RUI: Developing modular repressors as in vivo biosensors in various organisms

University Of Texas At Tyler, Tyler TX

Investigators

Abstract

The overall goal of this research is to establish an approach to construct new biological components that would advance the understanding of novel cellular behavior for practical applications. At this point in time, scientists are capable of designing complex genetic networks to generate desirable biological behavior. However, the implementation of many network designs is hampered by the lack of modular components to build flexible and rewireable connections between different parts of genetic networks. In this project, the research team is establishing a design principle for generating modular chemical sensors within various organisms. These sensors build new linkages between environmental signals and gene expression regulation. The design principle is used to develop biosafety devices in various organisms, enhancing the safety levels of using these organisms in industrial and clinical settings. Products of this project will facilitate the creation of genetically modified organisms in many biotechnology industries. This project also provides opportunities for undergraduate student training in synthetic biology at the University of Texas at Tyler. An undergraduate team is established to join an international synthetic biology competition (iGEM), in which participants will develop engineered biological entities to solve problems involving genetic engineering. Outreach activities to promote synthetic biology among K-12 students are also planned. The research team is implementing a range of scientific approaches, including protein structure analysis, bioinformatics, computational modeling, and in vivo transcription assay, in identifying DNA-binding modules and allosteric response modules in different repressor families, such as LacI and TetR. These modules are mixed and matched to generate resulting hybrid repressors that possess novel combinations of signal detection and DNA operator recognition properties. These recognition properties are harnessed to build new cellular response pathways in genetic circuits for creating novel cellular behavior. Specifically, the research team is using these hybrid repressors to establish a biocontainment platform that can be implemented in various organisms. The engineered organisms are constrained to survive only in a highly specific condition. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.