[Research and development of combinatorial bioengineering using zebrafish and its application on drug discovery]

The main challenge of the post-genomic era is to functionally characterize genes identified by the genome sequencing projects. Model organisms, including zebrafish (Danio rerio), are indispensable for this demanding task. Zebrafish has recently been successfully incorporated into large-scale genetic screens due to the optical clarity of the embryos and their accessibility to various experimental techniques throughout development. The attractiveness of the zebrafish as a model organism is enhanced by the biological availability of continuously improving genomic tools and methodologies for functional characterization of the genes. In addition, transparent zebrafish embryos are well suited to manipulations involving DNA or mRNA injection, cell labeling, and transplantation. Once the scheduled zebrafish genome project is complete, targeted genetic manipulations in zebrafish would be able to become even more desirable. In my laboratory, we propose that the "embryoarray technology" supports to characterize especially unknown proteins using zebrafish embryos which offer a platform for assessing the biological effects by not only chemical compounds including medical drugs, siRNAs (small interfering RNAs) and micro RNAs, but foreign genes that are never existing in zebrafish. Thus, zebrafish offers a high-quality, high-throughput bioassay tool for determining the biological effect of small molecules as well as for dissecting biological pathways. In this review, I would like to introduce a couple of recent data that we have constructed the gene expression system in zebrafish and have succeeded to produce several membrane-associated proteins. Furthermore, several tools with zebrafish embryos are available to examine the interactions between protein-protein using fully automatic high-throughput microinjection system.