C. elegans as a model organism for human disease through the application of phenologs

National Center For Advancing Translational Sciences

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Abstract

This project has advanced from our Ipglycermides: Novel potent and selective inhibitors of parasitic phosphoglycerate mutase project where C. elegans serve as a model organism for infectious nematode species to test the activity of membrane permeable cyclic peptides on the viability of the organism. The ADST laboratory has developed a 384-well microtiter plate, laser cytometry-based qHTS assay to evaluate anti-nematodal agents. Primary screening is based on an overall decrease in worm number and area as measured by green fluorescence in a strain of worm ubiquitously expressing GFP. The lab is equipment with the necessary instrumentation for follow-up assays involving high-content imaging and life stage sorting to distinguish various modes-of-action for the potential chemical modulators. In collaboration with Dr. D. Sibley (NINDS, NIH) the ADST laboratory has developed a 384-well qHTS laser cytometry-based screening assay for Parkinsons Disease evaluating neurodegeneration of dopaminergic neurons in C. elegans strains containing two different human PD-linked genes. Both strains express GFP in their dopaminergic neurons allowing for traceable fluorescence intensity as a measure of neuron health over time. The ADST lab also has a long-standing collaboration with Dr. A. Golden (NIDDK, NIH) in working to develop novel genetically engineered heterozygous knockout strains of C. elegans for the Ipglycermide project. The Golden lab has provided expertise in the development of novel genetic strains of worms that may be expanded to additional disease targets.