University News

Nobel Laureate Receives US$18 Million Grant

Nobel Prize-winning chemist and physicist Ahmed Zewail has received an $18 million grant from the Gordon and Betty Moore Foundation to create the Ultrafast Science and Technology (UST) Center at the California Institute of Technology.

The center will focus on a new scientific discipline at Caltech for which Zewail has coined the name "physical biology." The field will create new ways of understanding the dynamical behavior of biological systems by directly observing them in the four dimensions of space and time.

"The idea is to combine the principles of fundamental physics and chemistry to address complexity of biology at the molecular level," explains Zewail, who won his Nobel Prize in Chemistry in 1999 for pioneering the development of the field of femtochemistry, which made it possible using lasers to freeze-frame motions taking place in a millionth of a billionth of a second.

Femtochemistry has been hailed as the breakthrough that allowed the motions of atoms in a molecule to be observed for the first time. Studies of basic life processes, however, because of their complexity, demand microscopic observation of all atoms in biological structures as those structures change.

The UST Center will be a nucleus for interactions between faculty and research assistants from the different disciplines of physics, chemistry, and biology at Caltech. The mission of the UST Center will be to develop the science and technology for imaging biological and molecular structures in space and time using diffraction, spectroscopy, and microscopy.

Systems biologists have had success in applying breakthroughs in genomics, computational sciences, and other disciplines, with the aim of explaining how cells interact as a network. The aim of physical biology is to provide an understanding of the molecular architecture and transformations essential to function--of how things go from structure to dynamic interactions to function. And for this, it is necessary to look in all four dimensions at systems, such as proteins or cells, as they go about their business.

A very recent research article from Caltech in the journal Proceedings of the National Academy of Sciences (PNAS), volume 102, page 7069-7073, dated May 17, 2005, describes an early success in four-dimensional ultrafast electron microscopy that holds considerable potential for the imaging of materials and cells as they transform. The researchers were able, using single-electron packets, to directly image the structure of rat intestinal cells in a femtosecond snapshot. A paper in Science, volume 304, page 80-84, dated April 2, 2004, provides the methodology for obtaining atomic-scale resolutions using ultrafast electrons. A patent is pending.

This recent success in imaging was commended by Sir John Thomas of Cambridge University in a highlight entitled "A Revolution in Electron Microscopy," which was published in the July 26, 2005, issue of the journal Angewandte Chemie (www.angewandte.org). Thomas said, "The development at Caltech of 4D diffraction, crystallography, and microscopy is indeed revolutionary. The door is now open for myriad explorations in the physical and biological sciences. "

Zewail is Pauling Professor of chemistry and physics at Caltech.

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.

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Columbia Dedicates $15M to Enhance Ongoing Efforts to Diversify Faculty

Representatives of Columbia University announced the dedication of US$15 million to jump start a new recruitment campaign and to accelerate other ongoing efforts to diversify its faculty. The University Trustees, at their June meeting, unanimously approved the new funding commitment.

The University seeks to add between 15 and 20 outstanding women and minority scholars to the Faculty of Arts and Sciences over the next three to five years. It also will enhance efforts underway to change the process and culture surrounding faculty searches, recruitment, hiring, retention and promotion.

The added investment and its use stem from the work of a faculty committee that advised the vice provost for diversity on key ways to step up efforts to achieve a more diverse community of scholars.

In response to their recommendations, the investment will significantly strengthen a coordinated set of initiatives that, among other things, improve the faculty hiring process to more successfully identify and recruit outstanding scholars from historically under represented groups; address the work-life issues of an increasingly diverse faculty; the acute problem of the dearth of women and minority faculty in natural sciences and engineering; and extend the University's dialogue in this important area.

The new resources will help underwrite promising efforts in various departments to widen the pools from which search committees select faculty; lengthen search time and expand recruitment efforts; experiment with strategies such as cluster hiring and coordinated appointments; create dual career and partner placement policies; undertake more interdisciplinary hiring; centrally organize information about how to access existing networks of outstanding minority and women candidates; and sponsor workshops on issues relevant to successful identification and recruitment of outstanding candidates.

