The Digital Fish Project‐ In toto imaging and FlipTraps for Digitizing Development

The genome provides a program for creating an organism. Understanding how this program works will require moving from the one‐dimensional string of letters that has now been determined for the genomic code to understanding how this code is executed in the 4‐dimensions of space and time of a developing embryo. We are developing imaging‐based techniques that allow genome function to be probed quantitatively and systematically across the dimensions of space and time. Specifically, in toto imaging uses time‐lapse, laser‐scanning microscopy to track all the cells in a developing tissue and custom developed software to extract quantitative, cell‐based data. We are using in toto imaging to determine complete lineages of developing tissues and to quantitate gene/protein expression patterns. FlipTraps, a novel gene‐trapping approach, allow a variety of data to be read‐out in vivo including protein expression patterns, transcriptional expression patterns, protein subcellular localizations, and conditional mutant phenotypes. As part of our Center of Excellence in Genomic Science, we are scaling‐up and integrating these approaches to generate quantitative, systematic data suitable for a systems biology based approach to development.