Project 1 - Directional Sensing

使用荧光报告分子的实验表明，许多信号传导途径组分的空间分布随着化学引诱物cAMP浓度的变化而改变。这些变化发生在配体与受体结合或不结合后的前0-10秒。在该时间范围内，最接近cAMP源的膜经历某些信号传导组分的增加，而其他组分在远离源的膜处显示出增加的浓度。尽管已经确定了大量的信号成分，但方向感测的精确机制仍然不清楚。为了充分理解这些机制，必须使用精确控制的刺激来获得定量数据。为了解决这些机制，我们建议调查的初始阶段的趋化过程中使用的方法，在该方法中，化学引诱刺激可以仔细控制，空间和时间。这些实验的结果将被整合到模型中，反过来，这些模型将指导实验。我们相信，这种相互作用的建模与实验是必不可少的进展，了解真核细胞的趋化性。事实上，正是这种互动在过去四年中证明是富有成果的。

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.