CAREER: Nucleic acid circuitry for programming gene expression

这项工作将使利用核酸控制细胞行为的潜在变革性技术成为可能。PI将设计合成分子电路，可以分析活细胞内的RNA表达，并在此基础上自主控制基因表达。PI将表明核酸回路可以区分不同的细胞类型和状态，并且只能在细胞的一个子集中特异性地调节靶基因。该项目的中心目标是通过将药物传递与传感和逻辑相结合，提高传统反义和基于sirna的治疗方法的特异性。具体的研究目标是：(i)设计基于杂交的分子传感器，用于检测活细胞中的RNA；（ii）基于反义寡核苷酸和沉默RNA的可控分子致动器设计；（iii）构建用于条件基因调控的集成传感器-执行器系统。该程序为构建基因表达可编程控制的复杂多组分电路提供了基础。这项工作将为基因表达的时空控制提供新的分子工具，在疾病治疗和基础生物学研究中具有广泛应用的潜力。拟议的研究与一个有两个主要目标的外展计划紧密结合在一起。第一个目标是建立一个教育框架，教授在合成生物学研究中取得成功所需的跨学科技能。第二个目标是利用这个框架来吸引和吸引那些传统上不参与生命科学研究的学生，或者不考虑注册电子工程或计算机科学项目的传统轨道之一（PI的家庭部门是EE和CS）。

0954566SeeligThe proposed work will enable a potentially transformative technology for controlling cellular behavior using nucleic acids. The PI will engineer synthetic molecular circuitry that can analyze RNA expression inside living cells and { based on this analysis { autonomously control gene expression. The PI will show that nucleic acid circuitry can distinguish between di_erent cell types and states and can specifically regulate a target gene only in a subset of cells. A central aim of this project is to increase the specificity of conventional antisense and siRNA-based therapeutics by combining drug delivery with sensing and logic. Specific research objectives are: (i) The design of hybridization-based molecular sensors for the detection of RNA in living cells; (ii) the design of controllable molecular actuators based on antisense oligonucleotides and silencing RNA; (iii) the construction of integrated sensor-actuator systems for conditional gene regulation. This program provides the basis for the construction of complex multi-component circuits for programmable control of gene expression. This work will lead to new molecular tools for temporal and spatial control of gene expression, with the potential for wide-spread applications in disease therapy and in basic biology research. The proposed research is tightly integrated with an outreach program with two main aims. The first aim is to develop an educational framework that teaches the interdisciplinary skills required to succeed in synthetic biology research. The second aim is to leverage this framework to attract and engage students who are not traditionally involved with life-science research, or would not consider enrolling in one of the traditional tracks in an electrical engineering or computer science program (the PI's home departments are EE and CS).