Biology subjects

Kain, P.

Publications and source records attributed to Kain, P..

4 recordsLinked to original sources

bioRxiv2026

Enabling subcellular DESI-MSI for broad adoption: Acquisition, analysis, and application

Subcellular mass spectrometry imaging (MSI) has required specialized instrumentation and approaches. Additionally, data analysis has required expensive proprietary software, or code-based open-source tools. These barriers render spatial metabolomics less accessible than peer spatial omics techniques (transcriptomics, proteomics). Here we demonstrate subcellular MSI on standard commercial hardware, analyzed using code-free, open-source software. An inexpensive, fully reversible modification of a stock DESI source takes the platform past its typical 5-10 m pixels to routine 2x2 m pixels, and 1x1 m in proof-of-principle experiments. At a tissue-glass boundary imaged at 2x2 m, tissue-specific ions showed no measurable spillover onto the adjacent glass within the {+/-}4.4 m uncertainty of the edge position. To make these data interpretable, we extend MSI.EAGLE, an open-source, vendor-agnostic application with two new methods: i) Spatial UMAP preserves tissue architecture alongside subcellular detail, where conventional clustering breaks apart at high resolution; ii) Histology Fit performs landmark-free co-registration, and recovers synthetic misalignments of up to 8 m to within one pixel of a reference registration. Together, these enable previously high-burden spatial metabolomics experiments. In mouse brain tissue, we demonstrate genuine subcellular signal by resolving mitochondrial cardiolipin into perinuclear puncta, quantifying cytoplasmic enrichment across 6,073 cells. Cell identities are assigned to MSI pixels using histology-predicted transcriptomics, linking cell provenance to metabolism in 2D space directly. Finally, we recover cell-type-specific metabolomes consistent with the transcriptomic identities. This workflow allows cellular and subcellular spatial metabolomics linked to cell provenance, with only stock MSI hardware, open-source GUI-based software, and common histology techniques, putting it within reach of many researchers and laboratories.

molecular biology↗

bioRxiv2026

Peripheral Metabolic Reprogramming Links TDP-43 Proteinopathy to Sleep Disruption

Sleep disruption is an early and prevalent feature of neurodegenerative disease, commonly attributed to neuronal circuit dysfunction or cell loss. However, sleep is tightly coupled to metabolic state, raising the possibility that systemic metabolic abnormalities contribute to disease-associated sleep phenotypes. Using Drosophila models of TDP-43 proteinopathy, we investigated whether peripheral metabolic dysfunction plays a causal role in sleep disruption. We show that TDP-43 expression induces a chronic, starvation-like metabolic state characterized by depletion of peripheral carbohydrate stores despite normal feeding. Restoration of sleep fails to correct these metabolic defects, whereas improving peripheral metabolic state robustly rescues sleep. A modifier screen of [~]650 RNAi lines identified Salt-inducible kinase 3 (SIK3) as a potent suppressor of both sleep loss and starvation sensitivity. Transcriptomic and spatial metabolomic analyses reveal that SIK3 selectively remodels a peripheral metabolic program centered on the pentose phosphate pathway and redox-associated metabolites without globally restoring energy stores. Together, these findings identify systemic metabolic dysfunction as a key driver of sleep disruption in TDP-43 proteinopathy and highlight peripheral metabolism as a potential therapeutic entry point for sleep dysfunction in neurodegenerative disease.

neuroscience↗

bioRxiv2025

MSI.EAGLE: An Open-Source GUI for Streamlined Mass Spectrometry Imaging Analysis

Mass Spectrometry Imaging (MSI) is an emergent tool for analyzing spatial molecular distributions, yet data complexity often hinders effective analysis. MSI.EAGLE, an open-source R-Shiny application, makes analysis accessible for non-specialists by integrating advanced tools in a user-friendly interface. The workflow leverages tools from the Cardinal MSI package, with enhanced phenotyping, segmentation, statistical analysis and visualization. The application addresses a gap in spatial biology research by empowering a broader scientific community.

pathology↗

bioRxiv2022

Activity and state dependent modulation of salt taste behavior in Drosophila melanogaster

Sodium present in NaCl is a fundamental nutrient required for many physiological processes. In animals, including Drosophila, low-salt concentrations induce attraction and high-salt concentrations evoke aversive behavior. Although the cellular basis of low and high salt taste detection has been described, the mechanisms regulating high salt consumption and salt taste modulation in animals remain elusive. Thus, we investigated the neural mechanisms behind high NaCl consumption in adult Drosophila, focusing on how flies adjust their acceptance of high salt based on their diet. Our findings show that long-term exposure to high salt increases the taste sensitivity of pharyngeal LSO neurons, which, in turn, enhances high salt intake. Exposing flies to a high NaCl diet for three days shows a decline in high salt aversion under starvation. Our results suggest that this modulation requires active LSO neurons and a starvation state or dopamine as genetic suppression of LSO pharyngeal neuronal activity in high NaCl-fed flies inhibit excessive salt intake. We also found that several independent taste receptor neurons and pathways are involved in such a modulation. Silencing any one of multiple LSO neuronal types inhibits excessive salt intake. Our study suggests that flies can adapt to the amount of salt ingested over several days, indicating the presence of a critical mechanism that resets the salt appetite and related neural circuits.

neuroscience↗