Stem cells

p53 knockout rats

Transgenic technologies for rats have lagged behind those developed for mice. Tong et al. now describe the generation of p53 (Tp53) knockout rats. They disrupted the p53 gene in germline-competent rat embryonic stem cells via homologous recombination and then introduced the cells into early-stage embryos to generate the knockout rat. This technology will permit the creation of a variety of gene-knockout rat strains for studying human disease.

Tong, C. et al. Nature 467, 211–213 (2010).

Proteomics

The aggregating proteome

Protein aggregation occurs in neurodegenerative disorders such as Alzheimer's and Huntington's disease, but little is known about age-related protein aggregation in the absence of disease. David et al. performed a systematic proteomics analysis to address this question, using quantitative mass spectrometry to compare the insoluble fraction of proteins left after extracting all soluble proteins in young versus old roundworms. They found that hundreds of proteins become more insoluble in aging worms.

David, D.C. et al. PLoS Biol. 8, e1000450 (2010).

Signal transduction

An integrated view of GPCR signaling

G protein–coupled receptor (GPCR) signaling is typically measured by quantifying second messengers via fluorescence, but such assays do not reveal the integrated cellular response. Schröder et al. now demonstrate that a label-free, polarized light–based technology to monitor the dynamic mass redistribution (DMR) of molecules in the cell can be used to obtain a more complete view of GPCR signaling. This DMR assay allowed them to probe complex signaling patterns and map them to individual G-protein pathways.

Schröder, R. et al. Nat. Biotechnol. 28, 943–949 (2010).

Lab on a chip

Multiplexing in the billions

In high-throughput suspension bioassays, a barcoding system is necessary for keeping track of different analytes. This can be done by attaching the analyte to a microparticle that is either spectroscopically encoded (by color) or graphically encoded (by pattern). Lee et al. now report a method combining spectroscopic and graphical encoding to generate potentially billions of unique magnetic microparticles carrying up to ten spatially separate colored barcodes, which can be decoded by ordinary microscopes.

Lee, H. et al. Nat. Mater. 9, 745–749 (2010).

Biophysics

Scanning ultrafast electron microscopy

Scanning electron microscopy (SEM) can be used to obtain three-dimensional–like images of surfaces. Ultrafast electron microscopy allows imaging in both space and time at very high resolution. Yang et al. now combine these modalties to develop scanning ultrafast electron microscopy (SUEM), a four-dimensional imaging technique with nanometer and sub-picosecond spatiotemporal resolution. They show that SUEM can be used to rapidly obtain three-dimensional pictures of biological specimens, including an ant's setae and an erythrocyte.

Yang, D.-S. et al. Proc. Natl. Acad. Sci. USA 107, 14993–14998 (2010).