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MILESTONE SYMPOSIA
Symposium Explores Cell Cycle and CancerCells progress through cycles and so do cell biologists. No sooner do they solve one problem than an old one presents itself for reappraisal. The familiar textbook image of chromosomes arranged along the cell's midline during mitosis has recently become an icon of mystery as biologists seek out the molecular players controlling cell division."What goes around comes around. The problems keep reappearing," said Joseph Martin, dean of the Faculty of Medicine at HMS. Martin's comment came at the end of the second Milestone Symposium, which was held on Oct. 23 and focused on the cell cycle and cancer. The question of how cells keep track of their chromosomes during cell division was only one of several longstanding problems revisited at the symposium, the second in a series commemorating the 100th anniversary of groundbreaking for the original Quadrangle. Critical CheckpointsCells monitor their chromosomes through the spindle checkpoint proteins, said Andrew Murray, professor of biology at Harvard University. Spindles attach to the kinetochores of homologous chromosomes, pulling them apart, thereby ensuring that each daughter cell receives a copy of the genetic material. Murray described how mistakes, such as unattached or poorly connected kinetochores, are picked up by the spindle checkpoint proteins lpl1 and Mad 2 and 3. Intriguingly, these proteins can become defective with age. "Our argument is that defects in the spindle checkpoint may have something to do with Down's syndrome," he said.The question of aging has been given new life in recent years with the discovery that the tips of the chromosomes, or telomeres, erode with each cell division. This dwindling of telomeres, and their formative enzyme telomerase, determines a cell's life span. Stephen Elledge, the Gregor Mendel professor of genetics and of medicine at HMS, described his efforts to identify the genes that regulate telomerase and how they are disrupted in cancer. "Ninety percent of tumors express active telomerase," he said. "We might expect that regulators of telomerase are mutated in cancer." "All the problems of biology are deeply connected," said Systems Biology chair Marc Kirschner, who moderated the symposium. Meaningful Genetic SilenceIllustrating the point, the next speaker, Danesh Moazed, described how telomeres are actually made up of long stretches of silent DNA, or heterochromatin. Moazed, HMS assistant professor of cell biology, and his colleagues have been trying to understand how this genetic silence is maintained, and have focused their attention on members of the Sir family of proteins.Few questions have a longer pedigree than how oocytes mature into eggs. Even here, recent investigations are yielding surprising results, said Joan Ruderman, the Marion V. Nelson professor of cell biology. For example, the hormone progesterone appears to turn oocytes into eggs by activating the estrogen receptor. Building on this insight, Ruderman and her colleagues have been exploring how environmental toxins, which can mimic or block hormones, may be disrupting progesterone signaling, and hence fertility. "The system is very powerful for studying an area that can have devastating effects on aquatic species, and ultimately on humans, through the food chain," she said. Addressing these new challenges, as well as old problems, will be difficult, said the last speaker, Timothy Hunt, 2001 Nobel laureate in physiology or medicine from the Imperial Cancer Research Fund, London. "The trick is to integrate all these signals from outside the cell and how they bring about the activity of all these enzymes," he said. "In addition you have got to understand the flux. It is a formidable problem." --Misia Landau |
