C. elegans as a model for screening and studying human monogenic disease mutations

The decreasing cost of whole genome sequencing and the push toward personalized medicine is driving an exponential growth in the number of human patients who have their genomes sequenced. An outstanding challenge is to identify which of the myriad genetic changes identified contribute directly to pathological conditions and how. C. elegans has proven to be an excellent model for investigating the molecular and cellular basis of many human diseases, including proteinopathies, neurodegenerative, metabolic, muscular atrophy, and kidney-related diseases.

We are working to make CRISPR-Cas9 genome editing more efficient, to increase the throughput of screening human variations suspected of causing disease. In parallel, we are also using bioinformatics to identify human genetic variations that are worth testing in the worm. We are collaborating with human geneticists from Hadasa hospital in Ein Karem on this project. Working with religious Jewish and Arab populations that have a high degree of inbreeding they have many patients with genetic diseases to be identified.

Thus, CRISPR-Cas9 genome editing in C. elegans will enable us to separate the wheat from the chaff in the pile of human genetic variation data and generate disease models that will be useful for in-depth functional analysis of disease etiology and for high-throughput drug screening.