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JHM Science e-Newsletter Vol. 6, No. 4, August 1, 2006

A once-a-month electronic newsletter for basic, preclinical and translational
research news from the Johns Hopkins School of Medicine. Please forward
freely. Browse back issues of the e-Newsletter in the archive.
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RESEARCH HIGHLIGHTS:

NEWS BRIEFS:

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Do you have a manuscript in press? Fax your manuscript or galley proofs to
Media Relations and Public Affairs at 410-614-8951, or e-mail the appropriate
media relations person.

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RESEARCH HIGHLIGHTS:
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7/5/06
Cell Survival Depends on Chromosome Integrity

What do cells need to survive? Basic needs like food, water and protection from injury come to mind. Now, Jef Boeke’s team in the High Throughput Biology Center of the Institute for Basic Biomedical Sciences has discovered proteins critical for keeping chromosomes intact also are critical for cell survival. 

Boeke and colleagues show that removing from yeast cells two proteins called sirtuins – Hst3p and Hst4p – causes cells to become hypersensitive to chemicals and temperature and to spontaneously break and/or lose chromosomes. In humans, the loss or breakage of chromosomes can cause cells to lose control of when and if they are supposed to divide, becoming cancerous. 

Chromosomes in yeast cells missing the sirtuins Hst3p and Hst4p become hyperacetylated on lysine-56. The researchers think lysine-56 acetylation may be a universal mechanism for marking damaged DNA.

Read the news release here.

Read the paper here.
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7/12/06
Scientists Coax Nerve Fibers to Regrow After Spinal Cord Injury

Severed fingers can be reattached and the severed nerves grow new ends to restore function. But the same doesn’t occur when nerves are severed from the spinal cord. Ron Schnaar’s team in pharmacology and neuroscience has discovered a way to coax these severed spinal cord nerves to grow new ends. 

The team looked at the boundary between the spinal cord and the periphery in rats. The spinal cord and central nervous system inhibits nerve regrowth through molecules known as axon regeneration inhibitors, dubbed ARIs. ARIs are not found in the periphery where nerve ends do regrow. The team bathed severed nerves at the spinal cord-periphery boundary with enzymes that destroy ARIs and looked for growth of new nerve ends. 

Rats treated with sialidase showed more than twice the number of new nerve fibers than rats treated with saline. These new nerve fibers sprouted from spinal cord nerves. Schnaar and team now are testing the same treatment to see whether it will help nerve regeneration in other types of spinal cord injuries.

Read the news release here.

Read the paper here.
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7/21/06
Hopkins Researchers Develop New Tool to Watch Real-Time Chemical Activity in Cells

Using glowing proteins from jellyfish, Jin Zhang’s group in pharmacology and molecular sciences has developed a biosensor molecule that can sense the activity of a particular enzyme, PKA, in living cells. The ability to do this in living cells allows researchers to follow enzyme activity in real time and space and cellular environs, all of which potentially could streamline the manufacture of new drugs and therapies.  

The biosensor is based on a technology called FRET, where when two molecules are close enough physically, one can transfer energy to the other. The biosensor contains two parts that glow in different colors, separated by a center portion that can change shape if triggered by the right signal, in this case active PKA. In the absence of PKA, the two ends of the biosensor are far apart and the sensor glows cyan. Active PKA changes the shape of the sensor, bringing the two ends together. The cyan glowing end transfers light energy to the other end, causing it to glow green. Green glowing spots in cells signal the presence of active PKA. 

PKA is short for protein kinase A, a member of a large family of proteins known as kinases, which are implicated widely in diseases and an emerging class of drug targets. The new biosensor can be used in high-throughput screening to identify chemicals that interfere with kinase function and may show promise in drugs for treating disease.

Read the news release here.

Read the paper here.
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7/21/06
Researchers Find Link Between Cell’s Energy Use and Genome Health

While studying how a cell keeps its genetic material intact, Jef Boeke’s group in the High Throughput Biology Center of the Institute for Basic Biomedical Sciences found that one enzyme vital for managing a cell’s energy also controls gene expression. Knocking out this enzyme led the cell to turn off 70 percent of its 5,000 genes and die.

The team found that an enzyme called Asc2p, thought to be involved in metabolizing sugar to energy, actually resides in the nucleus with the chromosomes. It turns out this enzyme is responsible for providing the molecule that controls how tightly chromosomes are packaged. Tightly packed chromosomes are associated with silenced genes. In fact, removing the enzyme Acs2p causes genes to be silenced, suggesting that in its absence, chromosomes remain tightly packed, preventing gene expression.
   
Read the news release here.

Read the paper here.
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NEWS BRIEFS:
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L. Mario Amzel, Ph.D. Named New Chair of Biophysics and Biophysical Chemistry

Amzel, who earned both his bachelor’s and Ph.D. degrees in physical chemistry at Universidad de Buenos Aires, Argentina, has been appointed the new head of the Department of Biophysics and Biophysical Chemistry in the Institute of Basic Biomedical Sciences at The Johns Hopkins University School of Medicine.

Amzel joined Hopkins in 1969 for a postdoctoral fellowship and has remained here ever since, rising to full professorial status in 1984. His early work focused on figuring out the shapes and structures of proteins. Amzel was the first to solve the structure of part of an antibody, the molecule that helps the human immune system fight off infection. He was also part of a team of researchers at Hopkins who produced the first high-resolution pictures of how antibodies interact with antigens, foreign molecules invading the body.

Amzel serves as course director of “Biochemical and Biophysical Principles” and lectures in seven different courses at Hopkins. He was awarded the 1994 Teacher of the Year award from the graduate students at the School of Medicine and the University Alumni Teaching Award in 1999.

Seth Blackshaw, Ph.D. Named to W.M. Keck Foundation 2006 Class of Distinguished Young Scholars in Medical Research

Seth Blackshaw, Ph.D. of the department of neuroscience at Hopkins has developed ways to identify the molecules that determine how the seven different types of cells in the retina become functionally different from one another during embryonic development. By using molecular and genomic approaches, Blackshaw and colleagues are systematically identifying genes that are differentially expressed in each cell type. Identifying and studying the functions of these genes will lead to a better understanding of what goes wrong when some of these cells degenerate, causing loss of vision. His work holds the promise that one day doctors could treat certain types of blindness by regenerating a patient's retinal cells.

Gregg L. Semenza, M.D., Ph.D. Awarded NIH Grant for New Wound Healing Center 

Semenza's group will study how certain types of cells, called endothelial progenitor cells, can speed healing and reduce scarring in burn wounds. The cells, dubbed EPCs, are produced in bone marrow and are essential to rebuilding blood vessels, which are needed to repair injured tissues. The research team will test ways to promote this natural healing by turning on a specific set of genes that recruit EPCs to the wound site.

The grant is part of a new initiative of the National Institutes of Health to bring together experts from many fields including microbiologists, engineers, cell biologists, dermatologists, and other physicians to integrate current knowledge about how wounds heal and generate new strategies to improve treatment.
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