CAREER: Protein Switches for Molecular Biotechnology

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David W. WoodBES-0348220The objective of this proposed study is to develop a new family of ligand-triggered self-splicing and self-cleaving proteins with a wide variety of potential applications. In practice, the switch proteins will be fused to various target proteins at the DNA level to generate functionally inactive precursors. The binding of a small molecule ligand by the engineered switch protein will trigger the switch to splice or cleave as desired for a particular application, typically resulting in the activation of the fused target protein. The development of these protein switches will yield insights into the design and behavior of artificial multifunctional proteins, particularly in the area of allosteric domain fusions, and will include aspects of rational as well as evolution-based approaches. Preliminary results imply immediate uses for these protein switches in biosensing and drug discovery, and new technologies in bioseparations are forthcoming. Long term applications include drug delivery, metabolic engineering and even biomolecular computation. The proposed pedagogical materials seek to provide students with information and skills to allow them to make greater contributions at the interface between engineering and biology, and include a high school intern program, the use of learning style evaluations in an introductory engineering course and a seminar series in applied biotechnology.