Biology subjects

Sohrabi, S.

Publications and source records attributed to Sohrabi, S..

8 recordsLinked to original sources

bioRxiv2026

A Real-Time Automated Deep Learning Workflow for Non-invasive High-Magnification Imaging of C. elegans

Caenorhabditis elegans is a premier model organism for aging and neurobiology research, valued for its short lifespan, optical transparency, genetic tractability, and well-mapped nervous system. Non-invasive automated recording of biomarkers is a fundamental goal in modern biology because it preserves natural physiology and eliminates confounds from anesthesia, restraint, or repeated handling in C. elegans. Yet high-magnification imaging of freely moving worms remains a persistent challenge: as magnification increases, the narrowing field of view compounds target loss, motion blur, and focal drift, pushing researchers toward immobilization strategies that compromise physiology, suppress natural behavior, and preclude the continuous longitudinal observation essential for aging and neurobiological studies. Here, we present a real-time tracking workflow for imaging individual worms in a microfluidic platform under controlled culture conditions. The system integrates deep learning head detection, image-based autofocus, and rapid motorized-stage feedback to support stable imaging across multiple magnifications, including neuronal-scale imaging. Hundreds of individually housed worms in separate incubation chambers enable repeated daily imaging of the same animals throughout their lifespan. Built entirely on a commercially available inverted microscope without additional custom hardware, the platform features a modular, user-configurable interface adaptable to diverse microscope setups, specimens, and experimental goals. Fluorescence images from freely moving worms were visually comparable to those from immobilized animals, supporting longitudinal phenotyping in aging and neurobiology studies.

bioengineering↗

bioRxiv2023

Enhanced Branched-Chain Amino Acid Metabolism Improves Age-related Reproductive Function

Reproductive aging is one of the earliest human aging phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline. However, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to C. elegans oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive daf-2 mutants. Here we show that the mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes. Reduction of the BCAA catabolism enzyme BCAT-1 shortens reproduction, elevates mitochondrial reactive oxygen species levels, and shifts mitochondrial localization. Moreover, bcat-1 knockdown decreases oocyte quality in daf-2 worms and reduces reproductive capability, indicating the role of this pathway in the maintenance of oocyte quality with age. Importantly, oocyte quality deterioration can be delayed, and reproduction can be extended in wild-type animals both by bcat-1 overexpression and by supplementing with Vitamin B1, a cofactor needed for BCAA metabolism.

cell biology↗

bioRxiv2023

CeLab, a Microfluidic Platform for the Study of Life History Traits, reveals Metformin and SGK-1 regulation of Longevity and Reproductive Span

The potential to carry out high-throughput assays in a whole organism in a small space is one of the benefits of C. elegans, but worm assays often require a large sample size with frequent physical manipulations, rendering them highly labor-intensive. Microfluidic assays have been designed with specific questions in mind, such as analysis of behavior, embryonic development, lifespan, and motility. While these devices have many advantages, current technologies to automate worm experiments have several limitations that prevent widespread adoption, and most do not allow analyses of reproduction-linked traits. We developed a miniature C. elegans lab-on-a-chip device, CeLab, a reusable, multi-layer device with 200 separate incubation arenas that allows progeny removal, to automate a variety of worm assays on both individual and population levels. CeLab enables high-throughput simultaneous analysis of lifespan, reproductive span, and progeny production, refuting assumptions about the Disposable Soma hypothesis. Because CeLab chambers require small volumes, the chip is ideal for drug screens; we found that drugs previously shown to increase lifespan also increase reproductive span, and we discovered that low-dose metformin increases both. CeLab reduces the limitations of escaping and matricide that typically limit plate assays, revealing that feeding with heat-killed bacteria greatly extends lifespan and reproductive span of mated animals. CeLab allows tracking of life history traits of individuals, which revealed that the nutrient-sensing mTOR pathway mutant, sgk-1, reproduces nearly until its death. These findings would not have been possible to make in standard plate assays, in low-throughput assays, or in normal population assays.

bioengineering↗

bioRxiv2021

Novel elasticity measurement techniques reveal that the C. elegans cuticle is required for physical integrity with age

