Mechanisms of molecular recogntition by chromatin regulatory proteins

我们对生命系统的理解中的一个主要差距是细胞中的单个分子如何相互通信，以创建一个动态的，复制的系统，以响应其环境。控制数千种不同蛋白质分子如何相互作用以及与细胞的DNA（基因）相互作用以控制其生长，环境反应和复制的原理仍在阐明中。我们的长期研究计划旨在通过使用先进的分析方法来阐明这些基本机制，以可视化蛋白质如何识别彼此以及我们基因的特定部分。我们的短期和中期目标是表征几个关键的多蛋白质复合物的组装和调节，这些复合物识别并与我们基因上的“化学标签”相互作用，以打开或关闭它们。细胞中基因上的各种化学标签有助于建立特定的细胞类型-例如动物或人类的皮肤细胞与肌肉细胞。这些标签也为细胞提供了一种方法，当细胞在生长过程中一分为二时，它可以“记住”它是什么类型的细胞。 通过“观察”蛋白质如何相互作用以及与这些化学标签的相互作用，我们可以更深入地了解细胞如何工作，以及我们如何潜在地操纵它们。最终，这项工作将使人们能够更全面地了解细胞信号网络、大分子识别以及如何将这些知识用于生物技术、化学和医学。

One of the major gaps in our understanding of living systems is how individual molecules in cells communicate with one another to create a dynamic, replicating system that responds to its environment. The principles that govern how the thousands of different protein molecules interact with one another and with the DNA (genes) of a cell to control its growth, environmental response and replication are still being elucidated. Our long-term research program seeks to elucidate these fundamental mechanisms by using advanced analytical methods to visualize how proteins recognize one another and specific parts of our genes. Our short and medium term goals are to characterize the assembly and regulation of several key multi-protein complexes that recognize and interact with ‘chemical tags’ on our genes to turn them on or off. The various chemical tags on genes in cells help establish the specific cell type – for example a skin cell versus a muscle cell in animals or humans. These tags also provide a way for a cell to ‘remember’ what type of cell it is when it divides in two during cell growth. By ‘seeing’ how proteins interact with one another and with these chemical tags we can understand more deeply how cells work, and how we could potentially manipulate them. Ultimately this work will enable a fuller understanding of cellular signaling networks, macromolecular recognition, and how this knowledge can be engineered or harnessed for biotechnology, chemistry and medicine.