Caltech group is starting to address. In a research article now in press, Associate Professor of Chemistry Jonas Peters and his colleagues demonstrate a way that cobalt can be used for catalysis of hydrogen formation from water.

"This is a good first example for us," says Peters. "A key goal is to try to replace the current state-of-the-art platinum catalyst, which is extremely expensive, with something like cobalt, or even better, iron or nickel. We have to find a way to cheaply make solar-derived fuel if we are to ever really enable widespread use of solar energy as society's main power source."

"It's also a good example because it shows that the NSF grant will get us working together," adds Gray. "This and other research results will involve the joint use of students and postdocs, rather than individual groups going it alone."

In addition to the lab work, the Caltech chemists also have plans to involve other entities outside campus--both for practical and educational reasons. One proposal is to fit out a school so that it will run entirely on solar energy. The initial conversion would likely be done with existing solar panels, but the facility would also serve to provide the researchers with a fairly large-scale "lab" where they can test out new ideas.

"We'd build it so that we could troubleshoot solar converters we're working on," explains Gray.

The ultimate lab goal is to have a "dream machine with no wires in it," Gray says. "We visualize a solar machine with boundary layers, where water comes in, hydrogen goes out one side, and oxygen goes out the other."

Such a machine will require a lot of work and a number of innovations and breakthroughs, but Lewis says the future of the planet depends on moving away from fossil fuels.

"If somebody doesn't figure this out, and fast, we're toast, both literally and practically, due to a growing dependence on foreign oil combined with the increasing projections of global warming."

The NSF grant was formally announced August 11 as a means of funding a new group of chemical bonding centers that will allow research teams to pursue problems in a manner "that's flexible, tolerant of risk, and open to thinking far outside the box." The initial funding to the Caltech and MIT group for the "Powering the Planet" initiative is $1.5 million for three years, with the possibility of $2 to $3 million per year thereafter if the work of the center appears promising.

In addition to Gray, Lewis, and Peters, the other Caltech personnel include Jay Winkler and Bruce Brunschwig, both chemists at Caltech's Beckman Institute. The two faculty members from MIT involved in the initiative are Dan Nocera and Kit Cummins.

Jonas Peters's paper will appear in an upcoming issue of the journal Chemical Communications. In addition to Peters and Lewis, the other authors are Brunschwig, Xile Hu, a postdoctoral researcher in chemistry at Caltech, and Brandi Cossairt, a Caltech undergraduate.

 

Writer: 
Robert Tindol
Writer: 

Pages

Subscribe to RSS - CCE