Structural Biologists Get First Picture of Complete Bacterial Flagellar Motor

PASADENA, Calif.-When it comes to tiny motors, the flagella used by bacteria to get around their microscopic worlds are hard to beat. Composed of several tens of different types of protein, a flagellum (that's the singular) rotates about in much the same way that a rope would spin if mounted in the chuck of an electric drill, but at much higher speeds-about 300 revolutions per second.

Biologists at the California Institute of Technology have now succeeded for the first time in obtaining a three-dimensional image of the complete flagellum assembly using a new technology called electron cryotomography. Reporting in Nature, the scientists show in unprecedented detail both the rotor of the flagellum and the stator, or protein assembly that not only attaches the rotor to the cell wall, but also generates the torque that serves to rotate it.

The accomplishment is a tour de force within the field of structural biology, through which scientists seek to understand how cells work by determining the shapes and configurations of the proteins that make them up. The results could lead to better-designed nanomachines.

"Rotors have been isolated and studied in detail," explains lead author Grant Jensen, an assistant professor of biology at Caltech. "But in the past, researchers have been forced to break the motor into pieces and/or rip it out of the cell before they could observe it in the microscope. It was like trying to understand a car engine by looking through salvaged parts. Here we were able to see the whole motor intact, like an engine still under the hood and attached to the drive train."

In terms of basic science, Jensen says, the motor is intrinsically interesting because it is such a marvelous and complex "nanomachine." But the results of studying it may also one day help engineers, who might want to use its structure to design useful things.

"The process of taking science to practical applications goes from the observation of interesting phenomena, to mechanistic understanding, to exploitation," Jensen says. "Right now, we're somewhere between observation and the beginning of mechanistic understanding of this wonderful motor."

The bacterium used in the study was isolated from the hindguts of termites. Although beneficial to the termite host, the bacterium, belonging to a group of organisms known as spirochetes, is closely related to the causative agents of syphilis, Lyme disease, and several organisms thought to play a role in gum disease. In all these cases, swimming motility is implicated as a possible determinant in disease.

The article is titled "In situ structure of the complete Treponema primitia flagellar motor." It is available as an advanced online publication of Nature at

The other authors are Gavin Murphy, a Caltech graduate student in biochemistry and molecular biophysics, and Jared R. Leadbetter, an associate professor of environmental microbiology at Caltech.

Photo caption: This image shows the three-dimensional reconstruction of the bacterial flagellar motor, as generated by electron cryotomography for the study. The rotor in the center (red) revolves at speeds of up to 300 times per second, driven by the stator assembly (yellow) that is embedded in the cell wall.

Photo by the authors (Gavin Murphy, Jared Leadbetter, and Grant Jensen, Caltech)


Robert Tindol

Moore Foundation Gives $5.6 Million to Caltech for New Center to Study Cell Regulation

PASADENA, Calif.—The Gordon and Betty Moore Foundation has awarded $5.6 million to the California Institute of Technology for the creation of the Center for Integrative Study of Cell Regulation. The goal of the center is to develop new computational methods for understanding how the many genes and proteins that make up individual cells work together to carry out specialized functions of different cell types, including neurons, plant cells, and bacteria.

According to Mary Kennedy, the founding director and Davis Professor of Biology at Caltech, the center will merge Caltech's existing expertise in computation and in cell biology for the pursuit of new knowledge in the biological sciences. "We've reached a turning point where the sequencing of genomes has led to identification of all the genes and proteins of several organisms, and we are now ready to put the pieces together," she explains.

Kennedy says that due to the sheer complexity and volume of information to be handled, application of advanced computational methods and significant computational power is important for further progress. Therefore, the types of problems the center scientists and engineers will work on will include development of algorithms for identifying, locating, and determining the shape and orientation of key proteins in high-resolution cryo-electron microscopic images of cells, and creation of computer programs to simulate complex biochemical signaling pathways in neuronal synapses.

Center personnel will help to develop methods for following the movement of individual cells within a developing embryo in a series of microscopic images and will construct new database architectures for organizing existing data about gene sequences so that comparisons can be made among similar genes in various species.

In short, the center will advance cell biology by introducing new computational methods that haven't previously been widely applied in the life sciences, Kennedy says.

