Mutagenesis

A better knockout mouse

Inducible gene targeting in mice is time-consuming and can be unreliable. Zeng et al. now describe an improved conditional and reversible tetracycline-based system called iKO to generate knockout mice. It boasts more tightly regulated expression of the gene of interest, powered by the gene's own promoter, so there is no need to worry about leakage or tissue specificity. This should be especially welcome news to the mouse community.

Zeng, H. et al. PloS Genet. 4, e1000069 (2008).

Nanotechnology

Nanoparticle design

It can be quite a challenge to get nanoparticle-based delivery vehicles carrying cytosol-bound cargo through the cell membrane without doing any damage. Verma et al. now demonstrate that gold nanoparticles covered in alternating negatively charged and hydrophobic groups are safely delivered, whereas nanoparticles with these groups randomly distributed get stuck in endosomes. These findings are expected to be especially helpful to researchers designing gene and small interfering RNA–based therapies.

Verma, A. et al. Nat. Mater., published online 25 May 2008.

Genomics

Resequencing by hybridization

Competition between next-generation sequencing technologies continues to heat up. Pihlak et al. describe the implementation of a sequencing-by-hybridization (SBH) approach, called shotgun SBH, that solves problems of previous SBH implementations. The genomic sample is cut into fragments, immobilized on a glass surface by rolling-circle amplification and probed sequentially with universal oligonucleotides. The high throughput and low cost of the method is appealing for simple resequencing applications.

Pihlak, A. et al. Nat. Biotechnol. 26, 676–684 (2008).

Microscopy

Large-scale 3D subdiffraction imaging

Many methods have been described for subdiffraction fluorescence imaging. One implementation, structured illumination microscopy (SIM), involves illumination with multiple interfering beams of structured light to double the resolution of a conventional microscope. Gustafsson et al. now extend SIM to imaging in three dimensions and Schermelleh et al. apply multicolor three-dimensional SIM to investigate the structure of the mammalian nucleus.

Gustafsson, M.G. et al. Biophys. J. 94, 4957–4970 (2008).

Schermelleh, L. et al. Science 320, 1332–1336 (2008).

Genomics

Fruit fly CNP map

It has long been suspected that copy-number changes could be influenced by natural selection. Emerson et al. now present evidence of just that. Using Affymetrix genomic tiling arrays, they generated a high-resolution copy-number polymorphism map for the fruit fly. They discovered that several toxin-related genes are duplicated including the cytochrome P450 gene Cyp6g1, critical in conferring resistance to the insecticide dichloro-diphenyl-trichloroethane, DDT.

Emerson, J.J. et al. Science, published online 5 June 2008.