Revealing protein switch design principles through directed evolution

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CBET-0828724OstermeierEngineered protein switches hold great promise as biosensors, selective protein therapeutics and tools for programming cells for biotechnological applications. A lack of understanding switch structure and function limits the ability to create them. Directed evolution approaches to switch construction have been developed by the Principal Investigator (PI). However, for many applications this approach is limited by the ability to screen/select for switches with desired properties. An understanding of switch design principles would greatly facilitate switch construction and enable these applications. The combinatorial nature of directed evolution, when carefully applied, is ideally suited for elucidating these design principles. A series of directed evolution experiments will be performed that are designed to answer specific questions about switch mechanisms and answer practical question on switch construction. The lab of the PI is a multidisciplinary environment. The PI mentors students from several departments and programs at Johns Hopkins University including chemical and biomolecular engineering, biomedical engineering, biology, the chemistry-biology interface program and the computational and molecular biophysics program. Of the seven graduate students the PI currently supervises, five are female and one is of Hispanic descent.