California Institute of Technology
To create a synthetic cell fate control system
Multicellular organisms operate through cell differentiation. What begins as an initial pool of uniform, isogenic cells eventually develops into a suite of distinct cell types, each performing specialized functions in the organism as a whole. This specialization process can be thought of as a form of information processing . A simplified overall picture of this information processing is that a receptor -for instance at the cell membrane- detects a signal molecule and a signaling network then acts as 'wiring' to relay information to downstream components, which then produce an appropriate cellular response. The signaling network is a chain of biochemical events which link an upstream molecular signal to a downstream 'cis-regulation' system in order to achieve a particular gene-expression pattern that--in this case--specifies cell type. This grant supports work by Michael Elowitz, Professor of Biology and of Bioengineering at Caltech, to create a synthetic cell fate control system. The system, if successful, will allow one to begin with a pool of genetically identical cells and then -using a small number of 'input' signals- direct various subsets of the pool to differentiate and develop into distinct, predetermined cell types. Elowitz proposes to achieve this goal by using the tools of synthetic biology to develop the two core subsystems briefly sketched above: a 'signaling network'; a complex network of proteins to process chemical 'signals' and relay them downstream and a downstream 'cis-regulation' system that drives expression of a specific gene or set of genes. The signaling network and gene regulation system will be integrated into natural cells to demonstrate cell fate control and differentiation into targeted cell types. If successful, this project will advance our understanding of and control over cellular information processing and provide a foundation for extending synthetic biology into multicellularity.