Volume 14 Issue 8, August 2018

Adaptive survival signaling can promote resistance to individual kinase inhibitors. A new study used a pathway-based approach to characterize shared kinome-wide rewiring mechanisms across multiple kinase inhibitors and developed rational drug-combination approaches that target cross-talk between two signaling pathways.

Monitoring MHC-I dynamics upon binding to its chaperone TAPBPR helps us understand how optimal peptide sequences are selected for presentation and coordinated with release of the chaperone from the ternary peptide–MHC-I–TAPBPR complex.

Calcium channels are crucial regulators of a broad range of biological processes. A photoswitchable chemical probe allows the opening and closing of these channels with unprecedented temporal resolution, providing new opportunities to study calcium-dependent signaling pathways in real time.

Synthetic biology is enabling functional metagenomics by providing genetic circuits to identify new pathways that, in turn, facilitate design of new biosensors and synthetic systems.

Three homologous cytochrome P450s from monoterpene indole alkaloid-producing plants enable the identification of sarpagan bridge enzyme, which catalyzes either cyclization or aromatization to yield sarpagan or β-carboline alkaloids, respectively.

A photoswitchable probe to control Ca²⁺ influx through L-type Ca²⁺ channels is useful in pancreatic β cells and can be employed to modulate beating rate in explanted hearts.

Proteomic mapping of dynamic changes in kinase signaling after drug treatment identifies that AURKA inhibition is required for drug sensitivity, representing a new co-targeting opportunity with PI3K, AKT, or mTOR inhibitors in breast cancer.

Potent pan-Atg8 or GABARAP-selective inhibitory peptides derived from giant neuronal ankyrin-B and -G effectively block autophagy in cell cultures and in C. elegans spatiotemporally.

The membrane-bound enzyme CybB can directly oxidize superoxide to molecular oxygen and transfer the sequestered electrons to ubiquinone in vitro, providing a mechanism for superoxide scavenging distinct from that of superoxide dismutase.

Efficient production of a simple carbapenem antibiotic in Escherichia coli is achieved by a combination of feedback-resistant enzymes for increased precursor biosynthesis and inhibition of fatty acid synthesis for tolerance toward the toxic product.

A Rab11 FRET biosensor reveals a spatiotemporal interplay between Rab11 and PtdIns(3)P turnover during the removal of recycling cargo from the endosome.

Use of NMR to monitor MHC-I dynamics upon binding to the MHC-I chaperone TAPBPR explains the selection of optimal peptide sequences and release of the chaperone from the ternary peptide-MHC-I–TAPBPR complex.

Synthetic microbial consortia were engineered as experimental models of bacterial interactions within ecosystems, and mathematical models of their behavior were used to design more complex microbial systems with additional interactions.