Expanding the Genetic Code of Zebrafish

Abstract

In nature, the basic building blocks for proteins are comprised of twenty common amino acids. All life on earth exists on the complexity of how these natural amino acids are assembled in proteins. The template for proteins is encoded in the genetic material (DNA and RNA) and every cell has the machinery to process this information to synthesize proteins. The possibility to expand the complexity of proteins though chemical synthesis of new (unnatural) amino acids with new properties shows significant promise in understanding and improving protein function. The challenge is to alter the machinery that translates the DNA into proteins such that unnatural amino acids can be incorporated into this process. This project will alter the genetic code of the zebrafish, an animal model favored by many researchers, to expand the number of amino acids it can use to build proteins. This will become the first vertebrate animal with an expanded genetic code of 21 amino acids and will be a major advance as it provides novel tools to explore and unravel the mysteries of how cells, tissues, and organs form in first few days of life. By initially focusing on light-activated amino acids, this research will enable precise optical control over protein function with unprecedented spatial and temporal resolution in zebrafish. Controlling protein function using a light switch will provide answers to fundamental biological questions about zebrafish developmental biology that has relevance to human embryogenesis.

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