Cardiovascular diseases are a group of diseases of the heart and blood and the leading cause of death globally. They include heart failure, arrhythmia, heart valve problems and congenital heart disease. The underlying mechanisms vary depending on the disease in question. The causes, prevention, and treatment of all forms of cardiovascular disease is an active area of biomedical research, with a considerable focus on genetic epidemiology and gene-environment interactions. Cardiac and vascular complications are complex multifactorial pathologies, in which both genetic and environmental factors are implicated, thus making them very difficult to prevent. Animal models of cardiovascular disease are essential tools to evaluate new therapeutic strategies to predict and to prevent these complications.
C. elegans is a valuable model for cardiac diseases. The pharynx of the C. elegans worm is a rhythmic muscular pump involved in feeding that bears many similarities with the heart of vertebrates both developmentally and functionally. In particular, both organs rely on similar ion channels, such as KCNQ, and do not require nervous system input for pumping.
The ScreenChip phenotyping platform enables the identification of candidate genes for heart disease, and the systematic assessment of the effects of new therapeutic agents in high-volume, whole-animal screens in an unbiased manner using C. elegans.
Introducing the ScreenChip System: a platform to study Cardiac diseases
Perform EKG-like experiments on live worms. The cardiac and pharyngeal pumping behaviors share similarities which can be exploited and explored using the ScreenChip phenotyping platform.
Visualize pumping patterns and measure pump parameters in real time.
Key advantages of the ScreenChip System:
- Visualize and understand how the pumping behavior is affected by drugs and mutations (Fig. 1)
- Get a quantitative readout of neuromuscular activity (Fig. 2)
- Reduce experimental time and variability with the rapid automated data acquisition
Visualize and understand how the pumping behavior is affected by drugs and mutations
Fig. 1: C. elegans has two homologous genes for KCNQ: kqt-1 and kqt-3. Lack of functional kqt-1 but not kqt-3 leads to arrhythmia. Pharynx activity traces (upper panels) and instant frequency over time (lower panels) are shown for one worm per strain. In control (grey) and kqt-3(aw1) (orange) worms, pumps occur at regular intervals, whereas in kqt-1(aw3) worms (green), pumps occur at irregular intervals. The longer intervals are mirrored by sudden drops in instant frequency.
Get a quantitative readout of neuromuscular activity
Fig. 2: The analysis EKG-like measurements of feeding activity in live worms reveal that the pumping defects observed in kqt-1 and kqt-3 mutants are consistent with the well-known role of KCNQ potassium channel mutations in generating cardiac arrhythmias in humans. (Left) Overlap of 50 pump events for one worm per strain. The dotted lines highlight the R (relaxation) peaks. (Right) Distribution of pump duration for one worm per strain as displayed on NemAnalysis show the probability of occurrence of pump durations between 30 ms and 170 ms. The pump duration median (red arrows) for kqt-1 (aw3) and kqt3 (aw1) higher compared to control.