Standardized Parts for the Orthogonal Control of Signaling Enzymes

The development of standardized parts for controlling signaling pathways could allow new functions to be engineered into living systems as well as enable fundamental studies of cellular signaling pathways. To realize these goals, new approaches to controlling protein function are needed. Our laboratory is utilizing split-protein reassembly to develop a lexicon of split-protein modules for biologically important signaling proteins. These modules will be coupled with the new host-guest pairs described above to allow for the orthogonal control of multiple signaling enzymes in living cells.

New Host-Guest Systems for Use in Living Cells

Supramolecular assembly represents a potentially powerful approach to control the oligomerization of a host protein by addition of a small-molecule guest. However, more work is needed to identify host-guest pairs that are capable of functioning in living cells. Our laboratory has described an approach that enables to the design of miniprotein hosts capable of supramolecular assembly in response to addition of a cognate small-molecule. These new host-guest pairs can be utilized in living cells and provide a basis for controlling cellular signaling networks as well as designing new materials.