Scientists can diagnose genetic disorders such as Down's syndrome by using gene markers, or "probes", which bind to only highly similar chains of DNA. Once bound, the probe's location can be easily detected by fluorescence, and this gives information about the gene problem.
Detecting these probes is often a slow and difficult process, however, as the chains become tightly coiled. The new method presented by Kyohei Terao from Kyoto University, and colleagues from The University of Tokyo, uses micron-sized hooks controlled by lasers to catch and straighten a DNA strand with excellent precision and care.
"When a DNA molecule is manipulated and straightened by microhooks and bobbins, the gene location can be determined easily with high-spatial resolution," says Terao.
The team used optical tweezers - tightly focused laser beams - to control the Z-shaped micro hook and pick up a single DNA "thread". The hook is barbed like an arrow, so the thread can't escape. When caught on the hook, the DNA can be accurately moved around by refocusing the lasers to new positions.
But just like thread in a sewing machine, a long DNA chain can be unwieldy - so the researchers built micro "bobbins" to wind the chain around. The lasers move one bobbin around another, winding the DNA thread onto a manageable spindle.
It is "an excellent idea to fabricate unique microtools that enables us to manipulate a single giant DNA molecule", says Yoshinobu Baba, who researches biologically useful microdevices at Nagoya University, Japan. The technology will also be useful for a number of other applications including DNA sequencing and molecular electronics, he adds.
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Because the protective effect of HDAC inhibitors may occur even after the initial blockage of blood flow, therapies based on Gruber's research may lead to an emergency treatment following a heart attack. In addition, because open-heart surgery for both children and adults requires a period in which the heart is stopped, such treatment might also protect tissues from the adverse effects of interrupting blood flow during surgery.
For now, said Gruber, the next step for his study team will be to test how HDAC inhibitors work in protecting against ischemic injury in larger animals.
A National Institutes of Health grant partially supported the research, in addition to funding from the McCabe Foundation, the University Research Foundation and the Division of Pediatric Cardiothoracic Surgery at The Children's Hospital of Philadelphia.
Gruber's co-authors were Anne Granger, Ibrahim Abdullah, Faith Huebner, and Thomas Huebner, of Children's Hospital; and Jonathan A. Epstein, M.D., of the University of Pennsylvania School of Medicine. Gruber, Granger, and co-authors Andrea Stout and Tao Wang are members of the Penn Cardiovascular Institute, of which Epstein is the scientific director.
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