Project 443854

The dynamic behavior of cells during development, tumorigenesis and other disorders remain largely unclear. The genomic DNA of a cell stores the blueprint of life in sequences that can be represented by four basic residues, Adenine (A), Cytosine (C), Guanine (G), and Thymine (T). It has been proposed that DNA can be utilized as an extremely small, robust, and heritable form of information storage media. This project will develop "DNA event recording" systems by which high-resolution information of cells is progressively stored in cell-embedded "DNA tapes." Coupled with high-throughput single-cell sequencing technologies, such a system would enable access to molecular and cellular history information of cells at the time of observation and provide a way of observing the dynamics of complex biological systems in high-resolution. Like a tape recorder, DNA event recording requires (1) "memory" such as high-capacity DNA "tapes" embedded in chromosomes, (2) "signal to information conversion" such as molecular sensors to capture cell lineage and differentiation, (3) information "writers" such as genome editing technologies, and (4) an information "reader" such as high-performance computing systems. We will extend the development of genetic circuits, mouse and cell engineering, and high-performance computing technologies that we have successfully piloted for these four system requirements and obtain a whole-body cell lineage and cell type differentiation map of mammalian (mouse) development at the resolution of single cells. The whole-body mammalian developmental map will be an essential resource for life and health sciences and for the education of generations to come.