Project 1 - Directional Sensing

使用荧光记者的实验表明，随着化学诱导剂cAMP浓度的变化，许多信号通路组件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秒内。在这段时间内，最接近cAMP来源的细胞膜经历了某些信号成分的增加，而其他成分在远离来源的细胞膜上显示出更高的浓度。尽管已经确定了大量的信号成分，但定向感知的确切机制仍然不清楚。为了充分理解这些机制，使用精确控制的刺激获得定量数据是必不可少的。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，趋化刺激可以在空间和时间上被仔细控制。这些实验的结果将被整合到模型中，这些模型反过来将指导实验。我们认为，这种模拟和实验的相互作用对于理解真核细胞趋化作用是至关重要的。事实上，在过去的4年里，这种互动被证明是富有成效的。

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.