Janelia Research Campus

Dystrophic changes of nigrostriatal axons harboring a SYNJ1 Parkinson’s mutation suggest catastrophic failure of endocytic mechanisms

Synaptojanin 1 is a brain enriched phosphoinositide phosphatase implicated in endocytosis at the synapse. A mutation (R258Q) that selectively impairs its Sac1 phosphatase domain causes early onset familial Parkinsonism. Neurons of mice with this mutation display synaptic vesicle...

Self‐Supervised Internal Learning Enhances Isotropic Resolution for Three‐Dimensional Fluorescence Microscopy

ABSTRACT Three‐dimensional fluorescence microscopy often exhibits anisotropic resolution because axial information is poorly sampled and more blurred than lateral information, which complicates quantitative interpretation of fine 3D structures. Although optical remedies and compu...

Multi-organelle signatures map cell-state diversity and metabolic adaptation in tissues

Cell-state diversity drives tissue adaptability, repair, and disease resilience, but capturing this complexity is a challenge. Current approaches rely on transcriptional profiling and overlook organelle structure, a key indicator of metabolism and stress. We developed spatial Org...

Live dynamics of induced cell-cell fusion between mitotic and interphasic cells

The cell cycle is tightly regulated by checkpoint mechanisms that ensure faithful duplication and segregation of the genome. Here, we induced cell-cell fusion between mitotic and interphase cells to study how nuclei from different cell cycle stages behave in a shared cytoplasm. W...

Rapidly evolving aphid gall effector proteins exhibit saposin-like folds

Abstract Many insects manipulate plants by injecting effector proteins. In one extreme example of this molecular “hijacking”, Hormaphis cornu aphids inject bicycle proteins into Hamamelis virginiana , contributing to the development of novel organs called galls. Bicycle proteins...

Population morphology implies a common developmental blueprint for Drosophila motion detectors

Abstract T4 and T5 neurons are the first direction-selective neurons in the visual pathway. They are the most numerous cell types in the fly brain (∼ 6000 within each optic lobe) and, as a population, their compact dendritic arbours span the entire visual field. They are classifi...

De novo design of RNA pseudoknots with deep learning

RNA design has been hindered by the limited accuracy of 3D structure prediction. Here, we show that intricate RNA structures can be generated with current deep learning tools through accurate de novo design of pseudoknot secondary structures. In an Eterna competition involving 57...

Form and function of actin impacts actin health and aging

Abstract The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin...

A Workflow for the Identification of Oligomeric Structures on Tilted Sample Planes in Cryo-SMLM

We introduce a workflow to identify oligomeric structures that are recorded with single-molecule localization microscopy (SMLM) under cryogenic conditions. Typically, these oligomers are assumed to consist of protomers arranged as equilateral two-dimensional polygons and every pr...