Volume 21 Issue 11, November 2024

When spouses are both scientists, they mix the typical research career decisions with some marriage-related ones.

The Australian bearded dragon is so called for its distinctive ‘beard’ of spiky scales that can darken and expand during social and defensive displays. This lizard has become a reptilian model system to study the evolution, function and dynamics of neurons and neural circuits (including during sleep) in the amniote brain.

A computational mesoscale microscope offers large-scale volumetric imaging of intravital dynamics with cellular resolution.

A new generation of increasingly powerful magnets is dramatically extending the resolution, speed and analytical capabilities of magnetic resonance imaging for brain research.

Pangenome graphs signify a new frontier in genome representation. Recent advances in constructing and personalizing them mark progress in this area.

Very high-resolution images of the human brain obtained in vivo in a few minutes with MRI at an ultra-high magnetic field of 11.7 T reveal exquisite details. Biological and behavioral tests confirm the safety of the method, opening the door for human brain exploration at mesoscale resolution.

Quantitative and sensitive methods for the detection of pseudouridine (Ψ) have been lacking. Now, a method termed 2-bromoacrylamide-assisted cyclization sequencing (BACS) has been developed that enables the accurate quantification of Ψ stoichiometry, precise identification of Ψ positions and robust detection of densely modified Ψ sites.

Similarly to CRISPR–Cas systems, TnpB proteins from bacterial transposons can be employed as RNA-guided endonucleases for genome editing. By combining rational protein design and machine learning, ISDra2 TnpB variants with enhanced editing efficiency and a broader targeting range were developed, along with a prediction tool to design effective guiding RNAs.

We developed LABEL-seq, a platform that enables measurement of protein properties and functions at scale by leveraging the intracellular self-assembly of an RNA-binding domain (RBD) and protein-encoding RNA barcode. Enrichment of RBD–protein fusions, followed by high-throughput sequencing of the co-enriched barcodes, enables the profiling of protein abundance, activity, interactions and druggability at scale.

The accuracy of SCUBA-D, a protein backbone structure diffusion model trained independently and orthogonally to existing protein structure prediction networks, is confirmed by the X-ray structures of 16 designed proteins and a protein complex, and by experimental validation of designed heme-binding proteins and Ras-binding proteins.

Voltage imaging, a promising technique for directly recording neuronal activity, faces barriers to broad application due to current limitations in compatible imaging modalities. Our team introduces an advanced confocal light field microscopy method enabling high-throughput, rapid and low-noise 3D voltage imaging in awake mice.

A robotic neural recording system can sense the intended motion of the mouse that it is connected to, and it moves with the animal as it explores physical spaces. The robot can support recording interfaces that are much heavier and larger than mice and provide new capabilities for brain-wide recordings in locomoting mice.

This Review describes how photoswitchable probes and associated hardware innovations are poised to transform optoacoustic imaging in life sciences research.

PGGB is a modular framework for efficiently building unbiased pangenome graphs, supporting diverse downstream analyses.

In a technological tour de force, a whole-body 11.7-T MRI scanner has been developed. Here images of the human brain are presented while safety for the imaged human volunteers has been ascertained.

This work introduces a k-mer-based approach to customizing a pangenome reference, making it more relevant to a new sample of interest. This method enhances the accuracy of genotyping small variants and large structural variants.

This study introduces a chemical method, BACS, that generates Ψ-to-C mutation signatures, allowing for sequencing and quantification of Ψ at single-base resolution.

This work presents Strainy, a long-read metagenome assembler that allows the identification of strain distributions and mutational patterns in environmental metagenomes.

This work presents scNanoSeq-CUT&Tag, using long-read sequencing to profile histone modifications and DNA-binding proteins at the single-cell level.

Oligonucleotide-mediated proximity-interactome MAPping (O-MAP) enables precise multiomic characterization of biomolecular interaction networks at target RNAs. Distinct O-MAP workflows reveal RNA-adjacent proteins, transcripts and genomic loci.

Spatial Transcriptomics Analysis with topic Modeling to uncover spatial Patterns (STAMP) is a versatile and scalable method for dimension reduction in spatially resolved transcriptomics that enables discovery of biologically relevant tissue domains.

This work introduces engineered TnpBmax proteins with enhanced efficiency and an expanded targeting range. By leveraging an extensive dataset on editing efficiencies, it also integrates a deep learning model to predict guide RNA activity.

Labeling with barcodes and enrichment for biochemical analysis by sequencing (LABEL-seq) enables massively parallel profiling of thousands of pooled protein variants in cells, yielding insight into protein function, interactions and druggability.

SCUBA-D is a denoising diffusion probabilistic model that can perform a variety of protein backbone design tasks, including generation of backbones from random noise, from user-sketched designs, and backbones to scaffold predefined motifs that can bind small molecules or other proteins.

GlycoShape is an open-access web-based platform designed to supplement three-dimensional glycoprotein structures with missing structural information on glycans. To link them, the Re-Glyco algorithm evaluates the steric complementarity of glycans using their conformational ensemble with the protein surface.

20ExM achieves isotropic ~20× expansion of cells and tissues in a single shot for super-resolution imaging with <20-nm resolution on a conventional microscope.

A protocol for differentiating visceral sensory ganglion organoids from induced pluripotent stem cells allows the establishment of an in vitro model for the gut–visceral nerve–brain axis and study of the propagation of pathogenic proteins involved in Alzheimer’s disease along the vagus nerve.

Cortical development is influenced by morphogen gradients. To mimic patterning events during brain development, polarized cortical assembloids are generated with the help of a localized FGF8 source.

Confocal light-field microscopy allows volumetric voltage imaging in the mouse brain at speeds sufficiently high to extract the spiking activity of hundreds of neurons.

To avoid head fixation or drawbacks of miniaturized devices for freely moving rodents, a robotic device can move a headstage for microscopy or electrophysiology with the animal, thereby enabling naturalistic behavior.

This Analysis study compares computational methods for single-cell multi-omics prediction and integration, generating useful insights for method users and developers working with different analysis purposes and biological problems.