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:
+ Combining Screens Reveals New Tricks of Old Genes
+ Crowding Stem Cells' Personal Space Directs Their Future
+ New Method Makes Building Tons of Drug-Like Peptides Practical
NEWS BRIEFS:
Chakravarti Remembers Genetic Pioneer C.C. Li
Semiannual Animal Research Inspections Set for May 3-14
CAAT Director Goldberg To Give Special Lecture May 5
Utah's Capecchi To Give Annual Daniel Nathans Lecture May 6
Walser Book, "Coping with Kidney Disease," Available
New Instructions for Grants, Protocols With Animal Research
AWARDS AND HONORS:
Huganir and Griffin Elected to NAS
Pandey Named 2004 Beckman Young Investigator
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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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4/1/04
Combining Screens Reveals New Tricks of Old Genes
Johns Hopkins scientists have successfully used new techniques to search the yeast genome for genes that help keep copied chromosomes together, protecting the integrity of the organism's genetic material during cell division.
By combining results from two genome-wide screens, the researchers were able to narrow down the dozens of genes identified by the first screen to just 17 that made both cut-offs, they report in the April issue of Molecular Biology of the Cell.
"By overlapping information from two screens, we were able to figure out what Mother Nature was trying to tell us that wasn't too complicated for us to understand," says Forrest Spencer, PhD, associate professor in the McKusick-Nathans Institute of Genetic Medicine.
In a genome-wide screen, postdoctoral fellow Cheryl Warren, PhD, found 26 genes needed for survival in the absence of a gene called ctf4, already known to be involved in keeping "sister" chromosomes together. Then, using a technique she developed, she identified whether loss of each of those 26 caused the genetic material to become scrambled, leaving just 17 genes.
Fifteen of the highlighted genes were already known to help ensure the accuracy of copied DNA and two help move chromosomes to opposite ends of the dividing cell. But the researchers' results give these "old" genes new jobs, associating them with cohesion, the little-understood process of keeping a chromosome and its copy together until the cell is ready to split in two.
http://www.hopkinsmedicine.org/Press_releases/2004/04_22_04.html
Mol Biol Cell 2004;15(4):1724-1735
http://www.molbiolcell.org/cgi/content/full/15/4/1724
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4/12/04
Crowding Stem Cells' Personal Space Directs Their Future
Johns Hopkins scientists report that restricting the shape and personal space of human stem cells from bone marrow is more important than any known molecular signal in determining the cell type they become.
Understanding the signals that tell stem cells what type of cell to become, and then harnessing those cues to get a single desired cell type, is key to any effort to use these or more primitive embryonic stem cells to regenerate or repair damaged tissue.
In April's Developmental Cell, the Hopkins researchers report that mesenchymal stem cells forced to be spherical efficiently transform into precursors to fat cells, while those allowed to stretch and flatten move closer to becoming bone cells. These stem cells can naturally become fat cells, cartilage, bone cells, or smooth, cardiac or skeletal muscle.
"We found that shape can actually induce molecular signals known to encourage fat cell or bone cell development and causes complete, uniform differentiation," says Christopher Chen, MD, PhD, assistant professor of biomedical engineering.
To understand how cells' shape affected differentiation, MD/PhD candidate Rowena McBeath used a special technique called micropatterning, developed in Chen's lab, to restrict individual cells to small spaces without requiring cellular neighbors to do the crowding. She also discovered that molecular signals RhoA and ROCK, or RhoA kinase, could mimic the effect of shape.
On April 8, McBeath received the Nupur Dinesh Thekdi Research Award for this work as part of Hopkins' 27th annual Young Investigators' Day.
http://www.hopkinsmedicine.org/Press_releases/2004/04_16_04.html
Developmental Cell April 2004;6(4):483-495
http://www.developmentalcell.com/content/article/fulltext?uid=PIIS1534580704000759
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4/19/04
New Method Makes Building Tons of Drug-Like Peptides Practical
Two Johns Hopkins scientists have figured out a simple way to make millions upon millions of drug-like peptides quickly and efficiently, overcoming a major hurdle to creating and screening huge "libraries" of these super-short proteins for use in drug development.
"Our work dramatically increases the complexity of peptide libraries that can be created and the speed with which they can be made and processed," says postdoctoral fellow Chuck Merryman, PhD, who developed the new technique. "In an afternoon, we'll be able to make literally millions of millions of different peptides with medicinal potential."
Peptides act as important messengers and hormones in the body. But because their building blocks, called amino acids, are quickly recycled, peptides made from the 20 naturally occurring amino acids don't last long enough to be useful as medicines. However, adding a tiny methyl group to each amino acid gives the resulting peptide "drug-like" stability.
Writing in the April 19 issue of Chemistry & Biology, the Hopkins scientists reveal that using a simple chemical reaction, reported in the early 1980s, allows them to convert en masse the naturally occurring amino acids to ones that form more stable peptides. The tricky part, Merryman says, was figuring out how to do the conversion while the amino acids were attached to transfer RNA, a carrier molecule required for the biological production of peptides.