The initial projects will include the modeling of spatial organization, assembly, and function of bacteria and viruses, led by Grant Jensen, an assistant professor of biology at Caltech; the modeling of biochemical mechanisms in brain synapses to better understand the chemistry of learning and memory, led by Kennedy; and the modeling of cell and tissue structure and gene expression during plant development, led by Elliot Meyerowitz, Caltech's division chair of biology.

Marianne Bronner-Fraser, Caltech's Ruddock Professor of Biology, will be involved in the development of a database for uncovering patterns in closely related organisms to better understand the functioning of genes in the evolutionary tree.

The codirector of the center will be Mark Stalzer, who is the executive director of the Center for Advanced Computing Research (CACR) at Caltech. Three or four additional CACR personnel will also be involved in the application of computational methods and programming to problems in integrative cell biology.

During its initial five years of grant funding, the center will help to support the research of about five to ten laboratories in Caltech's Division of Biology and in CACR, which is housed in the Division of Engineering and Applied Science. Other divisions may also be involved as the work progresses.

According to Kennedy, Caltech is in a unique position to create such a center because of its decades-old commitment to close interdisciplinary work among its faculty and research groups, and also because of its longstanding tradition of approaching biological research at the most fundamental levels.

"The future of biology is in the complex level of understanding that must be approached quantitatively, and with the aid of state-of-the-art computers," she says. "So this is a natural change in paradigms."

Established in September 2000, the Gordon and Betty Moore Foundation seeks to develop outcome-based projects that will improve the quality of life for future generations. It has organized the majority of its grant making around large-scale initiatives. It concentrates funding in three program areas: environmental conservation, science, and the San Francisco Bay Area.

Robert Tindol

New Drugs for Smoking Cessation to Be the Target of Grant-Funded Partnership

PASADENA, Calif.—The California Institute of Technology has been awarded a five-year grant for $4.6 million from the National Institute on Drug Abuse to develop a program for discovering medications aimed either at helping people avoid nicotine addiction or at helping smokers to quit. The project will include researchers from the University of Colorado at Boulder and from Targacept, a North Carolina-based biopharmaceutical company whose scientists are leaders in research focused on a class of receptors known as neuronal nicotinic receptors.

Henry Lester, Caltech's Bren Professor of Biology and presently chair of the Caltech faculty, is directing the project, which is called a "National Cooperative Drug Discovery Group in Smoking Cessation." Lester's group will develop new strains of mice, each exaggerating the action of a particular nicotinic receptor subtype. The researchers plan to define the behavior of the mice, and of nerve cells in these mice, as they respond to nicotine and to candidate smoking-cessation drugs.

Lester's group has already established a track record in the study of nicotine addiction. In November 2004, the Caltech and Boulder groups published an article in Science announcing experimental results with "knock-in" mice, whose receptors had been genetically engineered for hypersensitivity to nicotine. The results indicated that specific drug interventions for addressing nicotine addiction were, in principle, very possible to design.

Special mice provide a fruitful way to go about the design of new drugs because an experimental animal designed for hypersensitivity to nicotine is appropriate for tracking nicotine-dependent molecular signals within the nervous system. A goal is to find ways to block one or more of these signals to interfere with the release of dopamine, which has long been associated with pleasure and contentment. Another goal is to interfere with the molecular changes that constitute addiction itself. With the accomplishment of these goals, smoking might never become an irresistible, pleasurable habit.

"I personally believe that nicotine addiction will be among the first addictions to be solved, because we already have so many tools to study it," Lester said in 2004 after the Science paper was published.

In the new research program, the Lester group will provide "target selection" by identifying the most promising strategies for developing drugs. The Boulder group, led by Michael Marks, will conduct discovery and optimization phases by applying sophisticated biochemical measurements to the mice, further describing the response to individual drugs.

Targacept's efforts will be led by Merouane Bencherif. Targacept will identify from its compound portfolio candidate drugs that interact selectively with the applicable nicotinic receptor subtypes. Targacept designs, discovers, and develops novel compounds that act upon various subtypes to promote therapeutic effects and to limit adverse side effects. In addition to the new project in smoking cessation, Targacept's therapeutic focus is on central-nervous-system diseases and disorders such as Alzheimer's disease and other cognitive disorders, along with schizophrenia, pain, depression, and anxiety.

