CAREER: Protein Switches for Molecular Biotechnology

David W.WoodBES-0348220这项研究的目标是开发一类具有广泛潜在应用的新的配体触发的自剪接和自切割蛋白家族。在实践中，开关蛋白将在DNA水平上与各种靶蛋白融合，产生功能不活跃的前体。工程开关蛋白与小分子配体的结合将触发开关根据特定应用的需要进行剪接或切割，通常导致融合目标蛋白的激活。这些蛋白质开关的开发将深入了解人工多功能蛋白质的设计和行为，特别是在变构结构域融合领域，并将包括理性和基于进化的方法的方面。初步结果表明，这些蛋白质开关立即用于生物传感和药物研发，生物分离方面的新技术即将问世。长期应用包括药物输送、代谢工程，甚至生物分子计算。拟议的教学材料旨在为学生提供信息和技能，使他们能够在工程学和生物学的交界处做出更大贡献，包括高中实习生计划，在工程学入门课程中使用学习风格评估，以及应用生物技术系列研讨会。

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.