Project 1 - Directional Sensing

使用荧光报告的实验表明，随着化学引诱剂cAMP浓度的变化，许多信号通路成分的空间分布发生了变化。这些变化发生在配体与受体结合或解除结合后的第一个0-10秒。在这段时间内，离cAMP源最近的膜上某些信号成分增加，而远离cAMP源的膜上其他成分浓度增加。尽管已经确定了大量的信号成分，但方向感应的确切机制仍然不清楚。为了充分了解这些机制，必须使用精确控制的刺激获得定量数据。为了解决这些机制，我们建议使用一种方法来研究趋化过程的初始阶段，在这种方法中，趋化剂刺激可以在空间和时间上得到仔细控制。这些实验的结果将被整合到模型中，进而指导实验。我们相信这种模型与实验的相互作用对于理解真核生物趋化性取得进展至关重要。事实上，正是这种互动在过去4年里取得了丰硕成果。

Experiments using fluorescent reporters have shown that the spatial distribution of many signaling pathway components is altered following a change in the chemoattractant cAMP concentration. These changes occur during the first 0-10 sec after binding or unbinding of the ligand to the receptors. Within this time frame, the membrane closest to the cAMP source experiences an increase in certain signaling components while other components display an increased concentration at the membrane away from the source. Even though a large number of signaling components have been identified, the precise mechanisms of directional sensing remain unclear. To fully understand these mechanisms it is essential to obtain quantitative data using precisely controlled stimulations. To address these mechanisms, we propose to investigate the initial phase of the chemotaxis process using an approach in which the chemoattractant stimulus can be carefully controlled, both spatially and temporally. The results from these experiments will be integrated into models that, in turn, will guide the experiments. We believe that such interaction of modeling with experimentation is essential for making progress in understanding eukaryotic chemotaxis. Indeed, it is this interaction that has proven to be fruitful during the past 4 years.