High-throughput screening in the C. elegans nervous system

Kinser, Holly E; Pincus, Zachary

doi:10.1016/j.mcn.2016.06.001

Cited by 19 publications

(14 citation statements)

References 82 publications

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“…They are also unsuitable for the culture of plants. Furthermore, in order for high resolution in vivo observations to be carried out, these systems require FLN movement to be constrained within an artificial medium 12 , 119 – 122 . We have proposed an approach that combines newly developed transparent soils with improved chemistry for biocompatibility of the matching liquid and modular growth chambers for control of soil environmental conditions.…”

Section: Discussionmentioning

confidence: 99%

New live screening of plant-nematode interactions in the rhizosphere

O’Callaghan

Braga

Neilson

et al. 2018

Sci Rep

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Free living nematodes (FLN) are microscopic worms found in all soils. While many FLN species are beneficial to crops, some species cause significant damage by feeding on roots and vectoring viruses. With the planned legislative removal of traditionally used chemical treatments, identification of new ways to manage FLN populations has become a high priority. For this, more powerful screening systems are required to rapidly assess threats to crops and identify treatments efficiently. Here, we have developed new live assays for testing nematode responses to treatment by combining transparent soil microcosms, a new light sheet imaging technique termed Biospeckle Selective Plane Illumination Microscopy (BSPIM) for fast nematode detection, and Confocal Laser Scanning Microscopy for high resolution imaging. We show that BSPIM increased signal to noise ratios by up to 60 fold and allowed the automatic detection of FLN in transparent soil samples of 1.5 mL. Growing plant root systems were rapidly scanned for nematode abundance and activity, and FLN feeding behaviour and responses to chemical compounds observed in soil-like conditions. This approach could be used for direct monitoring of FLN activity either to develop new compounds that target economically damaging herbivorous nematodes or ensuring that beneficial species are not negatively impacted.

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Section: Discussionmentioning

confidence: 99%

New live screening of plant-nematode interactions in the rhizosphere

O’Callaghan

Braga

Neilson

et al. 2018

Sci Rep

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“…The nematode Caenorhabditis elegans (C. elegans) is a free-living organism that has a simple and well-defined nervous system with a fully sequenced genome which makes it appealing for neuroscience research [2,3] . Although a hermaphrodite worm only possesses 302 neurons, it can perceive and respond to a wide range of stimuli such as chemicals, light, temperature, electric field (EF), and touch through the developed sensory amphid, phasmid, labial, and mechanosensory neurons [4][5][6][7][8][9] . C. elegans behaviors, including movement, egg-laying, and food intake are regulated by these sensory modalities and behavioral screening provides a great means to study neuronal functions and processes in C. elegans.…”

Section: Introductionmentioning

confidence: 99%

Electric Egg-Laying: Effect of Electric Field in a Microchannel onC. elegansEgg-Laying Behavior

Youssef

Archonta

Kubiseski

et al. 2020

Preprint

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In this paper, the novel effect of electric field (EF) on adult C. elegans egg-laying in a microchannel is discovered and correlated with neural and muscular activities. The quantitative effects of worm aging and EF strength, direction, and exposure duration on egg-laying is studied phenotypically using egg-count, body length, head movement, and transient neuronal activity readouts. Electric egg-laying rate increases significantly when worms face the anode and the response is EF-dependent, i.e. stronger (6V/cm) and longer EF (40s) exposure result in a shorter egg laying response duration. Worm aging significantly deteriorates the electric egg-laying behaviour with 88% decrease in the egg-count from Day-1 to Day-4 post young-adult stage. Fluorescent imaging of intracellular calcium dynamics in the main parts of the egg-laying neural circuit demonstrate the involvement and sensitivity of the serotonergic hermaphrodite specific neurons (HSNs), vulva muscles, and ventral cord neurons to the EF. HSN mutation also results in a reduced rate of electric egg-laying allowing the use of this technique for cellular screening and mapping of the neural basis of electrosensation in C. elegans. This novel assay can be parallelized and performed in a high-throughput manner for drug and gene screening applications.

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“…High-throughput screening (HTS) is a crucial drug discovery process that aims to test large compound libraries on a specific target in a sensitive, fast, and cost-effective manner [ 1 ]. Typically, preliminary hits are achieved by using in-vitro cell-based assays.…”

Section: Introductionmentioning

confidence: 99%

“…Very commonly, these compounds are found to be impractical on whole animals due to the drug toxicity, metabolism complications, or poor target engagement, thereby rendering the process expensive and tedious [ 2 ]. Model organisms such as Caenorhabditis elegans ( C. elegans ) [ 1 , 3 , 4 ], Drosophila melanogaster [ 5 , 6 ], and Danio rerio [ 7 ] have shown promising outcomes to fill the gap between in-vitro cell-based and in-vivo whole-animal studies.…”

Section: Introductionmentioning

confidence: 99%

Parallel-Channel Electrotaxis and Neuron Screening of Caenorhabditis elegans

et al. 2020

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In this paper, we report a novel microfluidic method to conduct a Caenorhabditis elegans electrotaxis movement assay and neuronal imaging on up to 16 worms in parallel. C. elegans is a model organism for neurodegenerative disease and movement disorders such as Parkinson’s disease (PD), and for screening chemicals that alleviate protein aggregation, neuronal death, and movement impairment in PD. Electrotaxis of C. elegans in microfluidic channels has led to the development of neurobehavioral screening platforms, but enhancing the throughput of the electrotactic behavioral assay has remained a challenge. Our device consisted of a hierarchy of tree-like channels for worm loading into 16 parallel electrotaxis screening channels with equivalent electric fields. Tapered channels at the ends of electrotaxis channels were used for worm immobilization and fluorescent imaging of neurons. Parallel electrotaxis of worms was first validated against established single-worm electrotaxis phenotypes. Then, mutant screening was demonstrated using the NL5901 strain, carrying human α-synuclein in the muscle cells, by showing the associated electrotaxis defects in the average speed, body bend frequency (BBF), and electrotaxis time index (ETI). Moreover, chemical screening of a PD worm model was shown by exposing the BZ555 strain, expressing green fluorescence protein (GFP) in the dopaminergic neurons (DNs), to 6-hydroxydopamine neurotoxin. The neurotoxin-treated worms exhibited a reduction in electrotaxis swimming speed, BBF, ETI, and DNs fluorescence intensity. We envision our technique to be used widely in C. elegans-based movement disorder assays to accelerate behavioral and cellular phenotypic investigations.

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High-throughput screening in the C. elegans nervous system

Cited by 19 publications

References 82 publications

New live screening of plant-nematode interactions in the rhizosphere

New live screening of plant-nematode interactions in the rhizosphere

Electric Egg-Laying: Effect of Electric Field in a Microchannel onC. elegansEgg-Laying Behavior

Parallel-Channel Electrotaxis and Neuron Screening of Caenorhabditis elegans

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