Model organisms

Zinc-finger nucleases for gene correction in vivo

There a great deal of interest in the use of zinc-finger nucleases for tailored genome engineering, but they have not yet been used for genome modification in vivo. Li et al. now use zinc-finger nuclease–mediated targeting of a promoter-less DNA fragment to correct mutations in a mouse model of hemophilia B. They intraperitoneally injected a hepatotropic adeno-associated viral vector to deliver the nuclease and the therapeutic fragment, and observed sufficiently effective gene targeting to restore functional clotting in the mouse.

Li, H. et al. Nature advance online publication (26 June 2011).

Mass spectrometry

Introducing the Q Exactive

Michalski et al. introduce the Q Exactive, a benchtop mass spectrometer with many beneficial advantages for proteomics research. This instrument combines quadrupole and Orbitrap analyzers, allowing multiplexed operation for single-stage and tandem mass spectrometry. Compared to current top-of-the-line Orbitrap instruments, the Q Exactive also offers high mass spectrometric resolution, identifies more peptides in a single run and is faster and easier to use.

Michalski, A. et al. Mol. Cell. Proteomics advance online publication (3 June 2011).

Structural biology

Combined solution and solid-state NMR spectroscopy

Bertini et al. report a method for investigating the structure of large proteins by nuclear magnetic resonance (NMR) spectroscopy both in solution and in solid state without changing the sample tube. They first performed solution-state NMR measurements on the protein apoferritin. Then, by spinning the sample tube at ultracentrifugation speeds, the protein sedimented on the tube walls, allowing them to make solid-state measurements. The method is applicable to proteins larger than about 100 kilodaltons.

Bertini, I. et al. Proc. Natl. Acad. Sci. USA 108, 10396–10399 (2011).

Molecular enginering

A minimalist nuclear pore

Disordered Phe-Gly domains of nucleporins are thought to constitute the selectivity filter at the nuclear pore. Kowalczyk et al. report a biomimetic nuclear pore complex capable of selective protein transport. The minimalist structure consisted of a silicon-based nanopore coated with nucleoporin Phe-Gly domains. Stringency of selectivity depended both on nanopore diameter and the nucleoporin of choice, revealing intrinsic differences between nucleoporin function at the selectivity barrier.

Kowalczyk, S.W. et al. Nat. Nanotechnol. 6, 433–438 (2011).

Imaging

Fluorescent cell biolasers

Lasers emit light through optical amplification of input electromagnetic energy. This is achieved through stimulated photon emission by an appropriate “gain medium” inside a highly reflective optical resonator. By pumping single fluorescent cells with brief optical pulses in a mirrored biconcave microcavity, Gather and Yun could stimulate the emission of bright directional laser beams without affecting cell viability. The concept could enable new techniques for cellular and tissue imaging.

Gather, M.C. & Yun, S.H. Nat. Photonics 5, 406–410 (2011).