The National Cooperative Drug Discovery Group brings together the complementary talents of these groups to define useful approaches to smoking cessation. Advisors to the group include William Corrigall, who first proved that nicotine is addictive in animals; Allan Collins of Boulder, an expert on the genetics of nicotine and alcohol addiction; and Dennis Dougherty, Caltech's Hoag Professor of Chemistry, who has worked with Lester for years on the chemistry of neuroreceptors.

Although many complex steps occur between primary research and clinical use of a drug, the researchers hope that by studying the biology of nicotinic receptors, the compounds that act on these receptors, and their effect upon stylized animal behaviors that resemble addiction, they will define new principles applicable to smoking cessation and facilitate the development of effective new therapies.

The National Institute on Drug Abuse is part of the National Institutes of Health.


Robert Tindol

Caltech and UC San Diego School of Medicine Create Program to Train Academic Physicians

PASADENA and SAN DIEGO, Calif.—High-school seniors looking for a futuristic way of studying medicine may want to take note. Beginning next year, six newly admitted freshmen at the California Institute of Technology will also be offered early admission to the University of California, San Diego, (UCSD) School of Medicine, pending completion of their Caltech degrees as "medical scholars."

The launch of this new program corresponds with a new report released by the Association of American Medical Colleges (AAMC) advocating stepped-up efforts to educate clinician-researchers who are able to "propel scientific advances into better diagnostics, treatments and preventatives of disease" ("Promoting Translational and Clinical Science: The Critical Role of Medical Schools and Teaching Hospitals," released by the AAMC Task Force II on Clinical Research, can be found online at

According to David Baltimore, president of Caltech, the new program will allow the institute to "tap into an elite pool of students" and to be more directly involved in the training of physicians with especially strong backgrounds in research.

"Many of our top students with interests in biology, bioengineering, biophysics, and chemistry have always intended to apply to medical school once they leave Caltech," said Baltimore. "This joint program with UCSD will allow the two institutions to select an outstanding group of students who are at the top academically and are committed to helping others."

"This partnership with Caltech will help us identify promising individuals with the potential to become leaders and innovators in medicine and life sciences. This will help fill the need for physicians who can not only deliver care, but improve health through basic and clinical research," said Marye Anne Fox, chancellor of UC San Diego.

The first students admitted to the program in the fall of 2007 will be selected through the undergraduate admissions process at Caltech and will be further screened by the UCSD School of Medicine. Typical medical scholars will have been involved in biomedical research and/or clinical endeavors at the high-school level and, like all other students at Caltech and the UCSD School of Medicine, will have excellent grades and test scores.

Once the medical scholars have graduated from Caltech, they will matriculate at the UCSD School of Medicine, provided they have maintained good academic standing. Any Caltech major will be acceptable for matriculation at the medical school.

During the students' undergraduate years at Caltech, UCSD faculty will be involved in programs of special seminars and lectures that will introduce them to a range of subjects that are part of the medical-school experience.

Paul Patterson, the Biaggini Professor of Biological Sciences at Caltech, says the new program will serve two large purposes. "We think it will give us access to the very high-quality pool of biology undergraduates who may currently be going elsewhere because they think Caltech is too difficult or too oriented toward the physical sciences," he said.

"But also, the training will be different from the standard training premeds get at other schools because of the rigorous undergraduate program in the physical sciences and mathematics, and the wide opportunities here for research. So this will be good for medical research as well."

Judith Swain, MD, dean for translational medicine at the UC San Diego School of Medicine, echoes these comments. The program is modeled after UCSD's Medical Scholars Program, which identifies 12 first-year undergraduates at UC San Diego who are guaranteed admission to the UCSD medical school provided they maintain good academic standing and have competitive grades and test scores.

"By getting to these students early and introducing them to the broad variety of careers available to them in medicine and research, we cultivate a strong pool of individuals interested in becoming basic and clinical researchers, innovative clinicians, scholars, and teachers-tomorrow's medical leaders," she said.

"These are the type of people who contribute to our understanding of the pathological and genetic basis of disease and go on to develop new treatments and diagnostic technologies. In addition, having this opportunity to matriculate outstanding students who will have completed Caltech's science and mathematics curriculum will enrich our medical school's student body."

"Our experience at UCSD is that the Medical Scholars Program allows students the opportunity to explore scholarly pursuits without the anxieties so many premedical students have about restricting their curricular and extracurricular activities to those thought to be most appealing to medical-school admissions committees," added Carolyn Kelly, MD, associate dean for admissions and student affairs, UCSD School of Medicine.


