Current projects in the lab are focused on the organizing principles and mechanisms of biological networks. In cell signaling, scaffold proteins physically organize cell signaling networks and can facilitate signaling by directing signals to the correct target. Outstanding challenges for the field are to understand, at a molecular level, how scaffold proteins accelerate signaling reactions and how scaffold proteins themselves are regulated to direct signals. Addressing these questions allows us to engineer designer scaffolds to control biological pathways.

Molecular Mechanisms of Crosstalk and Coordination

Scaffold proteins physically assemble components of cell signaling pathways, and are themselves regulated to control the flow of signaling information. We are attempting to biochemically reconstitute the interactions between scaffold proteins and their targets in pathways that control cell fate decisions in humans and other animals. Our goal is to understand, at the molecular level, how crosstalk between signaling pathways is regulated to integrate and prioritize multiple signals.

Programmable RNA Scaffolds for Metabolic Engineering

We have developed new synthetic biology tools using the CRISPR-Cas platform and programmable RNA molecules to control gene expression. This system allows the construction of genetic programs in which a single, synthetic master regulator controls a multi-gene response with simultaneous activation and repression of target genes. We are using this system to control metabolic networks for microbial biosynthesis.

Spatially-Organized Cell Signaling

How do scaffold proteins organize signaling proteins for efficient reactions? Can scaffold proteins act to significantly reduce entropic barriers for protein-protein interactions? To develop a predictive framework for the relationship between scaffold protein structure and function, we are designing synthetic scaffolds to systematically control the distance and orientation between signaling proteins.