MIMG NEWS
California Awards Comprehensive Stem Cell Reseach Grants;
Date: March 16, 2007 Scientists at the Institute for Stem Cell Biology and Medicine at UCLA today received two comprehensive research grants from the state as part of the second round of funding for embryonic stem cell research since voters approved Proposition 71 in November 2004. The two UCLA grants total more than $5 million over four years and will be used to fund research on neural cell repair and therapeutic strategies to target HIV. The grant submitted by Guoping Fan, UCLA assistant professor of human genetics, scored 95 points out of 100 — the highest score awarded to any grant by the selection committee during this round of funding. The California Institute of Regenerative Medicine (CIRM), the state organization that oversees Proposition 71 funding, received 70 grant applications totaling more than $175 million from researchers at 23 nonprofit institutions. Of those, 29 were funded, totaling $75 million. Dr. Owen Witte, renowned scientist and director of the Institute for Stem Cell Biology and Medicine at UCLA (ISCBM), said he was pleased that two UCLA researchers were awarded grants. “These grants are given to scientists with a record of accomplishment in stem cell research, and I’m proud to have two ISCBM researchers among the grant winners, which represent the top scientists in California,” Witte said. “This funding will enable us to continue fostering leading-edge interdisciplinary collaborations and build upon our existing body of knowledge in stem cell science for the benefit of people worldwide.” The funded grants at UCLA include:
Fan’s research will compare the quality and potential of eight human embryonic stem cells lines in their capacity to become nerve cells; examine the levels of gene expression and the mechanisms that control gene expression in human embryonic stem cell-derived nerve cells to determine how these cells compare to nerve cells in normal human beings; and, using a mouse model, test if human embryonic stem cell-derived nerve cells can repair the brain after stroke or injury. “We hope our study will pave the way for the future use of human embryonic stem cell-derived nerve cells in the clinical treatment of nerve injury and neurodegenerative diseases such as stroke and Parkinson’s disease,” Fan said. “Considering the restricted federal funding for research with human embryonic stem cells, the CIRM awards come at the perfect time.”
Zack, associate director of the UCLA AIDS Institute, will test three different types of anti-HIV gene therapy approaches in laboratory models. The different genes will be inserted into human embryonic stem cells, and those cells will be allowed to develop into blood cells. Researchers will then test whether “therapeutic” genes can inhibit HIV infection in a cell culture. Zack also will develop mouse models that allow development of human embryonic stem cells into blood cells in the body. He will test the efficacy of the genetic approaches in these systems, as they most closely represent the situation in humans. Zack said his research will “provide proof-of-principle that cells in the immune system can be modified by manipulation of human embryonic stem cells.” “This may help us develop future therapeutic approaches to combat HIV,” he said. “These studies also will be relevant to other immune system disorders, such as autoimmune diseases.” Comprehensive grants are intended to support mature, ongoing studies on human embryonic stem cells by scientists with a proven record of accomplishment in the field, CIRM officials said. The grants offer opportunities for investigators with well-developed expertise in human embryonic stem cell research or closely related stem cell fields to expand their programs or take promising new directions based on current research. The grant applications were reviewed by a committee composed of scientific experts from outside California and patient advocates from the Independent Citizens Oversight Committee, the CIRM’s governing board. The oversight committee approved the grants today during its meeting in the Los Angeles area. Last month, scientists from UCLA’s Institute for Stem Cell Biology and Medicine received seven of 72 state seed grants. The grants totaled more than $4 million over two years. Seed grants are intended to bring new ideas and new investigators into human embryonic stem cell research. The Institute for Stem Cell Biology and Medicine was launched in 2005 with a UCLA commitment of $20 million over five years. The institute is committed to a multidisciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The institute supports innovation, excellence and the highest ethical standards focused on stem cell research, with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The institute is a collaboration of the David Geffen School of Medicine at UCLA, UCLA’s Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science, and the UCLA College of Letters and Science. For more information, visit www.stemcell.ucla.edu. -UCLA- KIER124 |
UCLA and NYU Microbiologists Decipher
Date: January 17, 2007 Scientists at UCLA and NYU have deciphered the genome of the parasite causing trichomoniasis, and their research may lead to new approaches to improve the diagnosis and treatment of this common sexually transmitted disease. Trichomoniasis affects an estimated 170 million people a year, with more than 5 million cases reported in North America. This global health problem results when the single-celled parasite Trichomonas vaginalis sets up house in the reproductive tract. Led by Patricia Johnson, a UCLA professor of microbiology in the department of microbiology, immunology and molecular genetics, and Jane Carlton, an associate professor in the department of medical parasitology at New York University School of Medicine, the team of scientists took four years to crack the surprisingly large genome of this parasite. They published the draft sequence of the parasite’s genome in the Jan. 12 issue of the journal Science. “Patricia Johnson cloned the first Trichomonas vaginalis gene in 1990 as an assistant professor at UCLA, and it is tremendously gratifying that she is now senior author on a landmark publication describing the entire genome,” said Jeffery F. Miller, chair of microbiology, immunology and molecular genetics at UCLA and UCLA’s M. Philip Davis Professor of Microbiology and Immunology. “The implications of this work range from fundamental insights into early evolution to understanding pathogenesis and developing drugs