The Role of Zebrafish in Chemical Genetics

Joachim      Berger; Peter      Currie

Abstract

The identification and exploration of new drug candidates to fight diseases is a major imperative for improving human health. The traditional mechanism utilised to identify new compounds with therapeutic potential has been to systematically analyse large libraries of small molecules for lead compounds with a desired bioactivity in protein or cell based assays. Identified lead compounds were subsequently assessed for their potential as lead drugs. In the last few years, small molecule screens were also carried out in vivo, on whole organisms such as the zebrafish. Cost efficient maintenance together with abundant manipulatory techniques and molecular tools have made the zebrafish a preferred system in which to perform large-scale screens. Numerous studies have revealed that zebrafish mutants can accurately model many aspects of human diseases. Therefore, small molecules identified in zebrafish-based screens can be particularly valuable in identifying lead compounds with direct therapeutic relevance to specific human disease states. Here, we review the role of zebrafish-based screens in the emerging field of chemical genetics.

Keywords: Chemical genetics, large-scale small molecule screen, zebrafish, drug discovery, drug target, lead compound, lead drug, targeted library