Caltech, UC Berkeley to Investigate How Brain Activity Controls Complex Behavior

PASADENA, Calif.—A new $4.4-million grant from the National Science Foundation will allow researchers at the California Institute of Technology and the University of California, Berkeley, to develop techniques to turn brain cells on and off in animals as they go about their daily activities, allowing the scientists to understand the details of how brain activity leads to complex behaviors.

According to principal investigator Michael Dickinson, the Zarem Professor of Bioengineering at Caltech, the five-year program is aimed at solving one of the remaining great challenges facing biologists—understanding the mechanistic basis of complex behavior. The work will focus on fruit flies, which are a powerful model system understood extremely well at the genetic level.

"New approaches available in molecular genetics can now be applied to manipulate individual brain cells in an attempt to understand how brains control behavior," says Dickinson. "We'll also use recent advances in engineering to create new devices to observe and measure behavioral changes in a manner as rigorous as those available to detect genetic differences."

The work will involve experiments in which the activity of specific cells in the nervous systems of fruit flies can be controlled using light. "The idea is to bioengineer ion channels that can be opened and closed with light flashes," Dickinson explains. "By controlling these genetically engineered ion channels, we can directly manipulate the electrical impulses that nervous systems use to sense and process information.

"This approach will allow us to study the function of specific cells and circuits in intact animals," Dickinson adds. Coinvestigator Ehud Isacoff of the University of California, Berkeley, will create these ion channels.

A fly might be engineered, for example, to begin flying or walking when pulsed with light of a certain wavelength. But this would be a means to a scientific goal and not the ultimate goal itself.

"This is one way of tapping into the fly and making cells do what we want them to do in order to test specific hypotheses about brain structure and behavior," Dickinson says. David Anderson, a coprincipal investigator and the Sperry Professor of Biology at Caltech, will work to place the light-controlled ion channels within as many unique cells in the flies' nervous systems as possible.

Prior work on the cellular basis of behavior has focused on how networks of brain cells may control simple behaviors such as swimming, flying, and feeding. The new work will probe these behaviors at a deeper level, attempting to figure out how nervous systems-and possibly even individual nervous-system cells-regulate simpler motor actions over time and space to generate more complex behaviors.

A central goal of the research will be to determine how a nervous system uses sensory data to process changes in a complex set of behaviors. Thus, the scientists will not only study the details of how the flies' sensory-based locomotion (walking and flying) works, but how their locomotion is related to crucial survival activities such as looking for food, seeking mates, laying eggs, searching for shelter, and getting out of harm's way.

"We will begin with the assumption that an animal's own natural behavior is the best context in which to interpret how its nervous system is built," Dickinson says. "The first step is to gather quantitative behavioral information concerning the external and internal cues that cause flies to change or modulate what they are doing.

"The next step is to gain experimental access to the specific cells that control these behavioral transitions, so we will develop genetically engineered flies that allow us to control the neurons that send information from the sensory areas of the brain to the circuits that generate and control movement. We will also study how gene expression controls and alters brain wiring.

"Collectively, this may help unravel one of the central questions in neuroscience: how brains regulate behavioral transitions."

Additional information on this and related grants is at

Robert Tindol

Caltech Gets $18 Million from NHGRI to Map Vertebrate Development

PASADENA, Calif.—The National Human Genome Research Institute (NHGRI), a component of the National Institutes of Health (NIH), has awarded an $18-million grant for creation of a Center of Excellence in Genomic Science at the California Institute of Technology.

According to Marianne Bronner-Fraser, the Ruddock Professor of Biology at Caltech and principal investigator of the five-year program, the goal will be to image and mutate every developmentally important gene in vertebrates—that is, animals with backbones.

The work will be performed together with co-investigators Sean Megason and Scott Fraser from the Division of Biology, and Niles Pierce, an assistant professor of applied and computational mathematics and bioengineering.

"We will combine real-time analysis of gene expression on a genome-wide scale with the ability to mutate genes of interest," Bronner-Fraser says.

Initially, the research team will focus on the zebrafish, which is ideal for this type of work because of its transparent embryo and its rapid development.

"Our goal is to create the 'digital fish,'" Megason says. "This will be a computer model of the genetic orchestra that transforms an egg into an embryo."

"There will be an enormous payoff in new information about how development works at the genomic level," Bronner-Fraser adds.

The researchers will use new "in toto" imaging and genetic tagging tools invented by Megason and Fraser and new molecular detection methods being developed in the Pierce lab to analyze gene expression and function in the developing embryos. They will digitize this molecular data on a genomic scale by capturing thousands of time-lapse videos as the animals develop.

Once the approach is worked out on zebrafish, it will also be applied to the Japanese quail to make a "digital bird," because bird embryos develop in a fashion very similar to human embryos.

