NIH Director's Pioneer Award

纳米结构由于其在电子学、光子学和微电子学中的应用前景而受到广泛关注。 信息存储我相信这些微小的结构也具有巨大的潜力， research.特别是，我一直想利用纳米结构的力量，从根本上改变 细胞行为被探测和调节。在这里，我建议开发下一代工具集， 通过将三类互补的纳米结构结合在一起来操纵细胞活性：金纳米笼 能够吸收近红外光并有效地将其转化为热量;智能聚合物能够改变 构象响应于温度的微小变化;和酶。刺激响应聚合物将 共价连接到酶活性位点附近的特定位置;所得单元将被缀合 金纳米笼的表面。当用脉冲激光撞击纳米笼时，聚合物构象将 在伸展和折叠状态之间快速可逆地转换，打开和关闭酶。到 为了证明这种混合纳米结构的生物学重要性，我将首先应用它们来操纵细胞， 行为如凋亡。还将采用各种诱捕技术来控制昆虫的空间位置。 在单个细胞内部和外部的混合纳米结构。第一次，我将能够确定 启动细胞凋亡所需的最小数量的活性酶，以及是否和如何空间位置的细胞凋亡。 酶影响细胞凋亡信号传导。一旦它被证明用于细胞凋亡，这个概念将被扩展到 开发类似的混合纳米结构用于阅读和控制其他细胞过程和信号通路。 这种基于空间和时间可寻址纳米结构的工具集与许多其他工具集是互补的。 生物成像技术正在开发中，并将在研究复杂的生物系统中找到广泛的用途。

Nanostructures have received extensive attention for their promising applications in electronics, photonics, and information storage. I believe these minuscule structures also hold great potential for advancing biomedical research. In particular, I have always wanted to harness the power of nanostructures to radically change the way cell behavior is probed and regulated. Here I propose to develop the next generation of toolset for studying and manipulating cell activity by bringing together three classes of complementary nanostructures: gold nanocages capable of absorbing near infrared light and effectively converting it to heat; smart polymers capable of changing conformation in response to small variation in temperature; and enzymes. The stimuli-responsive polymer will be covalently attached to a specific position near the active site of the enzyme; the resultant unit will be conjugated to the surface of gold nanocage. When the nanocage is struck with a pulsed laser, the polymer conformation will be quickly and reversibly switched between the extended and collapsed states, turning on and off the enzyme. To demonstrate the biological importance of such hybrid nanostructures, I will initially apply them to manipulate cell behavior such as apoptosis. A variety of trapping techniques will also be adapted to control the spatial position of the hybrid nanostructure inside and outside an individual cell. For the first time, I will be able to ascertain the minimum number of active enzymes required to initiate apoptosis, and whether and how the spatial location of the enzyme affects apoptosis signaling. Once it has been demonstrated for apoptosis, the concept will be extended to develop similar hybrid nanostructures for reading and controlling other cellular processes and signaling pathways. Such a toolset based on spatially and temporally addressable nanostructures is complementary to many other bioimaging techniques under development, and will find broad use in studying complex biological systems.