ZEBRAFISH AS A MODEL SYSTEM FOR BIOMEDICAL RESEARCH

DESCRIPTION: The goal of this project is to develop a transposable element-based gene transfer system and related technologies such as gene tagging for the zebrafish. We currently have limited abilities to create transgenic zebrafish and current methods do not offer researchers in this field the opportunity to create such organisms with the ease required for the full integration of this technology into their research programs. Consequently, a vital and powerful tool remains underdeveloped and underutilized, retarding the development of zebrafish into the powerful model system for biomedical research it could become. The project outlined here takes an unprecedented approach to creating a transgenic vertebrate by employing a short inverted repeat type transposable element of the mariner/Tc1 superfamily of elements. Four specific aims are described including determining the precision of integration of Ts1 into zebrafish genomes, determining the frequency of insertional inactivation of zebrafish genes by Ts1 vectors, determining the effects of the Ts1 vector system on endogenous zebrafish transposons and determining the mechanisms of Ts1 regulation. The project relies on a host of biochemical and genetic approaches to address these specific aims.