Recognizing the importance of child care for recruiting and retaining outstanding faculty, the University has begun a needs assessment and feasibility study for Morningside and uptown campuses in regard to child-care. The assessment is being conducted by the Bright Horizons Child Care Corporation, which manages Columbia's Lamont Doherty Child Care Center and provides child-care services to other leading universities, such as MIT, Yale, Duke and Princeton. The report is expected in January 2006.

For historical reasons, women and minorities continue to be under-represented in some fields. The problem is particularly pronounced in the natural sciences and engineering. The vice provost for diversity, working with the New York Academy of Sciences, is establishing a consortium of area universities, medical schools and industries with a view toward creating, among other options, a high-end job bank for science positions in the New York area. This fall, the consortium will hold its second meeting, exchanging information about initiatives at peer schools; discussing strategies for building pipelines to facilitate the careers of women and minorities in academic science; and examining ways to respond to dual career problems as they arise in the sciences.

In addition, the vice provost's Task Force on Diversity in Science and Engineering has been tasked with finding ways to strengthen the pipeline bringing women and minority students into the University's undergraduate, graduate, and postdoctoral programs. The committee will work in conjunction with the National Science Foundation's ADVANCE program in the Environmental Sciences and with Columbia's Presidential Advisory Committee on Diversity Initiatives to build on, refine or modify successful initiatives undertaken by those groups. A series of working papers over the next 18 months will detail new steps to enhance diversity efforts in the fields of science and engineering.

The investment also allows for continued expansion of University-sponsored events on diversity matters. Last year's guest speakers included Princeton President Shirley Tilghman, who spoke about the hurdles of recruiting and retaining women in science; MIT Biology Professor Nancy Hopkins, who described the institutional transformation around gender issues that occurred at MIT; and Georgetown University Law Professor Chuck Lawrence, who spoke about the continuing need for affirmative action.

In the coming academic year, the Presidential Advisory Committee on Diversity Initiatives will continue to maintain the accelerated momentum. It will:

• work closely with the provost and a range of departments and centers in the Arts and Sciences to oversee the new investment;
• extend the diversity committee's work into the professional schools
• undertake information sessions for search committees starting in the fall designed to eliminate unconscious bias against diversity candidates, and to outline best practices for successful searches;
• work with ADVANCE to prepare appropriate materials and continue to sponsor events designed to extend the University conversation on diversity matters;
• encourage salary equity studies throughout the University; and
• work with the Office of Institutional Research to synchronize data collection for the Office of Equal Opportunity and other relevant offices and committees.

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U-M Researchers Awarded $6 Million to Develop New Cancer Drugs

Researchers at the University of Michigan Comprehensive Cancer Center have been awarded a US$6-million grant from the National Cancer Institute to discover and develop new drugs that target cancer cells that do not respond to current treatments. The goal is to find drugs that can be used to treat many different types of cancer.

The five-year grant is part of the National Cooperative Drug Discovery Group, an NCI initiative that supports broad, innovative and multi-disciplinary approaches to the discovery of new drugs for cancer treatment.

All cells have a built-in mechanism providing for cell death. A major characteristic of the cancer cell, which distinguishes it from the normal cell, is its resistance to such programmed cell death, known as apoptosis. This plays a major role in the cell's resistance to chemotherapy or radiation and in the failure of drugs currently used to treat cancer.

Chemotherapy and radiation for the treatment of cancer work by directly or indirectly inducing cancer cells to die. It is now known that the ability to evade cell death is a hallmark of all cancers. The central goal of this grant is to design new small-molecule drugs that specifically thwart such evasion and challenge the resistance of cancer cells to apoptosis. Such drugs will form the basis of novel strategies aimed at improving the survival and quality of life of cancer patients.

The research team proposes to design and synthesize small molecules that specifically target two critical proteins that play a role in apoptosis, Bcl-2 and Bcl-xL. Small molecules can be designed to zero in on a specific site in the protein that researchers know is important to the protein's function.

