Synchronize and Associate Visual Phenotypes with Feeding Behavior
To understand the mechanisms of action of your proteins or drugs, it is important to understand the behaviors (social behaviors, reward behaviors, sickness behaviors, and avoidance behaviors) of overall worm populations as well as phenotypes (specific phenotypes such as unc, dpy, dumpy, RNAi, and blister) that reveal the underlying cellular and molecular forces in action. The ScreenChip™ System, along with the WMicrotracker System, allow you to get in-depth understanding of worm behavior.
The ScreenChip™ System, a C. elegans visual screening and phenotyping platform allows you to associate visual phenotypes with feeding behavior.
Measure, visualize and analyze the neuromuscular aspects of feeding behavior
Assess the neuronal and physiological responses to drugs, aging, genetic modifications or environmental changes (Fig. 1 & 2)
Perform multiple phenotyping analyses at once, i.e., morphology, fluorescence, defecation, and feeding behavior while your worm is immobilized in the chip
Aging nematodes exhibit irregularity in inter-pump intervals (below).
No significant change is observed in pump duration upon nematode aging (data not shown).
Pump amplitude increases with age
Nematodes exhibit a higher pump amplitude with age (below); this is concomitant with the larger, stronger pharynx of developed adult worms.
Average pump frequency is observed to decrease with nematode age (below).
Anti-aging and lifespan effects are quantifiable
Changes in nematode pump frequency recapitulate the effects of age-associated decline
Trehalose treatment mitigates the effects of ageing, in support of prior work reporting that trehalose extends nematode lifespan
Humanized worm recapitulates function and physiology
A Customized C. elegans Model for Epilepsy
Comparison of the human STXBP1 sequence to the worm’s unc-18 gene exhibits only 59% identical amino acid usage
Disease variant biology more accurately modeled by focusing on gene-swap humanization rather than the native animal locus
Sequence optimized human cDNA inserted at start codon of worm unc-18; all endogenous coding removed, transgene uses native 3' UTR
Humanized C. elegans Shows Functional Rescue
Pharynx pumping trace exhibits full loss of WT pumping activity in STXBP1 ortholog unc-18 KO (below)
Gene-swap of hSTXBP1 at the worm unc-18 locus shows functional rescue in pharyngeal pumping phenotype
Conservation of Physiology in the Humanized Worm
79% of disease genes are conserved between human and worm
STBXP1 is ranked as the #6 likely genetic cause of epilepsy; of the 349 variants, 47 are pathogenic (13%)
Rescued function and physiology paves the way for screening pathogenic gene variants
Visualize whole-worm pharmocological effects via EPG
Reported Compound Effects Recapitulated in EPG Analysis
Inhibitory neuromuscular effects of Ivermectin (IVM) are observed as an abrupt loss of pharyngeal pumping activity (right)
No effect on neuromuscular activity is observed in worms experiencing a mock-drug treatment
IVM resistant nematodes exhibit the expected pharmacological effect of persistent partial activity
Compound Treatment Results in Quantifiable EPG Changes
EPG traces exhibit shifts in observed amplitude, frequency, and duration upon exposure to IVM (right; pre-treatment in black, 35min treatment in blue)
EPG traces can be analyzed for multiple parameters in parallel; effects of candidate compounds can be distinctly characterized
The ScreenChipTM System can also be used in the field of toxicology to quantify adverse effects of chemical substances (e.g., environmental pollutants, drugs) on living organisms. Learn more about toxicology testing.
With the ScreenChip System, you can:
Record videos that are perfectly synchronized to the EPG traces, all with a single software.
Observe and playback all the molecular and cellular events in the pharynx to better understand what is happening to your worms.
All you need is a microscope (inverted or dissection), a vacuum source and a computer that meets the minimum requirements for running the ScreenChip Software.
Please ensure that your microscope includes the following basic requirements:
a C-mount or CS-mount camera port
For magnifications 10X or 20X: inverted
For 40X magnification: standard long working distance objective (higher magnification not suitable with the ScreenChip system)
Cold light source (LED)
Fluorescence: The ScreenChips are 100% optically clear and compatible with all light wavelengths (excitation and acquisition).
What we use in our lab:
Leica M165 FC - Fluorescent dissecting microscope
Zeiss Axiovert - High magnification (40X and up) inverted microscope
We haven't tested other brands and models, however microscopes with similar specifications should work well with the ScreenChip system.