RESEARCH HIGHLIGHTS
Shortest Telomeres Start Cellular Death Spiral
Two Parkinson's Proteins Linked
Fat Cells and Neurons Talk in Lab Dish
DNA Copying in Yeast Has Two Controls
Single Molecules' Movement "Caught on Tape"
Two Mechanisms of Pain for Amputees?
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AWARDS AND HONORS
Solomon Snyder, M.D., Receives Two Prestigious Awards
Do you have an interesting research finding about one month from publication or presentation? Send manuscripts to Joanna Downer at jdowner1@jhmi.edu or fax to 410-955-4452. Information about awards and honors received by laboratory personnel and others is welcomed also.
RESEARCH HIGHLIGHTS
10/4/01
Shortest Telomeres Start Cellular Death Spiral
Using yeast and genetically engineered mice, Hopkins scientists have found that events associated with losing the function of telomeres, the repetitive ends of chromosomes, depend on the length of the shortest telomere in a cell, not the commonly measured average length.
Without telomere function, a cell's chromosomes can rearrange, scrambling their genetic information, halting cell division and eventually leading to the cell's death. Understanding the details may eventually provide targets for treating cancer, says Carol Greider, Ph.D., a professor of molecular biology and genetics.
In yeast, losing telomere function directly caused accumulation of genetic and chromosomal changes. Turning on telomerase, the enzyme that rebuilds telomeres, prevented this instability, the scientists reported. (Cell, 106(3):275-286, Aug. 10, 2001)
By studying individual telomere length in genetically engineered mice, Mike Hemann and others in Greider's lab showed that instability begins when one or two chromosomes' telomeres are all but gone. Furthermore, telomerase rebuilds the shortest telomeres just enough to restore function, they add. (Cell, 107(1):67-77, Oct. 5, 2001)
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10/12/01
Two Parkinson's Proteins Linked
A new study identifies an important link between the two main inherited forms of Parkinson's disease (PD), and might also connect them to non-inherited versions.
The inherited forms are marked by mutations in one of two different proteins, parkin or alpha-synuclein (aS), but how they might lead to the same disorder isn't well understood. One answer is that both proteins interact with a third protein, synphilin, and the mutations disturb this interaction, Hopkins scientists report in the October issue of Nature Medicine. (Nature Medicine, 7(10):1144-1150, Oct. 2001)
While how this disturbance might result in nerve cell death isn't known, the common thread offers clues for further studies, says Ted Dawson, M.D., Ph.D, professor of neurology and neuroscience and director of the Program in Neural Regeneration and Repair for the Institute for Cell Engineering.
"We were trying to see if the genetic mutations converge with what's known about the non-inherited disease, as is the case for Alzheimer's disease," explains Dawson. "And now, all roads in Parkinson's disease seem to lead to alpha-synuclein."
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10/16/01
Fat Cells and Neurons Talk in Lab Dish
Growing fat cells and nerve cells in the same dish has produced what is believed to be the first demonstration of two-way communication between the cell types, Johns Hopkins scientists report in the Oct. 16 online Proceedings of the National Academy of Sciences.
The achievement, using rat and mouse cells, provides the first clear evidence that signals from fat cells can directly influence neurons outside of the brain and without direction from the brain, the researchers say. The research has implications for understanding the storage and burning of fat, obesity and related disorders, such as diabetes.
"It's been known that neurons outside the brain communicate to fat cells, but no one has thought much about whether fat cells can signal back to the neurons," says first author Christine Turtzo, an M.D.-Ph.D. candidate who conducted the research under Dan Lane, Ph.D., professor of biological chemistry. "We now have evidence that fat cells directly signal neurons and influence their behavior."
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(PNAS, 98(22):12385-12390, Oct. 23, 2001)
10/22/01
DNA Copying in Yeast Has Two Controls
The crucial job of ensuring that a single genome copy gets made during cell division is shared by two independent controllers, Johns Hopkins researchers report in the Oct. 23 online Proceedings of the National Academy of Sciences.
Using engineered yeast whose division is similar to human cells, the scientists discovered that when the two controller proteins, Cdc18 and Cdt1, remain in the cell, copying continues abnormally. The Cdc18 protein helps build machinery that copies DNA, and Cdt1 helps start that machine. Usually, the proteins are destroyed after a single copy, or replication, of the DNA is made.
"Having two proteins offers redundant protection against making extra copies of DNA, which helps maintain the integrity of the genome for subsequent generations of cells," says Mark Frattini, M.D., Ph.D., a postdoctoral fellow in medical oncology and molecular biology and genetics.