and vaccines. This is a major accomplishment in the field.” “T. vaginalis is an extremely successful parasite, capable of establishing and maintaining infections in both men and women,” Johnson said. “Symptoms vary greatly among infected individuals, and the reason for this wide range of variable pathogenic outcomes is poorly understood. Among the many new insights brought by deciphering the genome sequence of this organism are ones that provide new clues for identifying critical factors that are responsible for pathogenesis.” In women, the parasite binds to the vaginal lining and is capable of destroying vaginal epithelial cells, which make up the surface of this tissue, Johnson said. This results in vaginitis, with irritation of local tissues. Erosion of cervical tissues may occur, and complications can result in sterility. A big threat from infection also occurs in pregnant women, who are at risk for ruptured membranes, preterm deliveries and low-birth-weight babies. In men, the parasite is a cause of nongonococcal urethritis, but infection is generally asymptomatic and self-limiting. In both men and women, trichomoniasis is known to increase susceptibility to HIV, the virus that causes AIDS. “In countries where AIDS runs rampant, such as South Africa, the incidence of trichomoniasis is also extraordinarily high, and trichomoniasis is thought to have significantly contributed to the spread of HIV,” Johnson said. To survive, T. vaginalis must adapt to multiple microenvironments and changes in the reproductive tract. A critical property of infection is the parasite’s ability to adhere to human cells and to kill neighboring cells. “The sequence of its genome now reveals a number of factors, including putative adhesion proteins and secreted factors that may result in killing of human cells,” Johnson said. “Should future studies confirm a critical role for these, they could provide important therapeutic targets.” Currently, only one class of drugs — nitroimidazoles — is licensed for treatment of trichomoniasis in the United States, and the emergence of parasite strains that are resistant to these drugs is on the rise. There is a clear need to develop additional effective drugs, Johnson said. The T. vaginalis genome project began in 2002 and was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The first draft sequence was available in 2003, but it took years of additional work by 66 scientists in 10 countries, with expertise in cell biology, biochemistry and bioinformatics, to complete the work reported this week in Science. In addition to providing putative pathogenic and therapeutic targets, the genome could help with diagnostics too. “This genome contains a large number of repeat sequences, which could be used to devise a diagnostic test that would specifically identify this pathogen,” said researcher Jane Carlton from New York University. The parasite’s large genome has nearly 26,000 confirmed genes, which is on par with the human genome. There may be an additional 34,000 unconfirmed genes, bringing the total gene count to about 60,000. “T. vaginalis has one of the highest gene counts of any organism in the microbe, animal or plant community, probably because of the puzzlingly high number of genes repeated in the genome,” Carlton said. The scientists say they still plan to work on a final gene count. “The genome was much, much bigger than we had expected, actually 10 times what we had expected,” Carlton said. All other previously sequenced parasites had much smaller genomes. T. vaginalis is typically a pear-shaped organism, but when it sticks to the vaginal wall, the parasite flattens and dramatically increases its surface area. The scientists hypothesize that this trait brought the microbe a selective advantage during its evolution: A parasite with a big surface area, enabled by a big genome, is better at colonizing the area it is infecting. The organism also shows predatory behavior. It “eats up” good bacteria in the vagina using a process called phagocytosis. This makes the vagina more alkaline and more hospitable toward Trichomonas and other pathogens. This little bug presented a sizable genomics challenge. “The big issue is that we don’t really have the capability of dealing with a genome like Trichomonas,” Carlton said. The sequencing technology and the computer algorithms typically used to assemble and align sequenced gene fragments with computers are not available to deal with this parasite. The cause of the headache for researchers: the repeats in the genome. To sequence a genome, it is broken down into “reads,” which are snippets of DNA with 600 units, or bases. Computer programs then identify similar reads — the ones with overlapping fragments of the same sequence. These fragments are then collapsed into contiguous sequences, or “contigs,” so the genome is put back together like a jigsaw puzzle. Because Trichomonas has many repeating sequences, the computer algorithm got completely stuck. It could not assemble the contigs. The scientists were stumped. Only after bioinformatics experts and software engineers, including colleagues Steven Salzberg, Arthur Delcher and Michael Schatz from the University of Maryland, reworked the algorithm to tackle the informatics challenge could the genome project proceed to the draft now published. “This project provides a good example of the most productive way to approach scientific research that relies on cutting-edge, advanced technologies, as so many projects do these days,” Johnson said. “A coordinated, synergistic team effort involving many dedicated scientists with different expertises and perspectives and a strong drive to succeed — that’s what it takes.” About UCLA California’s largest university, UCLA enrolls approximately 38,000 students per year and offers degrees from the UCLA College of Letters and Science and 11 professional schools in dozens of varied disciplines. UCLA consistently ranks among the top five universities and colleges nationally in total research-and-development spending, receiving more than $820 million a year in competitively awarded federal and state grants and contracts. For every $1 state taxpayers invest in UCLA, the university generates almost $9 in economic activity, resulting in an annual $6-billion economic impact on the Greater Los Angeles region. The university’s health care network treats 450,000 patients per year. UCLA employs more than 27,000 faculty and staff, has more than 350,000 living alumni and has been home to five Nobel Prize recipients. -UCLA- SW024 |
NEW BUILDINGS IN PROGRESS
