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RESEARCH BRIEFS
Protein-Protein Interactions Mapped for C. elegansFirst came the genome, followed by the transcriptome, the proteome, and now the interactome. In their quest to understand how proteins get together to form the network of life, researchers from HMS and other institutions have mapped more than 4,000 physical interactions between proteins from the nematode C. elegans. The study is the first large-scale analysis of C. elegans protein- protein interactions and only the second such map of a multicellular organism, following the publication of a fruit fly interactome last year.
In the C. elegansinteractome, single proteins (circles) partner up (indicated by lines) to form an interconnected network that controls cell function. The inset details a small part of the network. (Image courtesy of Marc Vidal) "With the genome sequences behind us now, it looks as if those units of function, genes and proteins, are only the tip of the iceberg," said Marc Vidal, HMS associate professor of genetics at the Dana-Farber Cancer Institute and senior author of the study that appeared in Science online Jan. 2 and in the Jan. 23 print edition. "The rest of the iceberg is the protein network, organized by physical interactions between proteins," he said. Vidal and his colleagues tested almost 2,000 C. elegans genes in a high-throughput assay for pairwise protein interactions carried out in yeast. Even with this prodigious effort, Vidal estimates that they captured only about five to 10 percent of all the interactions that probably occur in the worm. And the map certainly contains some false positives, in which proteins that can get together in the yeast assay never actually meet up in real life in C. elegans. Nevertheless, the map will enable biologists to develop hypotheses about the function of the thousands of uncharacterized proteins in C. elegans. By combining interactome data with the other "omes" that tally global gene expression, protein localization, and functional data, Vidal hopes to see his map evolve into an atlas that will reveal the higher-order organization of multicellular organisms. --Pat McCaffrey
Reading Expressions: A Skill Toward Becoming A Better Doctor?Neuroscience is filling textbooks with new information at such a fast pace that medical students might wish for a pill that would enhance their ability to keep up with it. The good news: memory- and learning-enhancing drugs are not in the realm of science fiction anymore. The bad news: they will not make students better doctors."We will probably have these performance-enhancing drugs in a five- or 10-year horizon. I think that they will be good for some of our patients, but I'm not so sure about our students," said Ken Kosik, HMS professor of neurology at Brigham and Women's Hospital. He was speaking on Jan. 23 at the "Symposium on the Science of Learning: Implications for Medical Education from the Neurosciences and the Social Sciences." One of the themes to emerge from the event, sponsored by the HMS Office of Educational Development and the HMS Academy, is that doctors have much more to learn than facts. "A fundamental factor of being a good doctor involves empathy for our patients," Kosik said. Yet studies show that when asked to identify emotionally expressive faces, physicians do not perform well. The symposium, which comes as HMS undertakes a major renovation of its curriculum, seemed to offer up a challenge: how do we cultivate emotional and social skills in our students? Presenters drew on a wealth of studies to show how important empathy and, more generally, the emotions are in everyday life. Kosik described one study showing how subjects, when viewing emotionally expressive faces, exhibit activity in the motor areas of their brain as though they were imitating the same expression themselves. Another study showed how this internalized motor activity is accompanied by activity in the amygdala, the emotional center of the brain. On first glance, such information may appear to compound the problem facing medical educators. After all, one of the major hazards for young doctors is emotional burnout. "Too much empathy can be disabling," said Kosik. One way around this would be to enable students to be mindful of their tendency to imitate emotions while cultivating their ability to discern emotions in others. "Studies in reading faces might be worth including in a medical curriculum," he said. --Misia Landau
High Intake of Vitamin D Supplement May Cut Risk of Multiple SclerosisA new study from HSPH found that women with a high intake of vitamin D from multivitamins were less likely to develop multiple sclerosis than women who did not take vitamins.In the first prospective study to look at the relationship between dietary vitamin D intake in women and MS, researchers tracked the diets of 185,000 women in the Nurses' Health Study and Nurses' Health Study II from 1980 to 1999. During the project, 173 women developed MS. Women with the highest levels of vitamin D intake via supplements (400 international units per day or more) had a 40 percent reduced risk of developing MS compared with women who did not use vitamin supplements. High intake of vitamin D from food alone did not reduce risk. Since the women in the study got most of their vitamin D from multivitamins, researchers looked for an association of MS risk with other vitamins, but found none. Multiple sclerosis is a chronic disease of the central nervous system that affects 250,000 to 350,000 people in the United States. The prevalence of MS is higher among people who live north of the 37th parallel, which runs from San Francisco to southern Virginia, compared with those in more southerly locations. This geographic distribution and other research supports the idea that vitamin D, produced in the skin upon sun exposure, might protect against the disease. "These results are encouraging. We have suspected that vitamin D may play a role in reducing the risk of developing MS," said Kassandra Munger, a researcher in the HSPH Department of Nutrition and lead author on the study, which appears in the Jan. 13 Neurology.
Nuclear-export Inhibitors Found in Cell-based ScreenSince the transport of proteins into and out of the nucleus controls cell growth, any disruption of the import/export balance may lead to cancer. Now HMS researchers have discovered small molecules that can correct imbalances of trade by blocking nuclear export of the growth-regulating FOXO1a, a Forkhead transcription factor. Their work, published in the December Cancer Cell, identifies several new inhibitors of general nuclear export and reveals a novel feature of export controlled by the tumor suppressor PTEN. Compounds like these inhibitors, which force nuclear localization of FOXO1a, may be useful as cancer therapeutics.In what she called a "perfect synergy," Pamela Silver, HMS professor of biological chemistry and molecular pharmacology at the Dana-Farber Cancer Institute, teamed up with DFCI scientists William Sellers, HMS assistant professor of medicine, and Thomas M. Roberts, HMS professor of pathology, and the HMS Institute of Chemistry and Cell Biology's Jon Clardy, a BCMP professor, on a multidisciplinary hunt for nuclear-export inhibitors. They started with PTEN-deficient cells in which most of FOXO1a is exported from the nucleus and appears in the cytoplasm. After treating the cells with candidate export inhibitors, the researchers eyeballed thousands of magnified cell images, looking for a fluorescent signal that would show FOXO1a clustered in the nucleus. Of 18,000 chemicals tested, 42 caused nuclear localization of FOXO1a. Of these positive "hits," about half inhibited the nuclear export of multiple proteins via a common export pathway. The other hits specifically inhibited export of FOXO1a, a pathway regulated by PTEN. Some of the PTEN pathway inhibitors affected the calcium-binding protein calmodulin, revealing for the first time a role of this protein in PTEN signaling. The FOXO1a assay has been used to screen nearly 100,000 chemicals so far, and similar assays could be used for other cancer-related proteins that depend on nuclear localization. --Pat McCaffrey |
