This is the twice-per-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Direct comments or questions to Joanna Downer, PhD, in the Office of Corporate Communications (4-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
+ Nitric Oxide Shuts Down Key Protein In Parkinson's Disease
+ Stolen Genetic Material Offers No Benefit to HIV
+ Microtubule Dysfunction Is Behind Complex Obesity Syndrome
+ Study: New Neurons Can Get Out of Spinal Cord
NEWS BRIEFS:
Harvard's Thier To Give Annual Thayer Lecture May 18
Broadway Building "Grand Opening" Set For May 25
"Enhancing Humane Science" Course Available Online
AWARDS AND HONORS:
Boatman Receives White House Career Award
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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 410-614-8951. Information about awards and honors received by laboratory personnel and others is welcomed also.
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RESEARCH HIGHLIGHTS:
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4/22/04
Nitric Oxide Shuts Down Key Protein In Parkinson's Disease
Johns Hopkins researchers have discovered that nitric oxide, a critical chemical messenger, also shuts down a protein involved in Parkinson's disease. The findings were published online in Science on April 22.
The finding biochemically links Parkinson's disease (PD) that occurs in families and the vast majority of cases, and gives researchers a brand new target for developing treatments to slow or stop the disease.
The protein in question is parkin, and earlier research had shown that mutations that cripple it occur in about a third of patients with familial PD, but rarely show up in the much more common sporadic cases of the disorder. In the absence of these mutations, however, scientists weren't sure how, or even whether, malfunction of parkin was involved in the disease.
The Hopkins team reports that nitric oxide (NO) binds to parkin and reduces its normal ability to mark proteins -- including itself -- for destruction. However, in animal models of PD, there's so much NO on parkin that the protein doesn't work at all. Moreover, NO modification of parkin was two to three times higher in brain tissue from patients with PD than in those without the disease, the researchers report.
"This tells us that very effective NO scavengers, ones that cross the blood brain barrier and enter neurons, could be potential drugs to treat Parkinson's disease," says Ted Dawson, MD, PhD, professor of neurology and neuroscience and co-director of the Program for Neural Regeneration and Repair in Hopkins' Institute for Cell Engineering.
http://www.hopkinsmedicine.org/Press_releases/2004/04_22a_04.html
Science (Published online in Science Express, April 22, 2004; print issue to come.)
http://www.sciencemag.org/cgi/content/abstract/1093891v1
(An individual subscription is required for full-text access.)
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4/23/04
Stolen Genetic Material Offers No Benefit to HIV
Viruses like HIV evolve and survive in part by "stealing" genetic ideas -- and copying genetic material -- from the human cells they infect, largely to improve their chances of infecting even more cells.
However, Johns Hopkins researchers have discovered an example of this "molecular piracy" between HIV and human cells that seems not to benefit either one. In the April 23 issue of Molecular Cell, the researchers describe an HIV protein that closely matches a protein they've been studying in heart cells. When the two proteins bind each other, neither can work, the researchers report.
"If the proteins hadn't interacted, or if there'd been no effect, we would have dropped it," says Eduardo Marban, MD, PhD, the Michel Mirowski Professor of Medicine, chief of cardiology and director of the Institute for Molecular Cardiology at Johns Hopkins. "But at each step, the results showed the proteins' similarities weren't just coincidence."
Graduate student Kate Hsu stumbled across the similarities between the HIV protein, Vpu, and their heart cell protein, a potassium channel protein called TASK-1, while searching databases for proteins that might work like TASK-1. Vpu normally helps release new copies of HIV from infected cells, but scientists know it isn't required for the virus to survive.
While unlikely to lead to new HIV treatments, the discovery could reveal interesting tidbits about how HIV behaves in cells that make a lot of TASK-1, such as heart and brain cells, versus cells that make only a little, including white blood cells, say the researchers. It could also reveal a lot about how different cells react to or are affected by HIV infection.
http://www.hopkinsmedicine.org/Press_releases/2004/04_23_04.html
Molecular Cell April 23 2004;14(2):259-267
http://www.molecule.org/content/article/fulltext?uid=PIIS1097276504001832
See also a "Preview" on this topic in the same issue:
http://www.molecule.org/content/article/fulltext?uid=PIIS1097276504002059
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4/25/04
Microtubule Dysfunction Is Behind Complex Obesity Syndrome
An international team of researchers has discovered how disruption of a single gene contributes to a complex syndrome characterized in part by insatiable appetite, they report May issue of Nature Genetics.
Bardet-Biedl syndrome (BBS), characterized by obesity, learning disabilities and eye and kidney problems, is caused by genetic mutations in the BBS family of genes. Now, researchers who've long studied the condition have discovered that genetic mutations in one of those genes, called BBS4, lead to cell death by disrupting the cells' internal "highway" system.
