Stem cells

From fibroblasts to neurons

No biologist would be surprised these days if one cell type was converted to another by going through a pluripotent stage, nor if this reprogramming was done directly between two closely related cell lineages. But Vierbuchen et al. now demonstrate a way to directly convert fibroblasts into distantly related excitatory neurons. By introducing a specific combination of genes encoding transcription factors (Ascl1, Brn2 and Myt1l) into mouse embryonic and postnatal fibroblasts, they made induced neuronal cells with characteristics and functional properties of mature neurons.

Vierbuchen, T. et al. Nature 463, 1035–1041 (2010).

Systems biology

Validating functional CRMs

Cis-regulatory modules (CRMs) control gene expression as parts of complex regulatory networks. To experimentally validate CRMs, which are often identified based on computational predictions, Nam et al. recently developed a high-throughput assay. The researchers barcoded each CRM that drove expression of a reporter gene, then injected the constructs into a sea urchin embryo and subsequently analyzed the isolated mRNA by quantitative PCR. This approach will be a valuable tool for regulatory systems biology.

Nam, J. et al. Proc. Natl. Acad. Sci. USA 107, 3930–3935 (2010).

Protein biochemistry

Routine NMR structures of large proteins

It is challenging to solve the structures of large proteins by nuclear magnetic resonance (NMR) spectroscopy without resorting to deuterium labeling. Raman et al. show that protein structures of up to 25 kilodaltons can be solved via NMR spectroscopy by using sparse information about backbone chemical shifts and residual dipolar couplings. The researchers used these data to guide Rosetta-based structural modeling of several proteins with known and novel structures.

Raman, S. et al. Science 327, 1014–1018 (2010).

Neuroscience

Recording the flying brain

An ideal way to understand how the nervous system transforms sensory information into locomotor actions is by directly recording the activity of relevant neurons in animals that are receiving the stimulus while they are free to move. Maimon et al. developed a way to perform whole-cell patch-clamp recordings from genetically identified neurons in Drosophila melanogaster in flight, allowing them to study the activity of a class of visual neurons and monitor optomotor responses in the tethered, flying flies.

Maimon, G. et al. Nat. Neurosci. 13, 393–399 (2010).

Synthetic biology

Designer promoters

The ability to tune the amounts of genes expressed in different cell types would permit more precise reverse genetic experiments. Schlabach et al. isolated strong synthetic enhancers by screening a library of 100-mer sequences consisting of tandem repeats of all possible 10-mers. Reporter expression varied in different cell lines and could be additionally modulated by screening for synergistic effects between enhancers.

Schlabach, M.R. et al. Proc. Natl. Acad. Sci. USA 107, 2538–2543 (2010).