microRNA regulation of virus gene expression

背景MicroRNA（miRNAs）是一类在转录后水平调控基因表达的短链非编码RNA。miRNA在调节多种生物学过程中发挥核心作用，因此miRNA表达的失调与许多人类疾病有关。我们有令人兴奋的初步数据，使用miRNA分析，表明宿主miRNA表达可以在KSHV裂解复制周期中失调。因此，miRNA调控异常在介导病毒复制、发病机制和肿瘤发生中起关键作用。该项目的目的是确定病毒介导的宿主细胞miRNAs操作如何在病毒感染期间调节病毒和宿主细胞基因表达。此外，该项目有可能确定新的宿主细胞限制因子，防止疱疹病毒复制，突出了潜在的治疗方法，用于治疗这个重要的病毒家族。这个项目非常新颖。一个新兴的研究领域表明，操纵miRNA表达可以对宿主细胞基因表达产生根本性影响。因此，该项目将研究病毒用于调节宿主细胞基因表达的新机制，这些机制可以决定如何调节病毒和宿主细胞转录组以利于病毒复制。该项目是及时的，因为这是一个新兴的研究领域。miRNAs是基因表达的关键调节因子，miRNAs的异常表达越来越多地与人类疾病相关。该项目采用多学科方法和尖端方法，包括miRNA序列，生物信息学分析，成像和细胞生物学。

Background. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at a post-transcriptional level. miRNAs play a central role in regulating a wide variety of biological processes and as such dysregulation of miRNA expression has been implicated in many human diseases. We have exciting preliminary data, using miRNA profiling, suggesting that host miRNA expression can be dysregulated during the KSHV lytic replication cycle. Therefore, miRNA dysregulation contributes a key role in mediating viral replication, pathogenesis and tumourigenesis.Objectives. The aim of this project is to determine how virus-mediated manipulation of host cell miRNAs regulates both virus and host cell gene expression during virus infection. Moreover, the project has potential to identify novel host cell restriction factors which prevent herpesvirus replication, highlighting potential therapeutic approaches for the treatment of this important family of viruses.Novelty. This project is highly novel. An emerging area of research suggests that manipulation of miRNA expression can have fundamental effects on host cell gene expression. The project will therefore investigate novel mechanisms utilised by the virus to regulate host cell gene expression which can dictate how the virus and host cell transcriptome is regulated to benefit virus replication.Timeliness. The project is timely as this is an emerging area of research. miRNAs are key regulators of gene expression and aberrant expression of miRNAs is increasingly being associated with human disease.Experimental Approach. The project utilises a multidisiplinary approach and cutting-edge methodology including miRNA seq, bioinformatic analysis, imaging and cell biology.