“The Bcl-2 and Bcl-xL proteins are overexpressed in many types of cancer cells, making the cancer cells resistant to conventional anticancer drugs. That makes these two proteins very attractive molecular targets for the design of an entirely new type of anticancer drug,” says Shaomeng Wang, Ph.D., associate professor of internal medicine at the U-M Medical School, who also has a joint-appointment in the U-M College of Pharmacy. Wang, co-director of the Molecular Therapeutics Program at the U-M Comprehensive Cancer Center, is principal investigator for the grant.

Traditional chemotherapy is lethal to any cell that is dividing and copying itself, which is why patients experience so many side effects, like hair loss, nausea and vomiting. New targeted molecular therapies, like the one sought here, do not harm these normal cells. The currently available drugs Gleevec and Avastin are both targeted therapies.

Kenneth Pienta, M.D., director of Urologic Oncology at the U-M Comprehensive Cancer Center and professor of internal medicine at the U-M Medical School will lead one of the three programs involved with the grant, focusing on testing the therapy in animal models. Wang's lab will design and synthesize the compounds and study how they work. A third arm of the research, led by Jeanne Stuckey, Ph.D., a research assistant professor with the U-M Life Sciences Institute and Medical School, will use X-ray crystallography to determine how these newly designed small-molecule inhibitors interact with the Bcl-2/Bcl-xL proteins. This aspect of the project will also be aided by studies with nuclear magnetic resonance methods, conducted by York Tomita, Ph.D., assistant professor at Georgetown University.

In addition to Wang and Pienta, other co-investigators on this grant include Gabriel Nunez, M.D.; Liang Xu, M.D. Ph.D.; James Rae, Ph.D.; Zaneta Nikolovska-Coleska, Ph.D.; Haiying Sun, Ph.D.; Renxiao Wang, Ph.D.; and Kent A Griffith, M.S.; all from the University of Michigan. In addition, scientists from the U-M and other institutions will serve as consultants. These include Paul Hollenberg, Ph.D., professor and chair of Pharmacology at U-M; Janet Smith, Ph.D., professor of biological chemistry at U-M; Alex Bridges, Ph.D., Quatrx Pharmaceuticals; David Kwok, Ph.D., Biopharmaceutical Research; Dennis Torchia, Ph.D., National Institutes of Health; Frederick Valeriote, Ph.D., Josephine Ford Cancer Center; and Dajun Yang, M.D., Ph.D., and Jon Holmlund, M.D., both from Ascenta Therapeutics.

The University of Michigan has partnered with Ascenta Therapeutics, a biopharmaceutical company focusing on oncology drug development, to pursue clinical development of the most promising small-molecule inhibitors of Bcl-2/Bcl-xL obtained from this research. Wang is a co-founder of Ascenta Therapeutics, serves on the board of directors and has significant financial interest in the company.

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UW-Madison Gets $3.4 Million for MS Study

In an effort to develop new techniques to repair and protect the nervous system in multiple sclerosis patients, including the use of human stem cells, the National Multiple Sclerosis Society has awarded $3.4 million to a team of UW-Madison scientists.

The group, led by School of Veterinary Medicine professor Ian D. Duncan, is developing cell transplant techniques that may one day be used to repair the damaged myelin - the critical sheathing of nervous system fibers - characteristic of the debilitating and unpredictable disease.

Multiple sclerosis - which affects an estimated 2.5 million people worldwide, 400,000 people in the United States and 10,000 in Wisconsin - involves a misdirected attack by the immune system on myelin, the nerve fiber coating that speeds the signals of the central nervous system. Multiple sclerosis also destroys the underlying nerve fiber, causing symptoms such as numbness, blindness, cognitive dysfunction and paralysis.

An important part of the Wisconsin project, according to Duncan, will be efforts to direct human stem cells to become myelinating cells that could be used in transplants to repair the nervous system lesions characteristic of multiple sclerosis.

The project, Duncan adds, will also expand studies of the antibiotic minocycline, a drug that has shown potential for protecting nerve fibers and mitigating the debilitating symptoms of multiple sclerosis. Duncan's lab has already shown that the drug has anti-inflammatory properties in an animal model of MS.

