Elucidating the role of host cell ncRNAs in viral replication

非编码RNA（ncRNA）是基因表达的关键调节因子，并且由于ncRNA在许多人类疾病中经常改变，因此强调其重要性。病毒已经进化出操纵宿主ncRNA以增强病毒基因表达并调节宿主对感染的反应的方法。然而，如何以及为什么ncRNA水平在感染过程中发生变化尚未完全阐明。本项目将研究病毒利用一种新的机制来失调最近发现的一组ncRNA，称为tRFs。该项目将阐明这种新出现的ncRNA物种是如何以及为什么被病毒改变的，并确定逆转这种失调是否可以作为一种新的抗病毒策略。该项目是高度新颖的，利用多学科方法和尖端方法，包括CLASH，RNA-IP，成像，细胞生物学和3D肿瘤模型。该项目将确定病毒操纵宿主细胞以增强其复制的新方法，并更好地了解ncRNA物种如何调节基因表达以及这如何影响人类疾病。此外，它可能为重要的人类病原体的治疗干预提供新的策略。

Non-coding RNAs (ncRNAs) are critical regulators of gene expression and their importance is emphasised as ncRNAs are frequently altered in many human diseases. Viruses have evolved ways to manipulate host ncRNAs to enhance virus gene expression and modulate the host response to infection. However, how and why ncRNA levels are altered during infection is yet to be fully elucidated.This project will investigate a novel mechanism utilised by viruses to dysregulate a recently identified group of ncRNAs, termed tRFs. The project will elucidate how and why this emerging ncRNA species are altered by the virus and also determine if reversing this dysregulation can be used as a novel antiviral strategy.The project is highly novel utilising a multidisciplinary approach and cutting-edge methodology including CLASH, RNA-IPs, imaging, cell biology and 3D tumour models.In summary, this project will identify novel ways viruses manipulate the host cell to enhance their replication and provide a better understanding of how ncRNA species can regulate gene expression and how this impacts on human disease. Moreover, it may provide new strategies for therapeutic interventions of important human pathogens.