The role of cell type specific DNA methylation at the interface between genetics and gene expression in Idiopathic Pulmonary Fibrosis (IPF)

特发性肺纤维化(IPF)是一种进行性肺部疾病，无法治愈。英国每年有5000人死于肺间质纤维化。基因变化使人们对IPF易感。基因变化如何影响身体的所有细胞，如何与只有肺部某些细胞出现问题的生物过程联系在一起，目前尚不清楚。我们认为，一种称为DNA甲基化的过程，已知对产生不同类型的细胞至关重要，提供了我们的遗传密码和细胞特定疾病变化之间的联系。更好地了解IPF中的DNA甲基化将通过增加对疾病和治疗目标的了解而为患者带来好处。这个项目的主要目的是利用尖端技术和监督团队的专家支持来识别和了解DNA甲基化、IPF感兴趣的DNA区域及其与基因表达和细胞功能的联系中的细胞类型差异。学生将学习基本技术，包括细胞培养和分子细胞生物学，R中的转录、基因组和表观基因组分析，以及特定细胞类型图谱技术的方法开发，包括激光捕获显微解剖和从福尔马林固定的组织中进行单核亚硫酸盐测序。该项目包括跨学院学习，包括诺丁汉大学、莱斯特大学和阿德莱德大学。

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no cure. Each year 5000 people in the UK die of IPF. Genetic changes make people susceptible to IPF. How genetic changes affecting all cells of the body, link to biological processes going wrong in only certain cells of the lung is unknown. We think a process called DNA methylation, known to be crucial for generating different cell types, provides the link between our genetic code and cell specific disease changes. Better understanding of DNA methylation in IPF will provide patient benefit via increased understanding of disease and treatment targets. The key aim of this project is to use cutting-edge technologies and the expert support of the supervisory team to identify and understand cell type differences in DNA methylation, in DNA regions of interest in IPF, and their link to gene expression and cell function. The student will learn fundamental techniques including cell culture and molecular cell biology, transcriptomic, genomic and epigenomic analysis in R, and method development of cell type-specific profiling techniques including laser capture microdissection and single nuclear bisulphite sequencing from formalin fixed tissue. The project includes cross institute learning, including the University of Nottingham, Leicester, and Adelaide.