Biology subjects

Snow, S.

Publications and source records attributed to Snow, S..

5 recordsLinked to original sources

bioRxiv2026

A rapid, sensitive, and quantitative high plex biomarker digital detection platform enabled by Hypercoding

Low-cost, multiplexed, and automated assays are needed to make omic technologies more broadly accessible in clinical, research, and commercial settings. We present Hypercoding, a scalable technology for detection and quantitation of multi-omic targets. Drawing from data reliability methods in the telecommunications field, Hypercoding uses fluorescent signals from hybridization with an error-correcting code to enable detection of high-plexity targets from biological samples, such as human DNA. In the presence of the target, a linear DNA construct is circularized, immobilized, and amplified to enable single-molecule detection of a target via rapid readout cycles within a 96-well plate. We demonstrate capability for >10,000 code plexity and accurate (98.7%) genotyping of 209 pharmacogenomic variants. Furthermore, we show computation of copy number variation with whole chromosome and sub-gene resolution, as well as quantitation of target abundance down to 10 fM sensitivity with a dynamic range of up to 10 logs.

genomics↗

bioRxiv2024

Neuronal CBP-1 is required for enhanced body muscle proteostasis in response to reduced translation downstream of mTOR

BackgroundThe ability to maintain muscle function decreases with age and loss of proteostatic function. Diet, drugs, and genetic interventions that restrict nutrients or nutrient signaling help preserve long-term muscle function and slow age-related decline. Previously, it was shown that attenuating protein synthesis downstream of the mechanistic target of rapamycin (mTOR) gradually increases expression of heat shock response (HSR) genes in a manner that correlates with increased resilience to protein unfolding stress. Here, we investigate the role of specific tissues in mediating the cytoprotective effects of low translation. MethodsThis study uses genetic tools (transgenic C. elegans, RNA interference and gene expression analysis) as well as physiological assays (survival and paralysis assays) in order to better understand how specific tissues contribute to adaptive changes involving cellular cross-talk that enhance proteostasis under low translation conditions. ResultsWe use the C. elegans system to show that lowering translation in neurons or the germline increases heat shock gene expression and survival under conditions of heat stress. In addition, we find that low translation in these tissues protects motility in a body muscle-specific model of proteotoxicity that results in paralysis. Low translation in neurons or germline also results in increased expression of certain muscle regulatory and structural genes, reversing reduced expression normally observed with aging in C. elegans. Enhanced resilience to protein unfolding stress requires neuronal expression of cbp-1. ConclusionLow translation in either neurons or the germline orchestrate protective adaptation in other tissues, including body muscle.

genetics↗

bioRxiv2020

The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

Our knowledge about the repertoire of ribosomal RNA modifications and the enzymes responsible for installing them is constantly expanding. Previously, we reported that NSUN-5 is responsible for depositing m5C at position C2381 on the 26S rRNA in Caenorhabditis elegans. Here, we show that NSUN-1 is writing the second known 26S rRNA m5C at position C2982. Depletion of nsun-1 or nsun-5 improved locomotion at midlife and resistance against heat stress, however, only soma-specific knockdown of nsun-1 extended lifespan. Moreover, soma-specific knockdown of nsun-1 reduced body size and impaired fecundity, suggesting non-cell-autonomous effects. While ribosome biogenesis and global protein synthesis were unaffected by nsun-1 depletion, translation of specific mRNAs was remodelled leading to reduced production of collagens, loss of structural integrity of the cuticle and impaired barrier function. We conclude that loss of a single enzyme required for rRNA methylation has profound and highly specific effects on organismal physiology.

cell biology↗

bioRxiv2019

Dietary restriction induces post-transcriptional regulation of longevity genes.

Dietary restriction increases lifespan through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of C. elegans subjected to dietary restriction. Transcription of muscle regulatory and structural genes increased, while increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of post-transcriptional regulation identified putative roles for RNA binding proteins, RNA editing, microRNA, alternative splicing, and nonsense mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate lifespan. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally downregulated genes. Furthermore, 3 UTR editing and intron retention increase under dietary restriction and correlate with diminished translation, while trans-spliced genes are refractory to reduced translation efficiency compared to messages with the native 5 UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense mediated decay targets, are required for increased lifespan under dietary restriction.

genomics↗

bioRxiv2018

Using EEG to characterise drowsiness during short duration exposure to elevated indoor Carbon Dioxide concentrations

Drowsiness which can affect work performance, is often elicited through self- reporting. This paper demonstrates the potential to use EEG to objectively quantify changes to drowsiness due to poor indoor air quality. Continuous EEG data was recorded from 23 treatment group participants subject to artificially raised indoor CO2 concentrations (average 2,700 {+/-} 300 ppm) for approximately 10 minutes and 13 control group participants subject to the same protocol without additional CO2 (average 830 {+/-} 70 ppm). EEG data were analysed for markers of drowsiness according neurophysiological methods at three stages of the experiment, Baseline, High CO2 and Post-Ventilation. Treatment group participants EEG data yielded a closer approximation to drowsiness than that of control group participants during the High CO2 condition, despite no significant group differences in self-reported sleepiness. Future work is required to determine the persistence of these changes to EEG over longer exposures and to better isolate the specific effect of CO2 on drowsiness compared to other environmental or physiological factors.\n\nPractical implicationsO_LIThis study introduces EEG as a potential objective indicator of the effect of indoor environmental conditions upon drowsiness\nC_LIO_LIParticipants exposed to 2,700 ppm for 10 minutes showed greater evidence of a progression towards drowsiness (as measured by EEG) than that of participants who received the same protocol without additional CO2 (mean 830 {+/-} 70 ppm), despite similar ratings of subjective sleepiness.\nC_LIO_LISubjective and objectively measured indications of drowsiness were reduced following ventilation of the room. Future work could explore the potential of regular ventilation episodes in knowledge work spaces to retain alertness.\nC_LI

physiology↗