The Wisconsin team, Duncan says, plans to deploy powerful, state-of-the-art imaging technologies, including magnetic resonance imaging (MRI) and Positron Emission Tomography (PET), to image lesions and how they respond to treatment.

The work to be funded by the new grant, part of a five-year, $30 million initiative by the National Multiple Sclerosis Society, is expected to lay the groundwork for clinical trials by refining cell transplant methods and the ability to image myelin and nerve fiber damage and cell repair at work. The new initiative, known as "Promise 2010," includes a pledge of $2 million in support from the Wisconsin chapter of the National Multiple Sclerosis Society.

In addition to Duncan, UW-Madison team members include John O. Fleming, a professor of medical microbiology and neurology; Aaron Field, a professor of neurology and radiology; Su-Chun Zhang, a professor of anatomy and neurology; Andrew L. Alexander, a professor of medical physics and psychiatry; P. Charles Garell, a professor of neurological surgery; James E. Holden, a professor of medical physics and radiology; Mary Elizabeth Meyerand, a professor of medical physics and neurology; Thomas Cook, a senior scientist in biostatistics; Zsuzsa Fabry, a professor of pathology; Alex Converse, an assistant scientist at the Waisman Center; and Maria Nikodemova, an assistant scientist in medical sciences.

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British Researchers Target 'Viral-Induced Wheezing'

The treatment of a lung condition that affects almost half of all pre-school children is to be investigated by researchers at the Universities of Nottingham and Leicester.

They aim to find a definitive answer on the best way of treating the tens of thousands of children brought into hospitals every year with unexplained wheezing and shortness of breath.

The condition affecting them, known as 'viral-induced wheezing', is one of the commonest reasons for young children to be admitted to accident and emergency departments.

For many years, the standard treatment for this condition has been a short course of steroids — the same treatment commonly given to children suffering asthma symptoms.

But while asthma is thought to be triggered by allergies, viral-induced wheezing has different causes. And evidence has been accumulating recently that steroids may not, in fact, be the best approach for young children brought into hospital with viral-induced wheezing.

Researchers at the Universities of Nottingham and Leicester are now to investigate the treatment and establish definitively whether steroids are the best treatment or not.

Dr Jonathan Grigg and Dr Monica Lakhanpaul, both of the University of Leicester, are leading the study.

Steroids work by reducing inflammation in the airways. But repeated doses can suppress the body's own natural steroid production, which can have side effects on growth. So if the treatment were actually ineffective for viral-induced wheezing, such side-effects would be suffered unnecessarily.

Up to 700 children are to be enrolled onto the study from Nottingham's City Hospital, the Queen's Medical Centre, and Leicester Royal Infirmary over a three-year period. Half will be given steroids and half a placebo, and they will be followed up at one week after treatment and again at four weeks.

The study is being funded with a £200,000 (US$363,000) grant from national charity Asthma UK.

Principal investigators at the University of Nottingham are Dr Alan Smyth and Professor Terence Stephenson.

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Psychiatry Professor Wins Prestigious International Prize

Elliot S. Gershon, M.D., Foundations Fund Professor of Psychiatry and Human Genetics at the University of Chicago, has been awarded the Anna-Monika Prize, awarded once every two years by the Anna-Monika Foundation, based in Berlin, Germany, for his research on the role of genetics in bipolar disorder. The privately funded Foundation, established in 1964, promotes experimental research on the causes of depression.

Gershon will travel to Berlin on November 23, 2005, to receive the 25,000-Euro prize, (approximately $30,000), and to lecture on his research.

In 2003, Gershon's team, including colleagues Eiji Hattori, Ph.D., Chunyu Liu, Ph.D., Judith A. Badner, MD, PhD, and Susan Christian, PhD, published a landmark paper on the genetics of bipolar disorder, tracing increased susceptibility to this disease to two overlapping genes found on the long arm of chromosome 13. The study was the first to implicate this gene complex, and the second to tie any gene to the development of bipolar disorder, which affects 2 million American adults. Since this report, there have been two published replications.

"The discovery of susceptibility genes for psychiatric disorders has been one of the most intractable problems in human genetics," said Gershon. "In the past few years, we seem to have reached a watershed for psychiatric gene discovery. After years of false starts and unfulfilled promises, we have begun to make real progress."