Robert Tindol

Study of embryonic sea lampreys provides new insight into the evolution of vertebrates

PASADENA, Calif.—Among the sea beasts commonly displayed at public aquariums is a rather odd-looking fellow known as a lamprey. Possessing a circular mouth that looks like a suction cup with teeth, lampreys have the distinction of being the most primitive of all creatures with backbones.

Now, biologists from the California Institute of Technology have pinned down a key evolutionary relationship that links lampreys with other vertebrates-including humans. Although lampreys and humans shared their last common ancestor some 560 million years ago, it turns out that the SoxE family of genes is involved in facial development of lampreys during neural crest development, just as SoxE is responsible for formation of the human pharynx and parts of the jaw.

In the June 8 issue of Nature, Caltech's Ruddock Professor of Biology Marianne Bronner-Fraser and David McCauley (now at the University of Oklahoma) show that the role of SoxE in the development of the neural crest reveals new insights into the early evolution of vertebrates. Their work focuses on early embryonic development in lampreys and shows that its facial development is similar to that of the much more evolutionarily advanced zebrafish and frog often used in biological experiments.

The reason the findings give new insight into evolutionary biology is that the lamprey is so primitive that it doesn't actually have a jawbone, as do virtually all other vertebrates. Biologists already knew that SoxE genes were responsible for creation of the neural crest-a transient cell population in the early embryo that leads to the formation of structures such as the peripheral nervous system, and bones and cartilage of the skull. But their discovery that SoxE genes are also involved in the development of lamprey head structures extends the knowledge of the evolution of the face a bit farther back.

"We studied lampreys because we are interested in finding out where vertebrates came from," says Bronner-Fraser. "Lampreys are not necessarily the ideal experimental animal, since they breed only once a year for about a month, but they're the most primitive vertebrate on Earth today, and therefore are the closest approximation to our common ancestors of 560 million years ago."

Bronner-Fraser and McCauley performed the study by knocking out one of the SoxE genes in one half of the developing lamprey embryo. As a result, the embryos developed into creatures that were normal on one side, but had abnormalities of the pharynx on the other side.

The results showed that the SoxE disruption is indeed sufficient to interfere with normal neural crest development, which in turn demonstrates that normal neural crest development in lampreys is dependent on normal SoxE expression.

Therefore, the ancestor of lampreys and all other vertebrates had head structures derived from the neural crest. The research also shows that SoxE genes have independent roles in the creation of the mandible and pharynx, and that the neural crest has a crucial role in the proper patterning of the pharynx.

In addition to providing new information about the early evolution of life, the Bronner-Fraser lab's research on the neural crest could lead to eventual treatments of certain congenital defects when the treatment of embryonic problems becomes a reality.

Robert Tindol

Biologists Uncover New Details of How Neural Crest Forms in the Early Embryonic Stages

PASADENA, Calif.—There's a time soon after conception when the stem cells in a tiny area of the embryo called the neural crest are working overtime to build such structures as the dorsal root ganglia, various neurons of the nervous system, and the bones and cartilage of the skull. If things go wrong at this stage, deformities such as cleft palates can occur.

In an article in this week's issue of Nature, a team of biologists from the California Institute of Technology announce that they have determined that neural crest precursors can be identified at surprisingly early stages of development. The work could lead to better understanding of molecular mechanisms in embryonic development that could, in turn, lead to therapeutic interventions when prenatal development goes wrong.

According to Marianne Bronner-Fraser, the Ruddock Professor of Biology at Caltech, the findings provide new information about how stem cells eventually form many and diverse cell types in humans and other vertebrates.

"We've always assumed that the precursor cells that form the neural crest arise at a time when the presumptive brain and spinal cord are first visible," she says. "But our work shows that these cells arise much earlier in development than previously thought, and well before overt signs of the other neural structures.

"We also show that a DNA binding protein called Pax7 is essential for formation of the neural crest, since removal of this protein results in absence of neural crest cells."

The work involves chicken embryos, which are especially amenable to the advanced imaging techniques utilized at Caltech's Biological Imaging Center. The results showed that interfering with the Pax7 protein also interfered with normal neural crest development.

