20-BBSRC/NSF-BIO: Synthetic Control of Pattern Formation and Morphogenesis in a Purposefully Rewired Vertebrate Cell

The cell cortex is responsible for responding to a variety of internal and external signals with the appropriate mechanical behavior. Such behaviors include cell division, cell locomotion and short or long-term cell shape changes. We and others have recently discovered a dynamical process-cortical excitability-that a variety of cell types harness to drive distinct mechanical behaviors. Cortical excitability is outwardly manifest as propagating cortical waves of actin assembly and complementary waves of the various macromolecules that control actin assembly. Cortical excitability is itself controlled by coupled fast positive feedback and delayed negative feedback. We will develop the means to synthetically induce cortical excitability in cells that do not normally display it, namely, frog oocytes, and employ high-resolution live cell imaging to capture the detailed features of excitability. The induction will be based on synthetic protein constructs engineered to produce either fast positive feedback or delayed negative feedback. By combining different synthetic constructs, we will drive simple cell shape changes (i.e., furrowing) or complex cell shape changes (i.e., gastrulation), allowing us to test basic ideas about cell shape control. In addition, by iteratively combining experiments with computational modeling, it will be possible to develop both a quantitative, mechanistic understanding of processes such as cell division and morphogenesis.

The goal of this project is to synthetically (artificially) control the behavior of the cell "cortex"-the outermost layer of the cell. It is the cortex that normally powers many fundamental biological processes, both within single cells, and in tissues and organs. Completion of the project will result in four important research outcomes: first, it will test current ideas about how living systems execute such processes as cell division, cell movement, and cell shape change. Second, it will provide new tools and technologies that permit manipulation of cell behavior in living organisms. Third, it will provide the means to promote new, and potentially beneficial cell behaviors. Fourth, it will result in the development of new computational approaches for the analysis and understanding of complex cell behaviors.