Volume 12 Issue 2, February 2016

Recently developed advanced microfluidics-based systems have outperformed known screening tools with respect to throughput, flexibility, sensitivity and tricks for hit recovery. This has enabled the discovery of novel and improved proteins from random mutagenesis libraries or metagenome-based sources.

Since the 1980s, scientists have worked on designing genetic codes to reinforce containment and control of genetically engineered microbes. New mechanistic studies of “deadman” and “passcode” gene circuits provide a flexible platform to build new safety switches.

A small molecule's biological activity in a cell depends on the actions of many gene products. Correlations between basal gene expression and compound sensitivity across hundreds of human cell lines reveal a broad view of cellular mechanisms of action.

Protein aggregation is associated with more than 50 human pathologies, including prevalent conditions such as Alzheimer's and Parkinson's diseases. A phenotypic screen in Escherichia coli associating antibiotic resistance with the inhibition of protein aggregation now allows screening for chemical inhibitors of protein aggregation in a simple, fast and inexpensive manner.

This Perspective discusses recent advances in understanding the biochemistry, enzymology and cell biology of Wnt fatty acylation and its effects on signaling and cancer.

Post-translational modifications (PTMs) of lysine side chains are important mediators of protein-protein interactions, particularly in chromatin. Photo-lysine, a diazirine analog of lysine, provides a tool to covalently capture proteins that bind lysine and its PTMs.

Cremeomycin is a diazo-containing natural product. Assignment of the functions of individual enzymes in the gene cluster for cremeomycin biosynthesis reveals a pathway by which Streptomyces cremeus converts L-aspartic acid into the nitrous acid needed for diazotization chemistry.

A new technology platform called μSCALE combines the use of a microcapillary array with laser-based extraction to enable high-throughput biochemical and biophysical analysis and isolation of protein variants for protein-engineering applications.

Synthetic biology has expanded the availability of engineered bacterial systems for diverse applications and is now developing safeguards for their effective and secure use. The report of two synthetic gene circuit ‘kill switches’ provides new biocontainment mechanisms for engineered Escherichia coli.

The binding of small-molecule inhibitors of the RSV F glycoprotein in a central cavity in the prefusion conformation stabilizes this conformation and blocks the conformational changes required for fusion with host membranes.

Applying an in vivo bacterial-based system for monitoring the influence of small molecules on the aggregation of model amyloid proteins expressed in the periplasm identified dopamine as a new inhibitor of hIAPP aggregation, a protein involved in type 2 diabetes mellitus.

Phenotypic screening in cancer cell lines combined with chemogenomics analysis reveals a correlation between DNMDP sensitivity and increased PDE3A expression. DNMDP binding to PDE3A induces a switch resulting in interactions with SLFN12 and SIRT7.

A computational tool provides a systematic approach to determine the mechanisms of action of small molecules by examining correlations between basal gene expression and small-molecule sensitivity in cancer cell lines.

Cyclophilin A binds a proline motif in human CrkII, preventing phosphorylation by Abl and EGFR. Decreased CrkII phosphorylation ensures interactions with the focal adhesion proteins paxillin and p130CAS to stimulate cellular migration.