In experiments with human and mouse cell lines, the researchers found that the BBS4 protein normally transports molecules that help guide the cell's internal highway system -- a network of so-called microtubules along which tiny motors push and pull proteins, cellular packages and even chromosomes. When the BBS4 gene doesn't work correctly, the highway system falls apart, cell division halts and the cell dies.
"Once we knew faulty BBS4 prevented correct microtubule construction and led to cell death, the big question was how do people survive when every cell contains these mutations?" says Nicholas Katsanis, PhD, head of the team's contingent from the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins.
The key is that the BBS4 protein acts through another protein, called PCM1, or pericentriolar material 1 protein. The two proteins are found together only in certain cell types in a specific subset of tissues, so it is only in those cells that BBS4 mutations can lead to cell death, the researchers report.
http://www.hopkinsmedicine.org/Press_releases/2004/04_25_04.html
Nature Genetics 2004;36(5):462-470 (Published online April 25)
http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v36/n5/full/ng1352.html
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4/28/04
Study: New Neurons Can Get Out of Spinal Cord
In experiments with rodents, Johns Hopkins scientists have used properly directed stem cells to successfully overcome what is thought to be a basic hurdle in restoring function to severely damaged central nervous systems -- getting new motor neurons to migrate through the spinal cord.
In their experiments, the researchers first coaxed embryonic stem cells from mice to begin their transformation into motor neurons. Once these "pre-motor neurons" were implanted into the spinal cords of paralyzed rats, a constant drip of molecules that block the nerve-repelling activity of the spinal cord's myelin sheath gave the cells a chance to break through.
About 80 of an initial 12,000 neurons-in-training implanted into each rat became full-fledged motor neurons and pushed their finger-like extensions, called axons, through the spinal cord, the researchers reported April 26 in the Advance Online section of the Proceedings of the National Academy of Sciences.
"We think that getting new motor neurons to travel properly through the cord is the major hurdle to try to restore muscle control," says Douglas Kerr, MD, PhD, an assistant professor of neurology. "It's significant that axons from these motor neurons make it outside of the cord."
However, he cautions that much remains before stem cells or cells derived from them could be useful for restoring lost or "broken" neurons in people. For example, in their experiments, even though some of the new neurons reached through the myelin coating, they didn't get much farther down the road to the real target -- muscles.
http://www.hopkinsmedicine.org/Press_releases/2004/04_28_04.html
PNAS May 4 2004;101(18):7123-7128
http://www.pnas.org/cgi/content/full/101/18/7123
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Harvard's Thier To Give Annual Thayer Lecture -- Samuel O. Thier, MD, professor of medicine and health care policy at the Harvard Medical School and Massachusetts General Hospital, is scheduled to give the 48th Annual William Sydney Thayer and Susan Read Thayer Lectureship in Clinical Medicine, beginning at 4 pm, Tuesday, May 18, in Turner Auditorium. His lecture is entitled "The Future of Academic Medicine: The Hopkins Legend." For more information, email: thayerlectureship@jhmi.edu .
Broadway Building "Grand Opening" Set For May 25 -- Various events on May 25 will mark the official "grand opening" of the new research building at the corner of Madison and Broadway. The building is home to the department of comparative medicine, the Institute for Cell Engineering, the High-throughput Biology (HiT) Center and the McKusick-Nathans Institute of Genetic Medicine, and is the "front door" for the School of Medicine's administrative and leadership offices. Director of the National Institutes of Health Elias Zerhouni, MD, who pushed for the building during his tenure at Hopkins, will speak starting at 1:30 in Turner Auditorium. Tours of laboratory facilities in the new building will begin at 2:15, and a reception in Turner Plaza will start at 4 pm. All employees are invited to these three events.
http://www.insidehopkinsmedicine.org/news/leadershipcorner/2004/042904.cfm
"Enhancing Humane Science" Course Available Online -- The Center for Alternatives to Animal Testing is offering a web-based course, Enhancing Humane Science/Improving Animal Research, which provides a broad overview of topics in approaches to and practice of humane animal research. Individuals completing the self-paced, online material are invited to join a discussion group on Wednesday, May 12, from noon until 1:30 pm in Room W3030 in the Bloomberg School of Public Health. The course offers a certificate of participation. For more information, contact mgoldberg@jhsph.edu or jowiny@jhmi.edu . The course is online at:
http://oac.med.jhmi.edu/humane_site
Boatman Receives White House Career Award -- On May 4, Dana Boatman, PhD, CCC-A, associate professor of neurology and otolaryngology, received a Presidential Early Career Award in Science and Engineering (PECASE). Nominated for the award by the National Institutes of Health, Boatman was recognized for her "outstanding accomplishments in the field of clinical auditory neuroscience, including pioneering research … [on] the organization of complex sound processing in the human temporal lobe," according to a citation read by John Marburger III, PhD, director of the White House's Office of Science and Technology Policy at the award ceremony.
http://www.ostp.gov/html/PECASErelease5-4-04.pdf
http://grants.nih.gov/grants/policy/pecase.htm
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--JHMI--
