A High-Throughput Approach for Designing Novel Cell-Based Signal Integrators | AIChE

A High-Throughput Approach for Designing Novel Cell-Based Signal Integrators

Authors 

Keenan, J. L. - Presenter, Boston University
Siggers, T. W., Boston University
Understanding the mechanisms by which cells sense, integrate, and respond to complex environmental signals is essential not only for understanding healthy and disease states, but also for engineering cells that are able to detect and respond to pathological conditions. Traditionally, cellular signal integration has been studied through the characterization of natural integration systems. As a complementary approach, we are developing a high-throughput biophysically-motivated technique to design novel signal integrators. To do this, we use protein-binding microarrays (PBMs) to screen tens of thousands of candidate DNA response elements (DREs) for sequences that are cooperatively bound by two signal-dependent transcription factors (TFs) in the presence of an engineered scaffold protein, called miniCBP. We anticipate this approach will both enable a deeper understanding of the design principles underlying cellular signal integration and provide a generalizable platform for regulating transgene expression in response to environmental stimuli.