Zebra Fish Screening: Michael Pack Ph.D
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.
|
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.