Stem cells

Mice from iPSCs

Two groups show that mouse induced pluripotent stem cells (iPSCs) can generate fertile adult mice in tetraploid complementation assays, in which all tissues are derived from the pluripotent cells. Failure to achieve this so far has raised questions about the pluripotency of iPSCs, but these results show that full pluripotency via reprogramming is possible. The mice will be useful models to study the function of cells and tissues that are entirely iPSC-derived.

Boland, M.J. et al. Nature 461, 91–94 (2009).

Zhao, X.Y. et al. Nature 461, 86–90 (2009).

Proteomics

Mammalian tethered catalysis

The tethered catalysis method, originally developed in yeast, is used to identify post-translational modification–specific binding proteins (PTMBPs). A substrate peptide is tethered to an enzyme that post-translationally modifies the peptide, which then serves as bait for PTMBPs. The PTMBPs can be identified by affinity purification and mass spectrometry. Spektor and Rice now report an expansion of the tethered catalysis approach for application in mammalian cells.

Spektor, T.M. & Rice, J.C. Proc. Natl. Acad. Sci. USA 106, 14808–14813 (2009).

Chemical tools

Cleavable linkers for affinity chromatography

Biotin-streptavidin–based affinity chromatography is widely used for identifying protein-protein and protein-ligand interactions. However, releasing the biotinylated target protein from the streptavidin support is a harsh and inefficient process. Park et al. now report an acylhydrazone-based linker that can be incorporated into a biotin tag, and which is cleaved under mildly acidic conditions. This allows for a clean release of the target protein without requiring denaturation, facilitating downstream analysis.

Park, K.D. et al. Chem. Biol. 16, 763–772 (2009).

Genomics

Predicting copy-number variation

Though duplicated regions of the human genome are the culprits of various conditions ranging from color-blindness to lupus, these regions have been very difficult to study. Alkan et al. describe an algorithm called mrFAST, which can predict absolute copy-number variation in duplicated genome segments from next-generation sequencing data. By examining three human genomes, Alkan et al. estimated that 73–87 genes vary in copy number between individuals.

Alkan, C. et al. Nat. Genet. advance online publication (30 August 2009).

Drug discovery

Mapping drug space

Drugs that target pathogenic bacteria or cancer cells can potentially also interfere with human enzyme function. Thus, an understanding of how drugs can affect metabolism is very important. Adams et al. present an online resource of interactive maps of potential drug action in metabolism, which compares the chemical structural similarities of drugs and human metabolites. The resource contains information on 246 drug classes and 385 organisms; such maps could be used to design more effective drugs.

Adams, J.C. et al. PLoS Comput. Biol. 5, e1000474.