The Role of Intermediate Filaments in Inflammation

翻译后摘要：中间丝是高度保守的真核细胞骨架蛋白存在于 几乎是身体的每一个细胞。虽然最初认为只是为细胞提供结构支持， 中间丝现在涉及多种生物过程，这是由于它们 许多蛋白质相互作用。由于中间丝单体的数量，多于 70在人类中，其调控的复杂性，超过100翻译后修饰 虽然我们对这些基因调控的分子机制的理解仍存在差距， 并通过它促进许多生物过程。为了开始填补这些空白，我们寻求 以确定在细胞中调节中间丝的分子机制， 通过关注中间丝在中性粒细胞中的作用， 炎症过程和迁移。这一建议建立在方案执行主任以往经验的基础上 研究细菌感染过程中中间丝的功能， 新的永生化中性粒细胞群体的细胞模型， PI成功使用的方法定义了中间体 丝状波形蛋白有助于炎症过程。这提供的资金灵活性 R35计划将使PI能够灵活地遵循最有希望的研究路线 并利用所提出的方法在实验室内培训初级科学家。的 成功完成拟议的研究很可能会改善我们的一般 了解细胞中的生物学过程，中间纤维有助于 以及我们对中性粒细胞功能调节机制的理解， 炎症

Abstract: Intermediate filaments are highly conserved eukaryotic cytoskeletal proteins present in nearly every cell in the body. Although initially thought to simply provide structural support to cells, intermediate filaments are now implicated in a variety of biological processes due to their numerous protein interactions. Due to the number of intermediate filament monomers, more than 70 in humans, and the complexity of their regulation, more than 100 posttranslational modification sites, gaps remain in our understanding of the molecular mechanisms by which they are regulated and by which they contribute to many biological processes. To begin to fill these gaps, we seek to define molecular mechanisms by which intermediate filaments are regulated in cells and to define how intermediate filaments contribute to inflammation by focusing on their role in neutrophil inflammatory processes and migration. This proposal builds on the PIs previous experience investigating intermediate filament function during bacterial infection by proposing to leverage new cellular models of immortalized neutrophil populations with established screening approaches successfully use by the PI to define molecular mechanisms by which the intermediate filament vimentin contributes to inflammatory processes. The flexibility in funding provided by this R35 program will enable the PI the flexibility to follow the most promising lines of investigation and to leverage the proposed approaches to train junior scientists within the laboratory. The successful completion of the proposed studies is highly likely to improve our general understanding about the biological processes in cells to which intermediate filaments contribute and to our understanding of the mechanisms by which neutrophil function is regulated during inflammation.