April 17, Tue 2012
1:00 pm, MRB 100 Conference Room
Dr. Marc Ostermeier
Department of Chemical and Biomolecular Engineering, Johns Hopkins University
Protein switches and bacterial band-pass filters
The complexity of biological systems arises from the web of relationships between biological macromolecules, metabolites and signaling molecules. We seek design principles for establishing new relationships. We have created proteins that behave as switches in which enzyme catalysis is turned on by biological molecules of our choosing. Our switch design algorithm views all natural proteins as an extensive parts list of potential input and output modules from which to build switches. We employ directed evolution algorithms to recombine these modules in ways such that communication is established between previously unrelated functions. We have used this approach to create protein switches that selectively render cancer cells susceptible to drug treatment. In addition, we have established design principles for building genetic circuits that are externally tunable from outside the cell. We engineered E. coli cells to behave as an externally-tunable band-pass filter for enzyme activity and small molecules. The genetic circuit enabled bacteria growth to be patterned in response to chemical gradients in non-intuitive ways.