Identify spatial strategies used within cells to control the interactions of kin

细胞内信号的空间控制（Lee Bardwell，主题负责人）| 生物空间动力学中的一些最大的奥秘在于亚细胞水平。生物化学和基于重组的分析在解释细胞生物学基本机制方面取得的成功，使人们很容易忽视这样一个事实：细胞不仅仅是一袋袋燃烧良好的酶。关于细胞内信号传导途径，越来越多的证据表明空间控制对正常功能至关重要[192-194]， 发生在许多尺度上：在这些水平之下，是由局部束缚相互作用定义的纳米空间尺度。 这种空间调控必然是动态的：支架蛋白移动到质膜，激酶和转录因子移入或移出细胞核，拴系相互作用受磷酸化等调节。此外，基于马达的运输既用于构建隔室，又用于运输信号分子，进而这种运输受细胞外和细胞内线索的调节。然而，对于所有 尽管有证据表明空间很重要，但我们对细胞内的空间动力学的了解往往比细胞外的少。 我们提出了三个项目，处理不同的，细胞内空间动力学的方面，但他们依赖于新的，尖端的光学，生物信息学和建模方法。这三家公司都在寻求开辟新的调查渠道，因此会带来不小的技术风险。我们认为，在这样一个知之甚少但极其重要的领域，发现和理解的预期收益证明了这些风险是合理的。

SPATIAL CONTROL OF INTRACELLULAR SIGNALING (Lee Bardwell, Theme Leader) | Some of the greatest mysteries in biological spafial dynamics lie at the subcellular level. The successes of biochemical and reconstitution-based assays in explaining fundamental mechanisms of cell biology have madeit easy to lose sight of the fact that cells are not just bags of well-sfirred enzymes. With respect to intracellular signaling pathways, there is growing evidence that spatial control is crucial to normal function [192-194] and occurs at many scales: compartments (plasma memtjrane, nucleus); sub-compartments (e.g. membrane rafts and nuclear speckles) and, below these levels, the nano-spafial scale, defined by local tethering interactions. Such spatial regulation is necessarily dynamic: scaffold proteins move to the plasma membrane, kinases and transcription factors move into or out of the nucleus, tethering interactions are regulated by phosphorylation, etc. In addifion, motor-based transport is used both to construct compartments, and to transport signaling molecules during sfimulafion; in turn this transport is regulated by extra- and intracellular cues. Yet for all the evidence that space matters, we often know less about spatial dynamics inside cells than outside of them. We propose three projects that deal with distinct,aspects of intracellular spatial dynamics, but are linked by their reliance on novel, cutting-edge optical, bioinformatic, and modeling methodologies. All three seek to open new lines of inquiry and, as such, incur more than a little technical risk. We believe the risks are justified by the expected gains in discovery and understanding in such a pooriy understood, yet extremely important, area.