"Because neural crest cells are a type of stem cell able to form cell types as diverse as neurons and pigment cells, understanding the molecular mechanisms underlying their formation may lead to therapeutic means of generating these precursors," Bronner-Fraser explains. "It may also help treat diseases of neural crest derivatives, like melanocytes, that can become cancerous in the form of melanoma."

The work was funded by the NIH and performed at Caltech by Martin Garcia-Castro, a former postdoctoral researcher who is currently an assistant professor at Yale University, and Martin Basch, a former Caltech graduate student who is currently a postdoctoral fellow at the House Ear Institute.

The paper appears in the May 11 issue of Nature. The title of the article is "Specification of the neural crest occurs during gastrulation and requires Pax7."

Robert Tindol

Watson Lecture: Modeling Mental Illness

PASADENA, Calif.--Several landmark discoveries over the past two years have linked the immune system with schizophrenia and also with autism. These findings provide support for a new mouse model of mental illness in which the activation of a pregnant mother's immune system alters the brain development and behavior of her offspring.

In epidemiological studies, researchers have found that viral infection in a pregnant woman during certain critical periods of gestation increases the risk for schizophrenia or autism in her offspring. Moreover, there is new evidence for an altered immune state in the brains of patients with these illnesses.

In modeling this phenomenon in mice, Paul Patterson and his colleagues have found that giving a mother a flu infection midway through her pregnancy leads to striking behavioral abnormalities in her offspring. Activation of the mother's immune system also causes abnormalities in brain development that resemble those seen in patients with schizophrenia and autism. This mouse model therefore allows researchers to study the mechanism through which the mother's immune system alters fetal brain development.

On Wednesday, May 17, Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences at the California Institute of Technology, will discuss this research and how it could someday lead to new ways to treat--and possibly prevent--schizophrenia and autism. His talk, "Can One Make a Mouse Model of Mental Illness, and Why Try?" is the last program of the Winter/Spring 2006 Earnest C. Watson Lecture Series.

The talk will be presented 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

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Aerospace Engineers and Biologists Solve Long-Standing Heart Development Mystery

PASADENA, Calif.—An engineer comparing the human adult heart and the embryo heart might never guess that the former developed from the latter. While the adult heart is a fist-shaped organ with chambers and valves, the embryo heart looks more like tube attached to smaller tubes. Physicians and researchers have assumed for years, in fact, that the embryonic heart pumps through peristaltic movements, much as material flows through the digestive system.

But new results in this week's issue of Science from an international team of biologists and engineers show that the embryonic vertebrate heart tube is indeed a dynamic suction pump. In other words, blood flows by a dynamic suction action (similar to the action of the mature left ventricle) that arises from wave motions in the tube. The findings could lead to new treatments of certain heart diseases that arise from congenital defects.

According to Mory Gharib, the Liepmann Professor of Aeronautics and Bioengineering at the California Institute of Technology, the new results show once and for all that "the embryonic heart doesn't work the way we were taught.

"The morphologies of embryonic and adult hearts look like two different engineers designed them separately," says Gharib, who has worked for years on the mechanical and dynamical nature of the heart. "This study allows you to think about the continuity of the pumping mechanism."

Scott Fraser, the Rosen Professor at Caltech and director of the MRI Center, adds that the study shows the promise of advanced biological imaging techniques for the future of medicine. "The reason this mechanism of pumping has not been noticed in the heart tube is because of the limitations of imaging," he says. "But now we have a device that is 100 times faster than the old microscopes, allowing us to see things that previously would have been a blur. Now we can see the motion of blood and the motions of vascular walls at very high resolutions."

The lead author of the paper is Gharib's graduate student Arian Forouhar. He and the other researchers used confocal microscopes in the Beckman Institute's biological imaging center on campus to do time-lapse photography of embryonic zebrafish. According to Fraser, embryonic zebrafish were chosen because they are essentially transparent, thus allowing for easy viewing, and since they develop completely in only a few days.

The time-lapse photography showed that peristalsis, an action similar to squeezing a tube of toothpaste, was not the pumping mechanism, but rather that valveless pumping known as "hydroelastic impedance pumping" takes place. In this model fewer active cells are required to sustain circulation.

Contraction of a small collection of myocytes, usually situated near the entrance of the heart tube, initiates a series of forward-traveling elastic waves that eventually reflect back after impinging on the end of the heart tube. At a specific range of contraction frequencies, these waves can constructively interact with the preceding reflected waves to generate an efficient dynamic-suction region at the outflow tract of the heart tube.