The Caltech grant is part of a $54-million grant portfolio awarded by the NHGRI for funding interdisciplinary work in genomic research. The NHGRI is best known for spearheading the Human Genome Project, which completely mapped the genetic blueprint of humans.

Now that the sequence of the genome for humans and many other species has been determined, the challenge ahead is to figure out how the genome functions during development and disease which is the goal of the CEGS (Center for Excellence in Genomic Science) program.

"The CEGS program is vital to our efforts to apply innovative genomic tools and technologies to the study of human biology," said NHGRI Director Francis S. Collins. "By fostering collaboration among researchers from many different disciplines, NHGRI aims to encourage innovation and build a powerful new framework for exploring human health and disease."

Robert Tindol

Meyerowitz and Lange Awarded Balzan Prize

PASADENA, Calif.- California Institute of Technology faculty Andrew Lange and Elliot Meyerowitz have been named Balzan Prizewinners for 2006 by the International Balzan Foundation. Lange, Goldberger Professor of Physics, will share his award for observational astronomy and astrophysics with Paolo de Bernardis of Università di Roma La Sapienza in Italy "...for their contributions to cosmology, in particular the "BOOMERanG" Antarctic balloon experiment."

Lange and Italian team leader de Bernardis led the international team that developed BOOMERanG (Balloon Observations of Millimetric Extragalactic Radiation and Geophysics), a balloon-borne telescope capable of obtaining images of the universe in its embyronic state, long before the first stars formed. The images obtained in 1998, during a 10-day circumnavigation of Antarctica, revealed that the geometry of the universe is flat, and provided compelling evidence that 95 percent of the universe consists of exotic forms of matter and energy that remain largely a mystery.

Meyerowitz, Beadle Professor of Biology and biology division chair, will share his award for plant molecular genetics with Chris R. Somerville of Stanford University "...for their joint efforts in establishing Arabidopsis as a model organism for plant molecular genetics. This has far-reaching implications for plant science, both on a fundamental level and in potential applications."

Meyerowitz's primary research interest is the genes that control the formation of flowers, how altering these genes will affect flower development; and using computational models to study how plants grow. His laboratory has identified mutations that cause petal cells to develop into stamens instead, and another mutation that causes these same embryonic petals to become sepals. They and their collaborators have also produced computer models that faithfully reproduce the cellular behavior of meristems, the growing tips of shoots.

The winners named will be presented with their Balzan (pronounced bal-ZAHN) Prizes personally by the president of the Italian Republic, Giorgio Napolitano, during an award ceremony November 24 at the Accademia Nazionale dei Lincei, in the Palazzo Corsini in Rome. Each prize is worth one million Swiss francs, about $810,000 US. Because both Lange and Meyerowitz share their prizes with one other person, they will each receive half of the total, or about $405,000 US. Half of the prize money is awarded directly to the prizewinners in recognition of their outstanding scholarly work and they are asked to spend the other half on research projects carried out by young scholars or scientists in their respective fields.

The recipients were chosen by the General Prize Committee, a body chaired by Ambassador Sergio Romano and composed of 20 members representing European cultural institutions, from the candidates nominated by universities, academies, and cultural institutions throughout the world.

Unlike other international forms of recognition, the Balzan Prizes are awarded for different subjects each year, which are chosen annually by the Balzan Foundation. Two prizes are awarded in the humanities (literature, the moral sciences, and the arts) and two in the sciences (medicine and the physical, mathematical, and natural sciences). By rotating subjects, it is possible for the foundation to give preference to new or emerging areas of research, and to sustain important fields of study that may have been previously overlooked.

Additional recipients this year are Ludwig Finscher of the University of Heidelberg, Germany, for history of Western music since 1600, and Quentin Skinner of University of Cambridge, UK, for political thought: history and theory.

In 2007, Balzan Prizes will be awarded in European literature (1000-1500), international law since 1945, innate immunity, and nanoscience. The Prize for Humanity, Peace, and Brotherhood among Peoples will also be awarded next year; past winners include Mother Teresa and the International Committee of the Red Cross.

The International Balzan Foundation was founded in 1961 to promote the worthy causes of culture, the sciences and humanities, and peace and brotherhood in the world. The main concern of the foundation is to award the Balzan Prizes, which are given annually to individuals who have earned international distinction in their field, regardless of their nationality, race, or creed. At intervals of not less than three years, the Balzan Foundation also awards the Prize for Humanity, Peace, and Brotherhood among Peoples, which is worth two million Swiss francs. The Balzan Foundation operates on an international level through its two offices, which are legally distinct bodies: its Milan, Italy, headquarters is concerned with awarding the prizes, while the estate of Eugenio Balzan, which funds the Balzan Prizes, is managed from Zurich, Switzerland.

For details, see the Balzan Foundation website: ### Contact: Jill Perry (626) 395-3226 Visit the Caltech Media Relations website at

Exclude from News Hub: 

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

Visit the Caltech Media Relations website at:



Subscribe to RSS - BBE