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 www.aamc.org/promotingclinicalscience)

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.

 

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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.

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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."

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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.

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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.

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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.

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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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Contact: Jill Perry
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Greg McGarry
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McDonnell Foundation Grant Will Be Used to Study Neurons Involved in Snap Decisions

PASADENA, Calif.-Where do you get your "gut feelings," that intuition that leads you to distrust someone who appears trustworthy? It could be your Von Economo brain cells in action, and a neurobiologist at the California Institute of Technology intends to find out for sure.

John Allman, the Hixon Professor of Neurobiology, has received a $1.8 million grant from the James S. McDonnell Foundation to study the Von Economo neuron. The funding will allow Allman and his colleagues to perform a wide variety of research on the specialized neurons. The work could lead to new insights into the nature and treatment of various psychiatric disorders.

According to Allman, the Von Economo neurons (or VENs) are large bipolar cells located in the anterior cingulate and fronto-insular cortex. Also referred to as spindle neurons because of their shape, the neurons have been the focus of intense attention by Allman and his team for several years.

"We think that the VENs may have an important role in intuition," Allman says. "By intuition, we mean a form of cognition in which many variables are rapidly evaluated in parallel and compressed into a single dimension for fast decision-making." It is essential for making fast decisions in complex, rapidly changing social contexts.

"We experience the intuitive process at the visceral level," Allman explains. "Intuitive decision-making enables us to react quickly in situations that involve a high degree of uncertainty, which commonly involve social interactions."

In fact, the term "gut reaction" is not accidental, Allman says, because the mechanism may share some wiring with the controlling of the digestive system. One possibility is that the very primitive system originally may have been helpful in keeping animals away from poisonous plants. A rapid reaction, thus, may have evolved so that an animal would know instantly to spit out a noxious berry or risk being poisoned. Allman believes that this system for regulating the consumption of nutritious foods and rejecting those that are toxic was the basis for the neural circuitry governing complex social feelings such as love and hate, empathy and guilt.

Allman says the work is important because VENs may be particularly vulnerable to dysfunction in certain cases in which early development is disturbed. Related brain structures are known to be associated with obsessive-compulsive disorder, psychopathy, fronto-temporal lobe dementia, autism, Asperger's syndrome, and maybe even schizophrenia.

The researchers will use the grant money to work on several related questions, including how the VENs arise during infant development, whether the gut indeed sends direct signals to the VENs, how the VENs in humans compare to those of apes, and whether the VENs are somehow abnormal in the brains of autistic patients.

The James S. McDonnell Foundation grant that Allman has received is formally titled the 21st Century Science Initiative in Bridging Brain, Mind, and Behavior-Collaborative Award.

Founded in 1950 by aerospace pioneer James S. McDonnell, the foundation was established to "improve the quality of life," and does so by contributing to the generation of new knowledge through its support of research and scholarship.

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Contact: Jill Perry (626) 395-3226 jperry@caltech.edu

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Caltech Receives $2.3 Million for Stem Cell Research

PASADENA, Calif.- The California Institute of Technology has been awarded $2.3 million from the California Institute for Regenerative Medicine to support 10 postdoctoral scholars in the Caltech Stem Cell Biology Training Program.

The grant is one of 16 that were awarded by CIRM to non-profit institutions in California. The grants total $12.1 million and are intended to train the next generation of stem cell researchers. They are the first grants awarded by the California stem cell agency.

"This is an exhilarating day for the scientists, patients and the millions of Californians who support stem cell research," said Robert Klein, chairman of the Independent Citizens' Oversight Committee, the agency's governing board. "CIRM was created to fund science in the service of therapies, and today we're making our first grants. These grants are an investment in human capital. They will train the next generation of scientists. Patients can celebrate today because the flow of funds has started to the physicians and scientists who have dedicated their lives to this pioneering field that holds such promise for reducing human suffering."

The Caltech program will educate postdoctoral scholars in stem cell biology, its various potential medical applications, as well as the social, ethical and legal issues in this field.

