Chemical biology

Controlling protein activity with a small molecule–dependent intein

A primary goal of chemical genetics is to discover a small-molecule partner for every protein, capable of modulating its activity. As an alternative to extensive small-molecule synthesis and screening, Yuen et al. developed a genetic strategy to control protein function using a 4-hydroxytamoxifen–dependent, intein-based molecular switch. This molecular switch is particularly attractive for investigating cell-signaling pathways.

Yuen, C.M. et al. J. Am. Chem. Soc. 128, 8939–8946 (2006).

Chromatin techniques

Measuring accessibility of chromosomal DNA on a second time scale

The mechanism by which proteins find access to DNA packaged in chromatin is a long standing question in the field. Bucceri et al. now have harnessed the light-dependent DNA repair enzyme, photolyase, to monitor the accessibility of specific DNA loci in live cells and at high resolution.

Bucceri, A. et al. EMBO J.; published online 15 June 2006.

Imaging and visualization

A fluorescent nitric-oxide sensor for imaging in live cells

Nitric oxide (NO) is an important cell signaling messenger, but its direct detection in vivo has been extremely difficult. Lim et al. now present a sensor consisting of a copper and fluorescein complex, which upon reaction with NO results in fluorescence, making possible the direct imaging of NO in live cells.

Lim, M.H. et al. Nat. Chem. Biol. 2, 375–380 (2006).

Cell biology

Tumor expression profiling with immuno-LCM

Buckanovich et al. present a method combining immunohistochemistry and laser-capture microdissection (immuno-LCM) to purify distinct cell populations from complex tissue samples. They used this tool to carefully isolate specific cell populations from tumor microenvironments to facilitate analysis of the underlying molecular events by RNA expression profiling.

Buckanovich, R.J. et al. Cancer Biol. Ther.; published online 9 June 2006.

Microscopy

Probing cell-surface glycans with atomic force microscopy

There is great general interest from the glycobiology community in new methods for investigating glycan modifications on cell-surface proteins. Using lectins as probes, Lekka et al. used atomic force microscopy to interrogate both the identity of the oligosaccharides as well as their relative densities on the surfaces of living cells.

Lekka, M. et al. Chem. Biol. 13, 505–512 (2006).