Elucidating the regulation of signal transduction by polyadenylation

阐明多聚腺苷酸化对信号转导的调节

• 批准号: 2074538
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2074538
• 关键词: Elucidating; regulation; signal; transduction; polyadenylation

The surprising finding that RNA polyadenylation is upstream of the activation of the PI3K/mTOR pathway suggests that there either is a role for polyadenyation factors in this pathway, or there is an unknown polyadenylated RNA involved in its regulation. Either finding would be fundamentally novel and potentially lead to new anti-inflammatory or anti-cancer drugs. In this project you will use genetic manipulation of cell lines, including siRNA transfection, CRISPR-Cas9 knockout and recombination of genes and overexpression of wild type and mutant proteins to characterise the pathways involved in the regulation of signal transduction by polyadenylation. You will prepare samples for proteomics and RNAseq analysis and use bioinformatics analysis to interpret these genome-wide data. This work will contribute to the development of polyadenylation inhibitors as medicines. Indeed, the polyadenylation inhibitor cordycepin is showing promise in the treatment of breast cancer in mice.

RNA多聚腺苷酸化在PI 3 K/mTOR通路激活的上游这一令人惊讶的发现表明，在该通路中存在多聚腺苷酸化因子的作用，或者存在未知的多聚腺苷酸化RNA参与其调节。这两项发现都是全新的，并有可能导致新的抗炎或抗癌药物。在本项目中，您将使用细胞系的遗传操作，包括SiRNA转染、CRISPR-Cas9敲除和基因重组以及野生型和突变蛋白的过表达，以表征参与多聚腺苷酸化调节信号转导的途径。您将准备用于蛋白质组学和RNAseq分析的样品，并使用生物信息学分析来解释这些全基因组数据。这一工作将有助于多聚腺苷酸化抑制剂作为药物的开发。事实上，多聚腺苷酸化抑制剂虫草素在治疗小鼠乳腺癌方面显示出了希望。