GREAT: Genome Refactoring and Engineering Approach to study non-coding genes driving Translation

伟大：研究驱动翻译的非编码基因的基因组重构和工程方法

• 批准号: EP/Y024753/1
• 负责人: Yizhi Cai
• 金额: $ 215.83万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY024753%2F1
• 关键词: GREAT; Genome; Refactoring; Engineering; Approach

Despite advances in genome-editing and functional genomics tecDespite advances in genome-editing and functional genomicstechnologies enhancing our ability to characterise genetic loci, systematic functional studies of genomic features have thus far beenlimited to existing natural genomes. As such, vast background genomic variation introduces noise and clouds discovery.Subsequently, our understanding of the largely underexplored, yet integral, such as non-coding RNAs (ncRNAs), would berevolutionised by the radical approach of synthetic genomics.The synthetic yeast (Sc2.0) genome provides an invaluable technology and resource for probing the nuanced roles of these geneticelements. Harnessing this new resource and technology, the work described in this proposal aims to elucidate important aspects oftRNA and rRNA biology through an engineering biology approach. Our motivation is to explore three fundamental aspects of ncRNAbiology: ncRNA organisation, regulation, and evolution. Our vision for this proposal is to unravel genomic fundamentals, removebiological complexity and redundancies, and ultimately couple evolution with engineering to optimise translation processes. Ourapproach will radically reorganise the genome, providing a unique opportunity to carry out three inter-linked work packages tosystematically study the organisation, regulation, and evolution of tRNAs and rRNAs. The steps towards the overarching goal are eachsignificant and substantial, and most importantly, complementary to each other.This proposal will thereby expand state-of-the-art synthetic genomics approaches established in our lab, to overcome the limitationsassociated with directly assaying currently intractable biological questions regarding ncRNA biology and molecular evolution. In thelong-term, since yeast is a safe and tractable model organism, this project will shed new light on genome fundamentals, but alsopotentially have profound impacts on medicine and biotechnologies.

尽管基因组编辑和功能基因组学技术取得了进展，但基因组特征的系统功能研究迄今为止仅限于现有的自然基因组。因此，巨大的背景基因组变异引入了噪音和云发现。随后，我们对很大程度上尚未充分探索但不可或缺的部分的理解，例如非编码RNA（ncRNA），将通过合成基因组学的激进方法而发生革命性的变化。合成酵母（Sc2） .0）基因组为探索这些遗传元件的微妙作用提供了宝贵的技术和资源。利用这一新资源和技术，本提案中描述的工作旨在通过工程生物学方法阐明 tRNA 和 rRNA 生物学的重要方面。我们的动机是探索 ncRNA 生物学的三个基本方面：ncRNA 组织、调控和进化。我们对该提案的愿景是阐明基因组基础知识，消除生物学复杂性和冗余，并最终将进化与工程结合起来以优化翻译过程。我们的方法将从根本上重组基因组，提供独特的机会来开展三个相互关联的工作包，以系统地研究 tRNA 和 rRNA 的组织、调控和进化。实现总体目标的步骤都是重要且实质性的，最重要的是，彼此相辅相成。因此，该提案将扩展我们实验室建立的最先进的合成基因组学方法，以克服与直接测定当前棘手的生物基因组学相关的限制。有关 ncRNA 生物学和分子进化的问题。从长远来看，由于酵母是一种安全且易于处理的模式生物，该项目将为基因组基础提供新的启示，而且还可能对医学和生物技术产生深远的影响。