CAREER: Photoregulated Gene Expression for Spatiotemporal Control of Morphogenesis

Duke University, Durham NC

Investigators

Abstract

CBET 1151035/ Gersbach This NSF CAREER award by the Biotechnology, Biochemical and Biomass Engineering program supports the development of a new technology for controlling the expression of genes in mammalian cells with light. Systems for controlling the expression of genes in mammalian cells have diverse applications in medicine, biopharmaceutical production, biotechnology, and basic science. However, current systems for gene regulation are not able to effectively control the spatial organization of gene expression within a population of cells or tissue. The positional control of gene expression is critical to many processes such as the engineering of complex tissues made of multiple cell types. Additionally, current systems only control genes that have been artificially added to cells, rather than controlling genes in their natural chromosomal context. To address these limitations, light-sensitive proteins from plants will be reengineered so that they control specific target genes in mammalian cells. The ability of these engineered proteins to control gene expression and catalyze specific changes to the genome sequence in response to light will be assessed in human cells. Patterns of light exposure will be used to engineer architecturally complex tissues in which the spatial organization of tissue development can be arbitrarily programmed. This work will develop new tools for engineers and scientists to design and study cellular systems with enhanced precision for applications in tissue engineering and studies of tissue development and cell-cell interactions. The theme of this research project will also be transformed into educational programs that foster enthusiasm and creativity in engineering and science education and are vertically integrated across elementary, middle and high school, undergraduate, and graduate levels. The program will be implemented in collaboration with the National Academy of Engineering Grand Challenges K12 Partners Program. This program will also be complemented by research education experiences in the PI's laboratory by high school and undergraduate students, curriculum development at the undergraduate and graduate level, and the inclusion of underrepresented groups across all levels of research and education.