Changes in biomechanical properties have profound impacts on human health. C. elegans might serve as a model for studying the molecular genetics of mammalian tissue decline. Previously, we found that collagens are required for insulin signaling mutants long lifespan and that overexpression of specific collagens extends wild-type lifespan. However, whether these effects on lifespan are due to mechanical changes during aging has not yet been established. Here, we have developed two novel methods to study the cuticle: we measure mechanical properties of live animals using osmotic shock (OS), and we directly perform the tensile test (TT) on isolated cuticles using microfluidic technology. Using these tools, we find that cuticle, not the muscle, is responsible for changes in stretchiness of C. elegans, and that cuticle stiffness is highly non-linear and anisotropic. We also found that collagen mutations alter integrity of the cuticle by significantly altering elasticity. Additionally, aging stiffens the cuticle under mechanical loads beyond the cuticles healthy stretched state. Measurements of elasticity showed that long-lived daf-2 mutants were considerably better at preventing progressive mechanical changes with age. These tests of C. elegans biophysical properties suggest that the cuticle is responsible for their resilience.

biophysics↗

bioRxiv2021

CeAid: A smartphone application for logging and plotting C. elegans assays

C. elegans is used as a model organism to study a wide range of topics in molecular and cellular biology. Conventional C. elegans assays often require a large sample size with frequent manipulations, rendering them labor-intensive. Automated high-throughput workflows may not be always the best solution to reduce benchwork labor, as they may introduce more complexity. Thus, most assays are carried out manually, where logging and digitizing experimental data can be as time-consuming as picking and scoring worms. Here we report the development of CeAid, C. elegans Application for inputting data, which significantly expedites the data entry process, utilizing swiping gestures and a voice recognition algorithm for logging data using a standard smartphone or Android device. This modular platform can also be adapted for a wide range of assays where recording data is laborious, even beyond worm research.

genetics↗

bioRxiv2020

Metabolic defects cause hyperactive mitochondria and Parkinson disease-like traits

Metabolic dysfunction is a facet of many age-related neurodegenerative diseases, yet its role in disease etiology remains poorly understood1. We recently discovered a potential causal link between the branched-chain amino acid transferase, BCAT-1, and the neurodegenerative movement disorder, Parkinsons disease (PD)2. Knockdown of C. elegans bcat-1 recapitulates PD-like features, including progressive motor deficits and neurodegeneration with age2. Using transcriptomic, metabolomic, and imaging approaches, we show that bcat-1 knockdown increases mitochondrial activity and induces oxidative damage in neurons through mTOR-independent mechanisms. We recently developed a high-throughput screening platform to identify drugs that may be repurposed for PD, and found that metformin, the leading type 2 diabetes medication, significantly improves motor function in bcat-1(RNAi) worms3. Late-in-life metformin treatment restores normal mitochondrial activity levels and protects against bcat-1-associated neurodegeneration. Our results suggest that PD may originate as a metabolic disorder, and highlight metformin as a promising new drug candidate for PD treatment.

neuroscience↗

bioRxiv2020

High-throughput behavioral screen in C. elegans reveals novel Parkinson disease drug candidates

We recently linked branched-chain amino acid transferase 1 (BCAT1) with the movement disorder Parkinsons disease (PD), and found that reduction of C. elegans bcat-1 causes abnormal spasm-like curling behavior with age. Here, we report the development of a high-throughput automated curling assay and its application to the discovery of new potential PD therapeutics. Four FDA-approved drugs were identified as candidates for late-in-life intervention, with metformin showing the greatest promise for repurposing to PD.

neuroscience↗

bioRxiv2018

Reducing tau ameliorates behavioural and transcriptional deficits in a novel model of Alzheimer’s disease

SummaryOne of the key knowledge gaps blocking development of effective therapeutics for Alzheimers disease (AD) is the lack of understanding of how amyloid beta (A{beta}) and tau cooperate in causing disease phenotypes. Within a mouse tau deficient background, we probed the molecular, cellular and behavioural disruption triggered by wild-type human taus influence on human A{beta}-induced pathology. We find that A{beta} and tau work cooperatively to cause a hyperactivity phenotype and to cause downregulation of gene transcription including many involved in synaptic function. In both our mouse model and in human post-mortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau depletion in the mice, initiated after behavioural deficits emerge, was found to correct behavioural deficits, reduce synaptic tau levels, and substantially reverse transcriptional perturbations, suggesting that lowering tau levels, particularly at the synapse, may be beneficial in AD.\n\nHighlights- Expression of human familial Alzheimers associated mutant amyloid precursor protein and presenillin 1 with wild-type human tau in the absence of endogenous tau in a novel MAPT-AD mouse model results in behavioural deficits and downregulation of genes involved in synaptic function.\n- Tau is present in pre and postsynaptic terminals in MAPT-AD mice and human AD brain. In mice, lowering synaptic tau levels was associated with improved cognition and recovered gene expression.\n- These data suggest that A{beta} and tau act cooperatively in impairing synaptic function and that lowering tau at synapses could be a beneficial therapeutic approach in AD.

neuroscience↗