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

细胞内信号的空间控制(Lee Bardwell，主题领导者) 生物空间动力学中一些最大的谜团存在于亚细胞水平。在解释细胞生物学的基本机制方面，基于生化和重组的分析取得了成功，这使得人们很容易忽视这样一个事实，即细胞不仅仅是一袋袋坚硬的酶。关于细胞内信号通路，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：隔室(质膜、核)；亚隔室(如膜筏和核斑点)，以及在这些水平以下的纳米尺度，由局部系留相互作用定义。 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，基于运动的运输既用于构建隔室，也用于在sfimulafion过程中运输信号分子；反过来，这种运输受到细胞外和细胞内信号的调节。然而，对于所有的 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，分别处理细胞内空间动力学的不同方面，但由于依赖于新颖的、尖端的光学、生物信息学和建模方法而联系在一起。这三家公司都寻求开辟新的调查渠道，因此招致了不少技术风险。我们相信，在这样一个被理解但极其重要的贫穷领域，在发现和理解方面取得的预期收益，是有理由冒风险的。

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.