Proteomics

Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components

Peterson et al. describe a biochemical alternative to the widely used genetic suppressor screen. Cells treated with a small-molecule inhibitor are incubated with concentrated cytosolic fractions from untreated cells; closer analysis of the fractions that reverse the inhibitor phenotype can reveal drug targets—including multiprotein complexes—and proteins that act downstream of these targets.

Peterson, J.R. et al. Chem. Biol. 13, 443–452 (2006).

Gene Regulation

Preventing gene silencing with human replicators

Transcriptional silencing presents a serious obstacle to the efficacy and safety of insertion-based gene therapy. Previous research has shown that transcriptionally active chromosomal regions tend to undergo replication early in S phase, and Fu et al. demonstrate that the extent of silencing can be greatly reduced by the incorporation of active replicator sequences into transgenes.

Fu, H. et al. Nat. Biotechnol 24, 572–576 (2006).

Imaging And Visualization

Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps

Analyzing the development of complex tissues often requires the ability to distinguish between similar but distinct cell populations. As a tool for such mapping projects, Farago et al. have developed a indicator system that allows them to visually differentiate cells that simultaneously express two genes of interest from cells where only one of the two is being expressed.

Farago, A.F. et al. Neuron 50, 205–218 (2006).

Microfluidics

Microfabricated bioprocessor for integrated nanoliter-scale Sanger DNA sequencing

Whereas some scientists foresee the impending demise of Sanger sequencing, Blazej et al. still see advantages in this venerable technique. They describe a microfabricated lab-on-a-chip system capable of accurate Sanger sequencing from one femtomole of template DNA and discuss the possibility of developing similar nanoscale bioprocessors for other genomic applications.

Blazej, R.G. et al. Proc. Natl. Acad. Sci. USA 103, 7240–7245 (2006).

Microscopy

STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis

Stimulated emission depletion (STED) considerably improves the resolution of fluorescence microscopy, allowing the visualization of objects tens of nanometers in diameter with a minimum of effort by the investigator. Willig et al. demonstrate the power of STED microscopy, imaging the clustering of synaptic vesicles at the presynaptic membranes of rat neurons.

Willig, K.I et al. Nature 440, 935–939 (2006).