CAREER: Photoregulated Gene Expression for Spatiotemporal Control of Morphogenesis

CBET 1151035/Gersbach生物技术、生物化学和生物质工程项目的NSF CAREER奖支持开发一种新技术，用于用光控制哺乳动物细胞中的基因表达。 用于控制哺乳动物细胞中基因表达的系统在医学、生物制药生产、生物技术和基础科学中具有多种应用。 然而，目前的基因调控系统不能有效地控制细胞或组织群体内基因表达的空间组织。 基因表达的位置控制对许多过程至关重要，例如由多种细胞类型组成的复杂组织的工程化。 此外，目前的系统仅控制人工添加到细胞中的基因，而不是控制天然染色体背景中的基因。 为了解决这些局限性，将对植物中的光敏蛋白进行重新设计，使它们能够控制哺乳动物细胞中的特定靶基因。 将在人类细胞中评估这些工程蛋白控制基因表达和催化基因组序列响应光的特异性变化的能力。 曝光模式将用于设计结构复杂的组织，其中组织发育的空间组织可以任意编程。 这项工作将为工程师和科学家开发新的工具，以设计和研究细胞系统，提高组织工程和组织发育和细胞-细胞相互作用研究中的应用精度。 这个研究项目的主题也将转化为教育计划，培养工程和科学教育的热情和创造力，并在小学，初中和高中，本科和研究生水平垂直整合。 该计划将与美国国家工程院大挑战K12合作伙伴计划合作实施。 该计划还将通过高中和本科生在PI实验室的研究教育经验，本科和研究生课程开发以及在各级研究和教育中纳入代表性不足的群体来补充。

CBET 1151035/ GersbachThis 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.