"Now there is a new paradigm that allows us to reconsider how embryonic cardiac mechanics may lead to anomalies in the adult heart, since impairment of diastolic suction is common in congestive heart-failure patients," says Gharib.

"The heart is one of the only things that makes itself while it's working," Fraser adds. "We often think of the heart as a thing the size of a fist, but it likely began forming its structures when it was a tiny tube with the diameter of a human hair."

"One of the most intriguing features of this model is that only a few contractile cells are necessary to provide mechanical stimuli that may guide later stages of heart development," says Forouhar. According to Gharib, this simplicity in construction will allow us to think of potential biomimicked mechanical counterparts for use in applications where delicate transport of blood, drugs, or other biological fluids are desired.

In addition to Forouhar, Gharib, and Fraser, the authors are Michael Liebling, a postdoctoral scholar in the Beckman Institute's biological imaging center; Anna Hickerson (BS '00; PhD '05) and Abbas Nasiraei Moghaddam, graduate students in bioengineering at Caltech; Huai-Jen Tsai of National Taiwan University's Institute of Molecular and Cellular Biology; Jay Hove of the University of Cincinnati's Genome Research Institute; and Mary Dickinson of the Baylor College of Medicine.

The article is titled "The Embryonic Vertebrate Heart Tube is a Dynamic Suction Pump," and appears in the May 5 issue of Science.

Robert Tindol

Two from Caltech Faculty Elected to the American Academy of Arts and Sciences

PASADENA, Calif.—Two faculty members at the California Institute of Technology are among this year's newly elected fellows of the American Academy of Arts and Sciences. They join 173 other Americans and 20 foreign honorees as the 2006 class of fellows of the prestigious institution that was cofounded in 1780 by John Adams.

This year's new Caltech inductees are Anneila Sargent, the Rosen Professor of Astronomy and director of the Combined Array for Research in Millimeter-Wave Astronomy (CARMA), and Henry Lester, the Bren Professor of Biology. Their election brings the total number of fellows from Caltech to 83.

Sargent and Lester join an illustrious list of fellows, both past and present. Other inductees in the 2006 class include former presidents George H. W. Bush and William Jefferson Clinton; Supreme Court Chief Justice John Roberts; Nobel Prize-winning biochemist and Rockefeller University President Sir Paul Nurse; the chairman and vice chairman of the 9/11 commission, Thomas Kean and Lee Hamilton; actor and director Martin Scorsese; choreographer Meredith Monk; conductor Michael Tilson Thomas; and New York Stock Exchange chairman Marshall Carter. Past fellows have included George Washington, Benjamin Franklin, Ralph Waldo Emerson, Albert Einstein, and Winston Churchill.

Sargent, a native of Scotland, is an authority on star formation. Most recently she has been investigating the way in which stars like the sun are created and evolve to become planetary systems. She uses various radio and submillimeter telescopes to search for and study other potential planetary systems.

Her interests range from the earliest stages of star formation, when dense cores in interstellar clouds collapse to form stars, to the epochs when individual planets may be born. This field has garnered considerable interest within the scientific community, as well as from the news media and the general public, because of the possibility of locating other worlds beyond the solar system.

She is a former president of the American Astronomical Society, incoming chair of the National Research Council's board of physics and astronomy, cochair of the 1996 "Search for Origins" workshop sponsored by the White House Office of Science and Technology Policy, a former chair of NASA's space science advisory committee, and a member of the 2000 National Research Council's survey committee on astronomy and astrophysics.

Her major honors include the 2002 University of Edinburgh Alumnus of the Year award and the 1998 NASA Public Service Medal.

Lester is a New York City native who has been a Caltech faculty member since 1973. His lab is currently involved in several avenues of research, but he is probably best known for his research on the neuroscience of nicotine addiction. A recipient of research funding from the California-based Tobacco-Related Disease Research Program (TRDRP) and the National Institutes of Health, Lester has published numerous papers showing the underlying mechanisms of nicotine addiction.

In 2004, he and collaborators from Caltech and other institutions announced their discovery that activating the receptor known as alpha4 involved in the release of the neurotransmitter dopamine is sufficient for reward behavior, sensitization, and tolerance to repeated doses of nicotine. The discovery was important, experts said, because knowing precisely the cells and cell receptors that are involved could provide useful targets for addiction therapies.

