Volume 8 Issue 8, August 2011

A million picoliter PCR chambers give quick, precise answers.

Two structure-driven studies of the culprits behind diseases associated with amyloid fibers give clues to stopping these agents in their tracks.

Expression of a microRNA cluster predicts whether or not a particular human pluripotent stem cell line will differentiate well into neurons.

Researchers produce a mouse embryonic stem cell library along with convenient vectors.

A next-generation sequencing instrument allows deep quantitative measurement of protein-DNA binding affinity.

Antibodies targeting short sequence motifs found in multiple proteins can be used in a discovery array–based platform.

Molecularly imprinted polymers act as 'smart' nucleants for protein crystallization.

Researchers use large libraries, focused libraries and rational design to engineer useful proteins.

Automated methods can now extract brain-image coordinates appearing in hundreds of publications in targeted topic areas and then integrate these data to form computational models that classify new brain-image data.

The two-color traffic light reporter reads out what pathway is used to repair a DNA break and will increase insights into genome engineering.

An absolute quantification approach combined with differential affinity capture provides a means by which to accurately measure distinct pools of ubiquitin in cells or tissues.

Long before mass spectrometry became an important tool for cell biology, it was yielding scientific insights in physics and chemistry. Here is a brief history of how the technology has expanded from a tool for studying atomic structure and characterizing small molecules to its current incarnation as the most powerful technique for analyzing proteomes.

Bioorthogonal chemistry allows a wide variety of biomolecules to be specifically labeled and probed in living cells and whole organisms. Here we discuss the history of bioorthogonal reactions and some of the most interesting and important advances in the field.

A diverse array of small molecule–based fluorescent probes is available for many different types of biological experiments. Here we examine the history of these probes and discuss some of the most interesting applications.

This digital PCR device arrays samples into one million small-volume reactors, achieving a dynamic range of 10⁷, measurement precision better than 1% and the ability to detect single-nucleotide variants present at less than 1:100,000.

This algorithm uses the soft-clipped, unaligned parts of a sequence read to map structural variation in cancer genomes with high predictive accuracy.

Quantitative, large-scale in vivo phosphoproteomics analyses are made possible with a form of spike-in stable-isotope labeling with amino acids in cell culture (SILAC), in which SILAC-labeled cell lines act as an internal standard for mass spectrometry–based tissue phosphoproteome analysis.

Two sequence-verified, clonal, publicly available collections of human open reading frames are reported. One collection is in a lentiviral vector for expression in mammalian cells; the other is in the Gateway vector system.

A new method called functional ultrasound (fUS) is reported that allows imaging of transient changes in blood volume in the whole rat brain with a spatiotemporal resolution not attained by other functional brain imaging modalities.

A framework and web interface for the large-scale and automated synthesis of human neuroimaging data extracted from the literature is presented. It is used to generate a large database of mappings between neural and cognitive states and to address long-standing inferential problems in the neuroimaging literature.

A fluorescent reporter, named traffic light, reads out whether repair of a DNA break occurs by nonhomologous end-joining or by homologous recombination. It should enable the identification of factors that affect repair pathway choice and thus improved approaches for genome engineering.

The functional role of protein phosphorylation is determined not just by whether a particular site is phosphorylated or not but also by the site's stoichiometry. A method to determine the absolute stoichiometries of protein phosphorylation on a proteomic scale is described.

Membrane protein interactions and conformational changes can be sensitively monitored with two-photon polarization microscopy, a method that takes advantage of the anisotropic absorption properties of fluorescent proteins. The authors applied the method to image G-protein activation and changes in intracellular calcium concentration.

Ubiquitin, an important post-translational modification that regulates a variety of biological processes is found in free and conjugated (monoubiquitin and polyubiquitin) forms in the cell. A method for precisely measuring these cellular pools using protein standard absolute quantification mass spectrometry is described; the approach should yield insights into ubiquitin signaling.

We celebrate the 2011 International Year of Chemistry by highlighting the important contributions of chemistry to methods currently used in biology research. In a series of Commentaries, developers of chemistry-related tools and methods in three selected areas of research discuss their history and applications.