Understanding this complex and tightly regulated process may help clarify what goes wrong in cancer cells, says Thomas Kelly, M.D., Ph.D., professor and director of molecular biology and genetics and director of the Institute for Basic Biomedical Sciences.
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(PNAS, 98(23):13114-13119, Nov. 6, 2001)
10/29/01
Single Molecules "Caught on Tape"
Understanding attraction is difficult enough, but it's a little less so these days, at least in amoeba living in the lab of Johns Hopkins scientist Peter Devreotes, Ph.D.
These tiny single-celled organisms have a thing for a certain molecule, called cAMP, and move toward it with striking efficiency. Using receptors distributed throughout its outer membrane, the amoeba can detect cAMP all around and constantly move toward higher concentrations of the attractant.
Similarly, directed movement, or "chemotaxis," guides human cells in their normal travels and in diseases such as arthritis, asthma, multiple sclerosis and cancer, says Devreotes, professor and director of cell biology.
In the Oct. 26 issue of Science, Japanese scientists and Devreotes describe imaging single molecules of cAMP as they interact with receptors on the surface of the amoebae, providing real-time video of how the receptors and cAMP behave.
Tagged with a fluorescent dye, the cAMP glowed when attached to its receptor. Receptors on the "front" of the cell had faster and more frequent interactions with cAMP, the images showed.
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(Science, 294:864-867, Oct. 26, 2001)
10/16/01
Two Mechanisms of Pain for Amputees?
Fifty to 80 percent of all amputees experience pain in their stumps or what feels like the missing limbs long after surgical wounds have healed. Now new research from Johns Hopkins suggests the two pains have different sources.
In a study examining stump pain vs. "phantom pain," researchers observed that the powerful pain reliever morphine significantly relieved both stump and phantom pain, while the local anesthetic lidocaine relieved only the stump pain.
"Our results suggest that different therapeutic sensitivities of stump and phantom pain to these drugs exist, and that the mechanisms of these two types of pain may differ," says Srinivasa N. Raja, M.D., professor of anesthesiology and critical care medicine at Hopkins. The report was presented Oct. 16 in New Orleans at the annual meeting of the American Society of Anesthesiologists.
Stump pain is believed to arise from nerve injuries at the site of the amputation and the resulting formation of neuromas, noncancerous tumors that grow out of the injured nerve fibers. Phantom pain is thought to reside in the brain. Details of these mechanisms aren't well understood, however.
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New Faces -- Amy Fish is the new manager of the Institutional Animal Care and Use Committee Office, the entity charged with ensuring the University and all of its institutions are in compliance with the federal laws and policies governing the use of animals in research and teaching. She can assist investigators with submitting protocols and amendments for IACUC review. In addition to helping guide investigators through the review process, she can answer questions about protocols and provide information about using specific animals. Fish's office is in 459 Ross. 410-955-3273, 410-502-5068 (fax), afish2@jhmi.edu.
MacArthur Fellows Named -- Geraldine Seydoux, Ph.D., associate professor of molecular biology and genetics has received a MacArthur Fellowship, the John D. and Catherine T. MacArthur Foundation announced on Oct. 24. The award provides $500,000 over a 5-year period. Seydoux's research focuses on the molecular machinery of reproduction and biological development. Her work on the molecular genetics of worms called nematodes has identified the mechanisms that generate germ cells, precursors of adult reproductive organs. Kay Redfield Jamison, Ph.D., professor of psychiatry, also received a MacArthur Fellowship this year.
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New Institute of Medicine Members -- Bert Vogelstein, M.D., a Howard Hughes Medical Institute Investigator and professor of oncology and pathology, and Linda P. Fried, M.D., M.P.H., professor of medicine, epidemiology and health policy and director of the Center on Aging and Health, were elected to membership of the National Academy of Sciences' Institute of Medicine. Elected last year and inducted this year were Jacquelyn Campbell, Ph.D., R.N.; Catherine DeAngelis, M.D.; Lawrence Gostin, J.D., L.L.D.; Thomas Kelly, M.D., Ph.D; Edward Miller, M.D.; Myron Weisfeldt, M.D.; and Elias Zerhouni, M.D.
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AWARDS AND HONORS:
Solomon Snyder, M.D. , director of neuroscience and Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry, has recently received two prestigious awards. On Oct. 12, the National Alliance for Research on Schizophrenia and Depression (NARSAD) awarded its Lieber Prize for Outstanding Achievement in Schizophrenia Research to Snyder at an awards ceremony in New York City. On Oct. 16, Snyder received the Institute of Medicine's Rhoda and Bernard Sarnat International Prize in Mental Health at that group's annual meeting.
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