Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders

Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo d...

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A transcriptional biosensor reveals mechanisms of α-ketoglutarate signaling to chromatin

The metabolite α-ketoglutarate (αKG) is required for chromatin demethylation, but mechanisms that control αKG abundance in the nucleus are poorly defined. We designed a biosensor to monitor this metab...

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Reversible suppression of autophagy in a mouse model reveals neuronal resilience

Impairments in intracellular quality-control mechanisms, including autophagy, affect neuronal integrity and function. Despite numerous studies aimed at slowing neuronal deterioration, it remains uncle...

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Ubiquitin-like proteins NEDD8 and SUMO2 control epithelial homeostasis, regeneration, and inflammation

Stratified epithelial differentiation involves transcriptional and proteomic remodeling. Here, multiomic profiling implicated ubiquitin and related posttranslational networks in differentiation dynami...

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Antibiotics stimulate protein transfer to persister cells

The exchange of biological matter between bacterial cells drives adaptation and evolution. However, whether bacteria can exchange functional proteins remains unclear. In this work, we found that antib...

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The oscillatory biology of sleep: Linkage to dementia

During wakefulness, neuromodulators operate largely independently to support behavior and cognition. By contrast, sleep reorganizes their activity into a coordinated brain rhythm. During sleep, the ma...

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Microtubule dynamics control the direction of cardiomyocyte growth

The adult heart grows by the addition of sarcomeres along the length or width of individual cardiomyocytes, yet how directional growth is spatially coordinated remains unclear. We found that microtubu...

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Programme Leader Track - MRC Laboratory of Medical Sciences

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Microtubule dynamics control the direction of cardiomyocyte growth

The adult heart grows by addition of sarcomeres along the length or width of individual cardiomyocytes, yet how directional growth is spatially coordinated remains unclear. Here, we found that microtu...

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Repurposing of a DNA segregation machinery into a cytoskeletal system controlling cell shape

Bacteria, like eukaryotes, use conserved cytoskeletal systems for intracellular organization. The plasmid-encoded ParMRC system forms actin-like filaments that segregate low–copy number plasmids. In m...

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Stem cell control in the lung by an autocrine injury-activated Igf complex

Stem cells proliferate after injury to repair damaged tissue, and chronic injury can promote cancer. However, the injury-activated signals and regulatory mechanisms, and their relationship to cancer, ...

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Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration

Why mammals cannot regenerate limbs like amphibians do presents a long-standing puzzle in biology. To uncover the underlying differences, we compared amputation responses of embryonic mouse (Mus musculus) and Xenopus laevis tadpole limbs. Lowering ...

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Pearling drives mitochondrial DNA nucleoid distribution

The distribution of mitochondrial DNA–containing nucleoids is essential for mitochondrial function and genome inheritance; however, no known mechanisms can explain nucleoid segregation or their regula...

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Harnessing viral strategies to reverse cognitive dysfunction through the integrated stress response

The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15BR...

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Systems-level organization of extracellular proteostasis

One defining feature of complex organisms is the ability to maintain protein homeostasis beyond cellular boundaries. We review how extracellular proteostasis is organized as a hierarchical network spa...

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Host-derived nitrate fuels indole production by Escherichia coli to drive chronic kidney disease progression

Chronic kidney disease (CKD) is linked to an elevated fecal abundance of Enterobacteriaceae, but the ecological drivers of this shift and its impact on disease progression remain unclear. The uremic t...

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