K. A. Johnson

DNA targeting by compact Cas9d and its resurrected ancestor

This study reports cryo-EM structures of Cas9d, revealing its DNA targeting mechanism and demonstrating a compact variant with robust nuclease activity in mammalian cells.

Unraveling the mechanisms of PAMless DNA interrogation by SpRY Cas9

This study investigates how SpRY-Cas9 recognizes DNA targets without requiring a PAM sequence, revealing structural and kinetic mechanisms that improve genome editing versatility.

Super-resolution imaging of neuronal structure with structured illumination microscopy

The paper uses structured illumination microscopy to achieve super-resolution imaging of a thick mouse brain section, achieving 144 nm resolution, 1.7x better than conventional widefield imaging.

Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2

The paper identifies SM04690, a CLK2 inhibitor, as a YAP activator by promoting alternative splicing of AMOTL2, leading to reduced YAP phosphorylation and membrane localization.

A concerted mechanism involving ACAT and SREBPs by which oxysterols deplete accessible cholesterol to restrict microbial infection

This paper identifies a mechanism by which oxysterols like 25HC deplete accessible cholesterol from plasma membranes via ACAT activation and SREBP suppression to restrict microbial infection.

An mTOR-independent Macroautophagy Activator Ameliorates Tauopathy and Prionopathy Neurodegeneration Phenotypes

The paper identifies CCT020312, an mTOR-independent autophagy activator, which reduces tauopathy and prionopathy neurodegeneration phenotypes by enhancing autophagy flux and clearing protein aggregates.

Integrity of membrane fluidity and fatty acid environment are necessary for Ebola virus VP40 assembly and release of viral particles

This study shows that membrane fluidity and fatty acid composition are critical for Ebola virus VP40 assembly and viral particle release.

Brain charts for the human lifespan

The paper introduces brain charts as a standardized resource for benchmarking brain morphology across the human lifespan using MRI data from a large and diverse cohort.

Integrating Subclonal Response Heterogeneity to Define Cancer Organoid Therapeutic Sensitivity

The paper evaluates individual patient-derived cancer organoids using optical metabolic imaging to predict therapeutic response and identify subclonal populations and resistance mechanisms.

Impact of baseline culture conditions of mouse-derived cancer organoids when determining therapeutic response and tumor heterogeneity

This study evaluates how baseline culture conditions affect therapeutic response and heterogeneity in mouse-derived cancer organoids, finding that initial size is the key factor influencing growth and response.

Structural basis for mismatch surveillance by CRISPR/Cas9

This study identifies a linear gRNA:DNA duplex conformation that prevents Cas9 activation in the presence of PAM-distal mismatches, offering insights for improving Cas9 specificity.

Conformational dynamics during misincorporation and mismatch extension defined using a DNA polymerase with a fluorescent artificial amino acid

This study investigates the conformational dynamics and kinetics of nucleotide misincorporation and mismatch extension in a high-fidelity DNA polymerase using fluorescent unnatural amino acids and molecular dynamics simulations.

Remdesivir is a delayed translocation inhibitor of SARS CoV-2 replication in vitro

This study shows remdesivir inhibits SARS-CoV-2 RNA polymerase by blocking RNA translocation after three base incorporations, leading to delayed chain termination.

Flexible multiplane structured illumination microscope with a four-camera detector

The paper introduces a multi-camera structured illumination microscope that captures 3D fluorescent images without axial movement, enabling rapid 3D imaging modes.

Amplification, not spreading limits rate of tau aggregate accumulation in Alzheimer's disease

The paper quantifies tau aggregate replication rates in Alzheimer's disease and finds local replication, not spreading, limits tau accumulation in neocortical regions.

Kinetic and thermodynamic analysis defines roles for two metal ions in DNA polymerase specificity and catalysis

This study analyzes the roles of two Mg2+ ions in DNA polymerase specificity and catalysis using kinetic analysis and molecular dynamics simulations.

Assessing Attention Orienting in Mice: A Novel Touchscreen Adaptation of the Posner-Style Cueing Task

This study adapts the Posner task for mice using touchscreen technology to assess attention orienting and tests the effects of methylphenidate and atomoxetine on performance.

Sphingomyelin suppresses Hedgehog signaling by restricting cholesterol accessibility at the ciliary membrane

This study identifies sphingomyelin's role in restricting cholesterol accessibility at the ciliary membrane, thereby suppressing Hedgehog signaling.

Basis for discrimination by engineered CRISPR/Cas9 enzymes

This study investigates how engineered CRISPR/Cas9 variants improve off-target discrimination by analyzing their kinetic behavior during DNA cleavage.

DNA unwinding is the primary determinant of CRISPR-Cas9 activity

The paper investigates CRISPR-Cas9 activity, finding that DNA unwinding is the primary determinant of its cleavage efficiency.