CAREER: Deciphering Design Principles of Early Embryonic Cell Cycles

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Biological clocks are genetically controlled processes that allow organisms to anticipate environmental changes, which are central to developmental biology. This project will develop a synthetic biology framework to reveal quantitative information on clock cycles and how this cycle influences cellular architecture. The project will use this framework to address how the mitotic clock is designed to achieve robust cell cycles in young embryonic zebrafish cells. Given that biological clocks exist ubiquitously in organisms from bacteria to humans this project will provide insights into developmental biology and diseases, including cancer. This highly interdisciplinary research will serve as a training resource for K-12, undergraduate and graduate students to gain experience in theoretical modeling, optical imaging, nanofabrication, developmental biology, data analysis and scientific communication. Outreach activities will include demonstrations at museums and lab open days developed in collaboration with local professional educators. The goal of this project is to establish a synthetic biology approach to decipher the fundamental design principles of a mitotic circuit that drives early cell cycles in zebrafish embryos. This project will develop a cell-free system, build artificial cells to reconstitute mitotic events that resemble the processes of early embryonic cell divisions, and develop novel single-cell imaging and tracking systems. The results in the cell-free system will be tested in live embryos to assess their biological relevance. The objectives of this project are to: 1) establish computational methods and search for all robust and tunable oscillation topologies, 2) artificially construct mitotic cells and examine its topology for functions of robustness and tunability, and 3) combine in vitro and in vivo studies to evaluate the role of mitotic clocks in live zebrafish embryos. The findings may be generalizable to a wide spectrum of biological clocks that share similar core architecture with the mitotic clock.