Systems biology

Metabolic network in 3D

Zhang et al. used structural genomics to solve three-dimensional structures of the 478 proteins (120 by experiment and 358 by modeling) involved in the central metabolic network of the bacterium Thermotoga maritima. This comprehensive structural analysis allowed them to assign metabolic functions to the proteins and identify essential genes as well as investigate questions about the mechanism of metabolic network expansion and the evolution of protein folds.

Zhang, Y. et al. Science 325, 1544–1549 (2009).

Stem cells

Reprogramming with OCT4

Four transcription factors, OCT4, SOX2, c-Myc and KLF4, are necessary to reprogram somatic cells into induced pluripotent stem (iPS) cells. But for clinical applications involving iPS cells, it is desirable to avoid overexpressing the oncogenes encoding c-Myc and KLF4. Now Kim et al. report that OCT4 (POU5F1) alone is all you need to reprogram human neural stem cells into neural iPS cells that look like and behave like human embryonic stem cells.

Kim, J.B. et al. Nature 461, 649–653 (2009).

Chemical biology

Inducing cell signaling

Hashiro et al. describe an alternative concept for inducing specific cell-signaling pathways, without requiring protein engineering: they take advantage of the fact that many proteins activate downstream signaling pathways upon localizing to the plasma membrane. By placing a synthetic ligand at the plasma membrane, they can induce translocation of the endogenous protein to the plasma membrane and subsequent activation of the downstream signaling cascade.

Hashiro, S. et al. J. Am. Chem. Soc. 131, 13568–13569 (2009).

Proteomics

Natural product discovery using proteomics

Nonribosomal peptide synthetases and polyketide synthetases are very large enzyme machines in microorganisms that synthesize interesting and potentially pharmacologically valuable metabolites. Bumpus et al. describe an assay to enrich for such high-molecular-weight proteins, identify them by mass spectrometry and use the sequence information to link gene expression to the metabolic product.

Bumpus, S.B. et al. Nat. Biotechnol. 27, 951–956 (2009).

Genomics

Metagenomics of bug splatter

With a unique approach to sampling the diversity of species in a local environment, Kosakovsky Pond et al. collected biological matter (from insects, bacteria and other species) from the front bumper of a moving vehicle and subjected it to phylogenetic profiling. They built a complete pipeline for metagenomic analysis, which involved DNA sequencing of the bumper samples, quality control, sequence alignment via database matching and taxonomic assignment; all tools are available in the Galaxy platform.

Kosakovsky Pond, S. et al. Genome Res. advance online publication (9 October 2009).