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）是一种无法治愈的进行性肺部疾病。英国每年有5000人死于IPF。基因变化使人们容易患上IPF。基因变化如何影响身体的所有细胞，与生物过程中只有某些肺细胞出现问题有关，目前尚不清楚。我们认为，DNA甲基化的过程在我们的遗传密码和细胞特异性疾病变化之间提供了联系。众所周知，DNA甲基化对于产生不同的细胞类型至关重要。更好地了解IPF中的DNA甲基化将通过增加对疾病和治疗靶点的了解为患者提供益处。该项目的主要目标是利用尖端技术和监督团队的专家支持，识别和了解DNA甲基化的细胞类型差异，IPF中感兴趣的DNA区域，以及它们与基因表达和细胞功能的联系。学生将学习基本技术，包括细胞培养和分子细胞生物学，转录组学，基因组学和表观基因组学分析，以及细胞类型特异性分析技术的方法开发，包括激光捕获显微解剖和福尔马林固定组织的单核亚硫酸酯测序。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.