Technology development for functional genomics and systems biology
Transposon “Calling Cards”
There is still a great deal to learn about the design principles that guide vertebrate development. Since all cells in an organism contain the same genes, transcribing different sets of genes is what confers a cell’s specialized role. Which genes get turned on or off to create a particular cell type at the right time, in the right place during the development of an organism? This is one of the pivotal questions in developmental biology. We have developed a technology, Transposon “Calling Cards,” to attack this question in a novel way, and we have shown that it works in yeast and mammalian cell culture and completed proof-of-principle experiments in living zebrafish. This technology can record gene expression along different cell lineages throughout the development of a living vertebrate. We will produce a complete record of gene activation at different stages of development, watching as cells and their progeny specialize and form organs. These data will contribute to the field by providing a blueprint for the generation of many cell types, and could ultimately guide the reprogramming of embryonic or induced pluripotent stem cells to produce specific cell types.
Methylation and Development
Epigenetic modifications of DNA play an important role in mammalian development because they act to specify and maintain the expression state of different genes in different cell lineages. Epigenetic marks such as DNA methylation regulate the transcription of nearby genes. During development, different cell types establish different patterns of DNA methylation to ensure expression of the correct sets of genes needed for their specialized functions. There is still much that is not known about how epigenetic modifications are initiated, how they act to influence gene expressions and how their patterns change in disease. A deeper knowledge of the epigenetic code is needed if we are to fully understand development, tissue homeostasis, and cancer. We are developing methods to analyze methylation patterns in complex tissues. We are also actively investigating how patterns of DNA methylation are established in different tissues.