Merryman and mentor Rachel Green, PhD, have a patent on the synthetic process under review at the U.S. Patent and Trademark Office.
http://www.hopkinsmedicine.org/Press_releases/2004/04_22b_04.html
Chem & Biol April 2004;11(4):575-582
http://www.chembiol.com/content/article/abstract?uid=PIIS1074552104000857
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Chakravarti Remembers Genetics Pioneer C.C. Li -- Aravinda Chakravarti, PhD, director of Hopkins' McKusick-Nathans Institute of Genetic Medicine, authored a remembrance of geneticist Ching Chun Li for the May 2004 issue of the American Journal of Human Genetics. He writes: "I do not wish to write this remembrance as simply an account of all of C.C. Li's scientific accomplishments but rather as praise of my hero in genetics. I wish to convince you that he should be yours as well." Read it at:
http://www.journals.uchicago.edu/AJHG/journal/issues/v74n5/41124/41124.html
AJHG May 2004;74(5):789-792
Semiannual Animal Research Inspections Set for May 3-14 -- The Johns Hopkins Institutional Animal Care and Use Committee will conduct semiannual inspections of all animal care and use areas at all of Hopkins campuses from May 3-14. An inspection schedule will be sent to investigators by email next week. Investigators using animals in research or teaching are expected to have a knowledgeable person available to answer inspectors' questions and should contact Trish Matos at pmatos1@jhmi.edu or 443-287-3738 if they are scheduled to be away during the inspection period. For institutional guidelines on the care and use of animals in research and for a schedule of training seminars, visit http://www.jhu.edu/animalcare .
CAAT Director Goldberg To Give Special Lecture May 5 -- Alan Goldberg, PhD, professor of toxicology and director of the Center for Alternatives to Animal Testing at the Bloomberg School of Public Health will give a special lecture, "Animals and Alternatives: Societal Expectations and Scientific Need," for graduate students and postdoctoral fellows starting at 4 pm, Wed., May 5, in the West Lecture Hall of the Wood Basic Science Building. For more information contact Sabrina Welborn at swelbor1@jhmi.edu or 410-502-2804. The lecture is hosted by the Professional Development Office.
Utah's Capecchi To Give Annual Daniel Nathans Lecture May 6 -- Mario Capecchi, PhD, co-chairman of the department of human genetics at the University of Utah School of Medicine, will give the Fourth Annual Daniel Nathans, MD, Lecture at 4 pm, May 6, in the Wood Basic Science Auditorium. His talk, "Gene Targeting into the 21st Century: Mouse Models of Human Disease from Cancer to Neuropsychiatric Disorders," will follow a tea that begins at 3:30 pm.
Walser Book, "Coping with Kidney Disease," Available -- John Wiley & Sons has published "Coping with Kidney Disease: A 12-Step Treatment Program to Help You Avoid Dialysis," a book written by Mackenzie Walser, MD, professor of pharmacology and molecular sciences and of medicine at Hopkins, and Betsy Thorpe. A clinical researcher who for decades has looked for ways to avoid or defer dialysis for patients with kidney disease, Walser says the key is to recognize kidney disease early and then try to slow its progression to the end stage. Successful techniques that he developed and described in peer-reviewed journals, and which are included in the book, include adopting a low protein diet, supplemented with amino acids or ketoacids, or ketoconazole, which Walser has shown slows progression of renal failure.
http://www.wiley.com/WileyCDA/WileyTitle/productCd-0471274232.html
New Instructions for Grants, Protocols With Animal Research -- Public Health Service policy requires institutions to verify that approved animal research protocols are identical to relevant components of grant applications. With "Just In Time," this verification occurs prior to award rather than prior to peer review of the grant itself. If the grant's priority score is in a fundable range, the investigator should compare procedures proposed in the grant to related approved protocols. To avoid delays in funding, any necessary new protocols or amendments should be submitted to the Animal Care and Use Committee as soon as possible. Once an award is to be made, School of Medicine investigators will submit grant sections D (design and methods) and F (vertebrate animals) to the ACUC Training and Compliance staff for comparison to approved protocols and amendments. For instructions for investigators in other schools, see:
http://www.jhu.edu/animalcare/training_procedures_congruence.html
Huganir and Griffin Elected to NAS -- Richard Huganir, PhD, and Diane Griffin, MD, PhD, were elected to membership in the National Academy of Sciences on Tuesday, April 20, at the organization's 141st annual meeting in Washington, DC. Huganir, professor of neuroscience and a Howard Hughes Medical Institute investigator at the School of Medicine, and Griffin, professor and chair of the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Bloomberg School of Public Health, join 15 other Johns Hopkins faculty members currently in the Academy.
http://www.hopkinsmedicine.org/Press_releases/2004/04_20_04.html
Pandey Named 2004 Beckman Young Investigator -- Akhilesh Pandey, PhD, assistant professor in the McKusick-Nathans Institute of Genetic Medicine, was named one of this year's Beckman Young Investigators by the Arnold and Mabel Beckman Foundation. Pandey's project is "A Combined Proteomic and Bioinformatic Approach to Study EGF Receptor Signal Transduction Pathway." The Beckman Young Investigators program is intended to provide research support to the most promising young faculty members in the early stages of academic careers in the chemical and life sciences. Last year, faculty members Douglas Robinson, PhD, in cell biology, and Kevin Yarema, PhD, in biomedical engineering, were recipients. Applications for next year are due Oct. 1, 2004.
http://pandeylab.bs.jhmi.edu/
http://www.beckman-foundation.com/byi.html (for other recipients)
http://www.beckman-foundation.com/byiguide.html (for application instructions)
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