Bipolar disorder, also knows as manic-depressive illness, is a brain disorder that causes profound shifts in a person’s mood, with spurts of high energy and elation alternating with longer periods of fatigue and deep sadness. It affects about one percent of adults, usually beginning in late adolescence. The disorder is caused by multiple genes, each contributing a small part. The bipolar gene on chromosome 13 has a "weak effect," said Gershon, increasing susceptibility to the disease by about 25 percent.

Gershon, routinely named in the publication "The Best Doctors in America" for care of patients with mood disorders, earned his B.A. and M.D. from Harvard. He came to the University of Chicago as chairman of the department of psychiatry in 1998 from the National Institute of Mental Health, where he was chief of the Clinical Neurogenetics Branch. He stepped down as chairman last year.

A member of the editorial boards of several psychiatric journals, and past president of the American Psychopathological Association, Gershon has edited four books and written more than 350 articles on the neurobiology, genetics and treatment of mental disorders.

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Princeton’s Hopfield Earns Einstein World Award of Science

Princeton Professor John Hopfield has been selected to receive the 2005 Albert Einstein World Award of Science by the World Cultural Council.

The award usually is given in recognition of an outstanding contribution to a discipline within the pure or applied sciences that has benefited the human race. Hopfield is being honored for his contributions to three major disciplines -- physics, chemistry and biology -- and for his ability to cross boundaries "to discover new questions and propose answers that uncover the conceptual structure behind the experimental facts," according to the council.

Hopfield currently is the Howard A. Prior Professor in the Life Sciences at Princeton, where he joined the faculty as a professor of physics in 1964. In 1969, only 11 years after earning a Ph.D. in physics from Cornell University, he received the American Physical Society's Buckley Prize for his research on the emission and absorption of light by semiconductors.

Over the next several years, Hopfield switched his research focus from physics to biology and earned an international reputation for his pioneering applications of physics-related computational techniques to the emerging field of neurobiology. He has worked to develop a theoretical understanding of how the neural circuits of the brain perform complex calculations, investigating the way in which nerve cells work together to process sensory perceptions such as the recognition of odors or sounds. The Hopfield model of neural processing, which provides insight into the differences between computation in computers and the brain, has become widely referenced in the field.

The recipient of a MacArthur Foundation Award in 1983, Hopfield also received the American Physical Society's Prize in Biophysics in 1985 as well as the Dirac Medal from the Abdus Salam International Centre for Theoretical Physics in 2001. He is a member of the American Academy of Arts and Sciences and the National Academy of Sciences. Between 2000 and 2002, he served on an NAS panel on undergraduate biology education for future scientists.

A professor of chemistry and biology at the California Institute of Technology from 1980 to 1997, Hopfield returned to Princeton as a professor of molecular biology in 1997 and was named to the endowed professorship in 2002. He also serves on the faculty of Princeton's Lewis-Sigler Institute for Integrative Genomics.

The Albert Einstein World Award of Science will be presented Nov. 12 during a ceremony at the Universidad Autónoma Agraria Antonio Narro in Saltillo, Coahuila, México. The World Cultural Council is an international organization based in México that annually acknowledges individuals or institutions for outstanding achievements in science, education and the arts. During the same ceremony, Mexican architect Enrique Norten will receive the Leonardo da Vinci World Award of Arts. 

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MIT Finds Genetic Clue to Bone and Fat Production

MIT researchers have identified a gene that helps control the balance between bone and fat in the human body, a discovery that could pave the way for the prevention of childhood obesity and the treatment of osteoporosis.

The findings will be published in the Aug. 12 issue of Science.

Researchers at MIT's Center for Cancer Research found that a gene called TAZ works to control the destiny of adult bone marrow stem cells, also known as mesenchymal stem cells (MSCs). MSCs have the potential to form a number of different cell types, including bone, fat and muscle.

"We show that a single molecule helps turn one set of genes on to form bone and another set of genes off to inhibit fat formation in MSCs," said Michael Yaffe, the Howard and Linda Stern Professor of Biology and senior author of the paper. "This result suggests a potential new approach to combating various human diseases that result from a disruption in the balance between bone and fat."

