NIRT: Direct Electronic Sensing of Biomolecular Activity and Signaling

该奖项支持响应纳米科学与工程倡议NSF 03-043 NIRT类别而提出的项目。 通过该奖项支持的研究人员将开发一种创新的电子架构，以构建新型分子传感器。 该架构将采用碳纳米管耦合到单个生物活性分子，如肌球蛋白轻链激酶（MLCK）。 利用激酶识别和结合事件产生的电子签名，跨学科团队打算在单分子极限下探索酶活性和生物分子动力学。 在这个极限下，可以明确地识别由特定生物分子相互作用产生的电子信号，并且可以直接测量蛋白质-蛋白质相互作用和构象变化的相关时间尺度。 通过纳米管传感器平台实现的实时、高带宽信号采集使得能够从特定的生物相互作用中搜索可再现的电子签名。 为了监测这样的信号，碳纳米管电路将被定制为使用噬菌体展示技术将单个MLCK和钙调蛋白分子结合在一起，以分离和合成用于有效附着和转导的特殊分子试剂。 为了减轻单一方法无法达到研究目标的风险，将开发两种互补的传感架构。 其中一种方法是，蛋白质活性将调节基于纳米管的晶体管的导电性;另一种方法是，蛋白质涂层的纳米管尖端将形成电化学电极。 除了他们的研究议程，研究人员的目标是启动和发展一个跨学科的研究小组，为本科生，研究生和研究生研究人员的教育。 这个合作小组将开发一个实践培训环境，来自不同领域的学生研究人员可以共同研究需要专业化的研究项目，包括纳米材料合成，分析化学以及化学和分子生物学。该组织还将扩大一个针对高中生的研究实习计划，包括那些传统上代表性不足的群体。 该实习计划将建立在调查人员在较小规模上进行的成功努力的基础上。

This award supports a project proposed in response to the Nanoscale Science and Engineering initiative, NSF 03-043, category NIRT. The investigators supported through the award will develop an innovative electronic architecture to construct novel molecular sensors. The architecture will employ carbon nanotube coupled to individual, biologically active molecules such as the myosin light chain kinase (MLCK). Using the electronic signatures generated by kinase recognition and binding events, the interdisciplinary team intends to explore enzymatic activity and biomolecular dynamics at the single molecule limit. At this limit, the electronic signals generated by a particular biomolecular interaction can be unambiguously identified, and the relevant time scales for protein-protein interactions and conformational changes can be directly measured. The real-time, high bandwidth signal acquisition made possible by the nanotube sensor platform enables a search for reproducible electronic signatures from particular biologic interactions. In order to monitor such signals, carbon nanotube circuits will be tailored to incorporate individual MLCK and calmodulin molecules using phage display techniques to isolate and synthesize special molecular agents for effective attachment and transduction. To mitigate the risk that a single approach will fail in reaching the research goal, two complementary sensing architectures will be developed. In one, protein activity will modulate the conductivity of a nanotube-based transistor; in the other, a protein-coated nanotube tip will form an electrochemical electrode. In addition to their research agenda, the investigators aim to initiate and grow an interdisciplinary research group for the education of undergraduate, graduate and postgraduate researchers. This collaborative group will develop a hands-on training environment where student researchers from disparate fields can work together on research projects requiring specializations encompassing nanomaterials synthesis, analytical chemistry, and chemical and molecular biology. The group will also extend a research internship program for high school students, including those from traditionally underrepresented groups. This internship program will build upon successful previous efforts conducted by the investigators at a smaller scale.