"Caltech is already undertaking many stem cell research projects, and I think this will stimulate considerable additional interest," said Paul Patterson, training program director and Biaggini Professor of Biological Sciences. "The is the first step in expanding our efforts in this area."

In addition to Caltech's current stem cell course offerings, the Institute will offer a new bioethics course that emphasizes issues raised by stem cell research and applications.

Caltech will also collaborate with the Keck School of Medicine at the University of Southern California and the Children's Hospital of Los Angeles to offer a new tri-campus lecture course in stem cell biology.

The major strengths of the training program at Caltech will be the extremely high quality of the trainee population, the strength and cross-disciplinary nature of research offerings, the research facilities, and the available and new courses.

Relevant areas of current research at Caltech include embryonic and adult stem cell plasticity, stem cells and cancer, embryonic development, imaging technology, tissue engineering and macromolecular fabrication, computational biology, nanoscale biology and chemistry, and the basic science of hematopoietic, muscle, endothelial and neural stem cells. The cells and organisms being studied in this context include yeast, C. Elegans, Drosophila, Xenopus, zebrafish, mice and humans, including a variety of animal models of human diseases.

The new, collaborative part of this training program utilizes the expertise at Keck/USC and Children's Hospital in the areas of human embryonic stem cell growth and differentiation, cutting-edge gene transfer technology application in the clinic, stem cell research in a variety of organs, as well as medical ethics. Together, these institutions can provide a broad, in-depth curriculum for trainees. This collaboration also offers the opportunity and stimulus for basic scientists to become familiar with related clinical issues and the potential application of their findings to disease.

To enhance interaction among the CIRM trainees and to keep them up to date in this field, the Caltech program will include new stem cell seminar and journal club programs, as well as an annual scientific symposium.

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Researchers Determine How Plants Decide Where to Position Their Leaves and Flowers

PASADENA, Calif.—One of the quests of modern biologists is to understand how cells talk to each other in order to determine where to form major organs. An international team of biologists has solved a part of this puzzle by combining state-of-the-art imaging and mathematical modeling to reveal how plants go about positioning their leaves and flowers.

In the January 31 issue of the Proceedings of the National Academy of Sciences (PNAS), researchers from the California Institute of Technology, the University of California at Irvine, and Lund University in Sweden reported their success in determining how a plant hormone known as auxin affects plant organ positioning. Experts already knew that auxin played some role in the development of plant organs, but the new study employs imaging techniques and computer modeling to propose a new theory about how the mechanism works.

The research involves the growing tip of the shoot of the plant Arabidopsis thaliana, a relative of the mustard plant that has been studied intensely by modern biologists. With its simple and very well understood genome, Arabidopsis lends itself to a wide variety of experiments.

The achievement of the researchers is their demonstration of how plant cells, with purely local information about their nearest neighbors' internal concentration of auxin, can communicate to determine the position of new flowers or leaves, which form in a regular pattern, with many cells separating the newly formed primordia (the first traces of an organ or structure). The authors theorize that the template the plant uses to make the larger parts comes from two mechanisms: a polarized transport of auxin into a feedback loop and a dynamic geometry arising from the growth and division of cells.

To capture the development, Beadle Professor of Biology Elliot Meyerowitz, division chair of the biology division at Caltech, and his team used green fluorescent proteins to mark specific cell types in the plant's meristem, the plant tissue in which regulated cell division, pattern formation, and differentiation give rise to plant parts like leaves and flowers.

The marked proteins allowed the group to image the cell's lineages through meristem development and differentiation leading to specific arrangement of leaves and reproductive growth, and also to follow changes in the concentration and movement of auxin.

Although the study applies specifically to the Arabidopsis plant, Meyerowitz says the mechanism is probably similar for other plants and even other biological systems in which patterning occurs in the course of development.

In addition to Meyerowitz, the paper's authors are Henrik Jönsson of Lund University, Marcus G. Heisler of Caltech's Division of Biology, Bruce E. Shapiro of Caltech's Biological Network Modeling Center, and Eric Mjolsness of UC Irvine's Institute of Genomics and Bioinformatics and department of computer science.

 

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