The research presents several therapeutic opportunities, including the possibility that once isolated from the bone marrow, MSCs could be useful for healing bone fractures.

It would also be interesting to investigate whether TAZ activity is defective in bone tumors, and in bone-like tumors that form from fat cells, the researchers said. Modulating TAZ activity could be an effective approach to treating these tumors.

The researchers studied the function of TAZ in cultured MSCs and in animals. MSCs comprise a small percentage of bone marrow cells, about 0.01 percent.

The researchers' most stunning result came when they injected one- to two-cell zebrafish embryos with short strands of RNA that blocked expression of the TAZ gene.

"When we knocked out TAZ in zebrafish, the embryos died when they were just 8 days old, and they had failed to form any bones at all," said postdoctoral fellow Jeong-Ho Hong, the lead author on the paper. Therefore, depletion of TAZ within the body completely impaired bone development. When TAZ was depleted in MSCs grown outside the body in culture, those cells readily turned into fat.

The research was borne out of a collaboration between Yaffe, who also holds appointments in the Broad Institute and in the Department of Surgery at Beth Israel Deaconess Medical Center; Harvard Medical School; the CCR labs of Nancy Hopkins, Amgen Professor of Biology, and Phillip Sharp, Institute Professor of biology; and the lab of Bruce Spiegelman at the Dana-Farber Cancer Institute and Harvard Medical School.

MIT CCR researchers Michael T. McManus, Adam Amsterdam and Ralitsa Kalmukova, Harvard Medical School researchers Eun Sook Hwang of the Harvard School of Public Health, Yu Tian and Thomas Benjamin of the Department of Pathology, and Elisabetta Mueller and Bruce M. Spiegelman of the Dana-Farber Cancer Institute and the Department of Cell Biology also contributed to this work.

Support for this work comes from the National Institutes of Health and the Burroughs-Wellcome Fund.

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Stanford’s Solar Car Team Wins 1st Place

The Stanford University Solar Car Racing team is the first-place winner in their class for the North American Solar Challenge. On July 26, the solar-powered car, Solstice, completed the ten-day race from Austin, Tex., to Calgary, Canada—a distance of 2,500 miles.

There were four team members who took turns driving Solstice and 11 other members who went out with them for the race. Over the course of the competition, the vehicle whizzed at up to 65 miles per hour.

The road to success, however, wasn't without a few bumps. At the starting line, the team encountered a circuit malfunction caused by a loose wire. "We got off about a half an hour late at the starting line, which ended up putting us about two or three hours behind," says team member Carrie Bobier, an undergraduate in mechanical engineering.

Once the team got on the road, the car ran smoothly until just hours later when the driver encountered a Texas thunderstorm. The solar car's hatch wasn't waterproof, so rain began leaking through cracks and two ventilation ducts, eventually causing water to pour onto the driver's lap and on the circuit breakers.

Toward the end of the race, the team ran into a problem, literally. A miscommunication between the driver of the solar car and the team's chase van resulted in the chase van rear-ending Solstice at a stoplight, damaging 54 solar cells. Team members ended up spending their day off in Medicine Hat, Canada, replacing the broken cells and repairing minor body damage.

The racers set off on the next and final day of the competition in the lead, but the team members realized that they had forgotten to turn on the parts of the solar array they had replaced.

Not wanting to lose the lead, Hantsoo and his teammates kept the car rolling. One vehicle caught up to Solstice but didn't pass, thinking the Stanford team was employing some kind of strategy, Hantsoo says. But the Stanford group soon became disheartened when its main competitor, CalSol from the University of California-Berkeley, passed Solstice just 30 miles from the finish line. Then, when Stanford's chance of winning looked the most bleak, within five miles of the finish line, CalSol malfunctioned and had to pull over to the side of the road, allowing Solstice to re-gain the lead.

After a late start and a nail-biting end, the Stanford Solar Racing team made it to the finish line in 68 hours and four seconds, winning first place in its class. While some team members say they can empathize with team CalSol, they all are pleased with the car's performance and the team's determination.