Optimising the treatment of inflammation by targeting the phosphorylation of tristetraprolin: a combined experimental and mathematical modelling appro

通过靶向三四脯氨酸磷酸化优化炎症治疗：实验和数学建模相结合的方法

• 批准号: 2889903
• 金额: --
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2889903
• 关键词: Optimising; treatment; inflammation; targeting; phosphorylation

Resolution of inflammation refers to a process in which cells of the immune system cease to produce pro-inflammatory factors, and return to a resting state. This requires not only a halt to the transcription of pro-inflammatory genes, but also the destruction of pre-existing pro-inflammatory mRNAs - otherwise those pre-existing mRNAs would continue to be translated and inflammation would be sustained. Dynamic regulation of the stability of pro-inflammatory mRNAs is critical for correct timing of both the initiation and resolution phases of inflammatory responses, and chronic inflammatory diseases are characterised by defects in the resolution phase. The mitogen-activated protein kinase (MAPK) p38 pathway has a key role in this dynamic regulation of mRNA stability, controlling both the on- and off-phases of inflammatory gene expression by regulating the expression and activity of a selective mRNA-destabilising protein called tristetraprolin (TTP). In this PhD project we will use a combination of experimental approaches with mathematical modelling to understand how MAPK p38 regulates programmes of inflammatory gene expression via TTP. The ultimate goal is to identify new methods of treatment of inflammatory diseases.

炎症的分辨率是指免疫系统细胞不再产生促炎性因子并恢复静止状态的过程。这不仅需要停止促炎基因的转录，而且还需要销毁前现有的促炎性mRNA-否则，那些预先存在的mRNA将继续被翻译，并将持续炎症。促炎性mRNA稳定性的动态调节对于正确的时间和分辨率反应的启动和分辨率阶段至关重要，而慢性炎症性疾病的特征是在分辨率阶段的缺陷。有丝分裂原激活的蛋白激酶（MAPK）p38途径在mRNA稳定性的动态调节中具有关键作用，从而通过调节称为Tristetraprolin（TTP）的选择性mRNA-DESTABILISE蛋白的表达和活性来控制炎症基因表达的对炎症基因表达的影响和活性。在这个博士学位项目中，我们将使用实验方法与数学建模的组合来了解MAPK p38如何通过TTP调节炎症基因表达的程序。最终目标是确定炎症性疾病治疗的新方法。