Mechanisms of molecular recogntition by chromatin regulatory proteins

染色质调节蛋白的分子识别机制

• 批准号: RGPIN-2015-05939
• 负责人: Arrowsmith, Cheryl
• 金额: $ 2.77万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613838
• 关键词: Mechanisms; molecular; recogntition; chromatin; regulatory

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.

我们对生命系统的理解的主要差距之一是细胞中的单个分子如何相互沟通，以创建一个动态的、复制的系统，对其环境做出反应。控制数以千计的不同蛋白质分子如何相互作用以及如何与细胞的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试图通过使用先进的分析方法来可视化蛋白质如何识别彼此和我们基因的特定部分来阐明这些基本机制。我们的短期和中期目标是确定几个关键的多蛋白复合体的组装和调控的特征，这些复合体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记有助于确定特定的细胞类型--例如，动物或人类的皮肤细胞与肌肉细胞。这些标签还为细胞提供了一种方法，当细胞在细胞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，以及如何与这些化学标签相互作用，我们可以更深入地了解细胞是如何工作的，以及我们可能如何操纵它们。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应用于生物技术、化学和医学。