Using C. elegans notch mutants in an undergraduate cancer biology laboratory course to demonstrate oncogenic effects on cell proliferation

Abstract

Undergraduate laboratory exercises addressing aspects of cancer biology such as increased cell proliferation, gain-of-function signaling mutations and tumour formation often rely on tissue culture or even small mammal models. Many departments have limited or no access to these tools, and even well-equipped departments face logistical problems when incorporating these models into laboratory classes. I have developed a laboratory exercise using the microscopic worm, C. elegans, to demonstrate the effects of Notch receptor mutations on cell proliferation. Notch, which is activated by juxtacrine signaling, is mutated in many human cancers. In this exercise, students compare the germline phenotypes of worms that have a loss-of-function Notch mutation (no cells in the germline) or a gain-of-function Notch mutation (over-proliferation resulting in a germline tumour). Students also genotype the worms and perform sequence analysis to determine the effects of the mutations on the protein sequence. This laboratory exercise demonstrates oncogenic proliferation, correlates genotype to phenotype, exposes students to model organisms and introduces sequence databases and analysis. In addition to cancer biology courses, this exercise could be incorporated in courses with a focus on genetics, cell biology or developmental biology.

Keywords:

• Mutation
• cancer
• C. elegans
• laboratory exercise
• development

Acknowledgments

I am grateful to student Kaylyn Fuller for assistance in piloting the lab and to the many students who took Biology of Cancer, particularly those whose images are included. Strains were provided by the Kimble lab and the CGC, which is supported by the National Institutes of Health – Office of Research Infrastructure Programs (P40 OD010440). I thank Kurt Lucin for critical reading of the manuscript.