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Zebra Fish Screening

Zebra Fish Screening: Michael Pack Ph.D

A great advantage of zebra fish is the ability to perform high throughput assays in a living organism. Although not as efficient as biochemical or cell-based HTS, these studies have the advantage of analyzing the function of genes and pharmacological agents in a specific biological context. These high throughput assays include both genetic and pharmacological (small molecule) screens to identify genes that regulate cell behavior, organ development, or pathogenesis. Furthermore, using the zebra fish, one can analyze mechanisms of gene function using embryological assays not amenable to other model systems.

As an example of capability in the area of zebra fish genetics and assay development, Dr. Pack developed a strategy to identify genes and pharmacological compounds that regulate cancer progression using the zebra fish. In this mutagenesis screen, Dr. Pack identified a recessive lethal mutation, meltdown (mlt), which causes cystic expansion of the larval zebra fish intestine. Cyst formation in mlt mutants occurs as a result of stromal invasion of posterior intestinal epithelial cells. Epithelial invasion in mlt mutants is regulated by the ectopic expression of genes causally linked to human cancer progression. Inhibition of these cancer progression genes rescues mlt mutants.

 


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