Stem cell burnout blamed on tumor suppressor gene
A gene known for halting cell growth and preventing tumor formation causes stem cells to lose their regenerative capacity in aging mice, according to three papers published in the online edition of Nature Wednesday. Together they suggest that inhibiting this gene might prolong the life of stem cells, promote tissue repair, and delay aging.
Diminishing stem cell numbers and activity with age leads to less tissue renewal and repair, but researchers didn’t know just how the cells grew old. In one of the reports, David Scadden and colleagues at the Harvard Stem Cell Institute and Massachusetts General Hospital show that the decreased ability of bone marrow stem cells to produce new blood cells in adult mice coincides with an increased production of a protein called p16INK4a. When the researchers knocked out the p16INK4a gene, grown mice maintained a youthful stem cell population in their bone marrow.
The accumulation of p16INK4a over time affected other stem cells too. A second paper showed that the protein slowed regeneration of the insulin-producing beta cells of the pancreas in aging mice. This declining population of cells might contribute to adult-onset diabetes, write the authors, who include Keith Ligon from Brigham and Women’s Hospital and Angela Koh and Susan Bonner-Weir at the Joslin Diabetes Center. A third group found that p16INK4a played the same role in neuronal stem cells in the brain.
There was one hitch: although mice lacking p16INK4a had spry stem cells, they also got more tumors. Mother Nature apparently has good reason to limit the growth of stem cells, whose uncontrolled growth could lead to tumors.
Getting molecules into shape
If you have ever tried to put a left shoe on your right foot, you understand the chemist’s struggle with enantiomers—pairs of molecules that are mirror images of each other and are not superimposable. When it comes to biological activity, only one of the two molecules interacts properly with a particular protein target. In drug development, this difference can be critical: often, one isomer is helpful as a drug, and the other is harmful. The challenge for chemists is to prepare large amounts of just one type of isomer. Most chemical reactions tend to produce both.
Now, Amir Hoveyda and Mark Snapper of Boston College are addressing the problem with a new catalyst they’ve developed. The reagent adds silicon ‘protecting’ groups to symmetric precursors, but does it in a specific way to produce almost exclusively one enantiomeric isomer, saving the laborious work of purifying isomers from a mixture.
In one synthetic scheme, the researchers replaced a six-step, multi-day process with a single reaction to produce an enantiomer mix with more than 90 percent of the desired isomer. Fewer steps mean a higher yield and less waste. The catalyst, an amino acid derivative, promises a faster, more environmentally friendly, and cheaper way to produce the building blocks needed for many pharmaceuticals. The reactions do require a large amount of the catalyst, but it is easy to prepare from commercially available precursors, and can be recycled several times.
“This procedure is likely to have a significant impact on the efficiency and cost of construction of single-enantiomer products,” wrote Scott Denmark, a chemistry professor from the University of Illinois, Urbana-Champaign, in an accompanying commentary. The research report appears in this week’s of issue of Nature.
Nanoantenna puts laser light on the spot
By adding a tiny antenna to a commercial diode laser, Harvard University researchers have created a high-resolution laser light source that could one day stuff multiple terabytes of data onto one CD. The nanoantenna technology could also benefit biologists by enabling the production of more powerful microscopes and more precise optical tweezers that could manipulate small molecules.
Diode lasers are common light sources for many applications, ranging from fiber optics to barcode readers and DVD players. Nanoscale applications of diode lasers are limited, however, by the resolution of conventional optics. To solve this problem, the researchers installed an optical antenna on the surface of the diode. The 100-nanometer long antenna, made of a pair of gold nanorods, collects the laser light and concentrates it into an intense spot about 40 nanometers wide, much smaller than the 800-nanometer wavelength of the emitted light. This technology could be the basis for optical microscopes and tweezers whose resolution is not limited by the wavelength of light.
For biologists, who use lasers to sort cells, perform microdissections, and isolate single chromosomes and other large cellular components, the new antenna could take these techniques into the nanorealm. Optical tweezers, which use a focused laser beam to grab particles from 100 nanometers to a few microns in size, have been widely used to study DNA replication and the protein motors that propel organelles and other proteins inside cells. With the new technology, the tweezers could trap even smaller molecules.
The device, developed by Ertugrul Cubuku, Eric Kort, Kenneth Crozier and Federico Capasso of Harvard’s Division of Engineering and Applied Sciences, was described in a paper published last week in Applied Physics Letters.
