Volume 16 Issue 8, August 2019

Analyzing super-res microscopy images ASAP, strengthened by Ultimate Frisbee.

You can look back there to explain things, but the explanation disappears. You’ll never find it there. Things are not explained by the past. They’re explained by what happens now. –Alan Watts

We propose a network of national imaging centers that provide collaborative, interdisciplinary spaces needed for the development, application, and teaching of advanced biological imaging techniques. Our proposal is based on recommendations from a National Science Foundation (NSF)-sponsored workshop on realizing the promise of innovations in imaging and computation for biological discovery.

The PLUMED consortium unifies developers and contributors to PLUMED, an open-source library for enhanced-sampling, free-energy calculations and the analysis of molecular dynamics simulations. Here, we outline our efforts to promote transparency and reproducibility by disseminating protocols for enhanced-sampling molecular simulations.

DNA microscopy is an optics-free method for encoding physical images in DNA.

A newly developed method allows structure elucidation of proteins inside intact mammalian cells, using solid-state NMR spectroscopy.

A humanized version of the RNA-targeting Cas13 can regulate RNA abundance and translation.

The concept of reference frames inspires researchers to develop a differential ranking system for measuring relative differential abundance, which does not require information about absolute microbial load.

Illuminating the brain for optogenetic experiments can have undesirable effects on neural activity.

Nanopore sequencing’s early adopters are pushing the limits of what can be achieved with ultra-long DNA reads, and they are also finding innovative ways to apply this technology to other biological questions.

This review provides an overview of machine learning techniques in protein engineering and illustrates the underlying principles with the help of case studies.

Conos constructs a joint graph between single cells in different samples based on multiple pairwise alignments of the samples and identifies recurrent subpopulations across all of the datasets.

A genetically encodable protein synthesis inhibitor (gePSI) for cell-specific inhibition of protein synthesis that is efficient and reversible enables the study of structural plasticity following single-synapse activation in neurons.

The search engine Thesaurus detects and quantifies phosphopeptide positional isomers from data-independent acquisition and parallel reaction monitoring mass spectrometry data, enabling studies of how neighboring phosphosites are regulated.

The red form of the photoconvertible fluorescent protein mEos4b has a long-lived dark state with specific chromophore conformation. Weak 488-nm light depopulates this state, improving track lengths in single-particle tracking experiments.

The automated structures analysis program (ASAP) enables rapid and objective detection, classification and analysis of cellular assemblies in super-resolution images.

scGen predicts cellular responses to phenomena absent from the training data. Such out-of-sample predictions are shown across cell types and species.

CombiSEAL is a high-throughput platform for seamlessly assembling barcoded combinatorial genetic units, offering an approach for protein optimization such as screening SpCas9 variants.

DIVERS uses replicate sampling and spike-in sequencing to distinguish temporal and spatial variations from noise in microbial samples.

A software tool, EPIC, is developed to determine protein complex membership using chromatographic fractionation–mass spectrometry data, and is applied to map the global Caenorhabditis elegans interactome.

A nuclear magnetic resonance spectroscopy-based approach to monitor multiple molecule and reaction types at once, Systems NMR, provides in vitro insights into complex biomolecular network dynamics.

A method for analyzing scRNA-seq data sets based on correlations of gene expression allows construction of an atlas of the Drosophila wing disc.

A technique to ‘lift out’ samples of interest from high-pressure-frozen specimens expands applications of cryo-electron tomography to multicellular organisms and tissue.

The genetically encoded GABA sensor iGABASnFR allows visualizing GABA signaling in vivo. Its application is demonstrated in mouse slices, in the awake mouse and in behaving zebrafish.

High-affinity sensors for free ubiquitin can be used to quantify intracellular ubiquitin pools, visualize ubiquitin levels by microscopy of fixed cells and enable real-time deubiquitination assays of diverse ubiquitin–protein conjugates.

A two-photon computed tomography approach, called scanned line angular projection microscopy, enables high-speed imaging at over 1 kHz frame rates, as demonstrated for glutamate imaging in the in vivo mouse brain.