Lester, Caltech chemist Dennis Dougherty, and a group from the University of Cambridge last year announced their success in finding the "switch" part of receptors like those for nicotine and serotonin.

His other current research interests include ion channels, synaptic transmission, light-flash physiology, and signal transduction. Within the past year he has also published papers on the creation of mouse models for epilepsy, tardive dyskinesia, Alzheimer's disease, and Parkinson's disease. The academy is an independent policy research center that focuses on complex and emerging problems such as scientific issues, global security, social policy, the humanities and culture, and education.

The new fellows and foreign honorary members will be formally recognized at the annual induction ceremony on October 7 at the academy's headquarters in Cambridge, Massachusetts.

Robert Tindol
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Benzer Receives $500,000 Albany Medical Center Prize

PASADENA, Calif.--Seymour Benzer, a California Institute of Technology neuroscientist, molecular biologist, and physicist who uncovered genetic links to behavior in fruit flies that today serve as the foundation for the study and treatment of human neurological diseases, has been named the recipient of the $500,000 Albany Medical Center Prize in Medicine and Biomedical Research.

In the 1960s, Benzer and his students demonstrated how mutations in single genes could have a radical effect on behavior in the fruit fly, Drosophila. The fly would later prove to be a model organism for the study of neurological disease, due to the remarkable degree of similarity between the fly and human genomes.

Benzer's seminal discoveries, which ran counter to the prevailing theory that environment was the primary factor in shaping human behavior, profoundly influenced a generation of scientists who, along with Benzer, identified the genetic basis for differences in circadian rhythm, courtship, learning, and memory in fruit flies. Heralded by the scientific community as the "father of neurogenetics," Benzer's pioneering work opened the field to exploration of models for specific neurodegenerative diseases of the human brain such as Alzheimer's, Huntington's chorea, Parkinson's, and amyotrophic lateral sclerosis (Lou Gehrig's disease).

Benzer is the James Griffin Boswell Professor of Neuroscience, Emeritus (Active), at Caltech. An octogenarian whose unconventional circadian rhythm has fueled all-night laboratory research sessions for more than half a century, Benzer is credited with founding the discipline of neurogenetics, defined broadly as the science of how genes control development and function of the nervous system and the brain, and influence behavior. Prior to pioneering this field, Benzer made his mark with monumental discoveries in molecular biology that bridged the gap between DNA and the fine structure of the gene, which helped to pave the way for the Human Genome Project, an effort to map and sequence every one of the three billion letters in the human genome.

In addition to honoring Benzer and his work, this year's prize ceremony paid tribute to Morris "Marty" Silverman, founder of the Albany Medical Center Prize, who died in January 2006 at the age of 93. Silverman founded the Albany Prize in November 2000 with a $50 million gift commitment to Albany Medical Center. A New York City businessman and philanthropist, born in Troy, N.Y., and educated in nearby Albany, Silverman succeeded in realizing his dream to have the prize widely recognized as "America's Nobel."

"This year we honor two outstanding visionaries, Seymour Benzer and Marty Silverman--one a great scientist, the other a world-class philanthropist--each of whom has made an immortal contribution to mankind and to whom the world owes an infinite debt of gratitude," said James J. Barba, chairman of the board, president and chief executive officer of Albany Medical Center, who also chairs the national selection committee for the Albany Medical Center Prize.

The Albany Medical Center Prize is the largest prize in medicine in the United States and worldwide is second only to the Nobel Prize in Physiology and Medicine. The annual prize--announced each spring--was created to encourage and recognize extraordinary and sustained contributions to improving health care and promoting biomedical research with translational benefits applied to improved patient care.

Benzer was selected for the Albany Medical Center Prize for his entire body of scientific work, which spans more than half a century and has incorporated the disciplines of solid-state physics, molecular biology, and neurogenetics. In the 1950s, using mutations in a virus that devours bacteria, Benzer made the seminal discovery that a single gene could be cut and dissected into many parts, which would help lay the groundwork for the explosion of genetic mapping and genetic engineering that now dominate biology.

Albany Medical Center is one of only 125 academic health sciences centers in the nation and the only such health care institution in northeastern New York.


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Greg McGarry
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