A systems approach to understand the origin of transcriptional bursting

理解转录爆发起源的系统方法

• 批准号: 1897782
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1897782
• 关键词: systems; approach; understand; origin; transcriptional

Genetically identical cells, in identical environments often behave very differently to each other. This is clearly evident in transcription which often has large variations of mRNA in that are found in individual cells. This transcriptional noise is poorly understood, especially in mammalian cells. Understanding, and controlling this noise is of great interest to synthetic biology as this noise makes synthetic genetic networks unpredictable and unreliable.Of particular interest is the phenomena of transcriptional bursting, this is when a gene switches between an 'off' state and an 'on' state, where transcription only occurs in the 'on' state. This results in bursts of expression of a gene. My research will address the question - what is the origin of transcriptional bursting?This research will answer the question by combining imaging, genetic engineering, high throughput sequencing, bioinformatics and model fitting. More specifically; by perturbing interactions between the promotor and the 3' ends of genes and perturbing mediator/RNA polymerase II condensates.The projected outcomes of this project would be a significant advance in our understanding of transcriptional variability in mammalian cells, in particular how DNA interactions and polymerase condensates influence this. The project will also provide new ways to control biological noise, vital knowledge for synthetic biology applications.

基因相同的细胞，在相同的环境中，往往表现得非常不同。这在转录中是明显的，其通常具有在单个细胞中发现的mRNA的大的变化。这种转录噪音知之甚少，特别是在哺乳动物细胞中。理解和控制这种噪音是合成生物学的一大兴趣，因为这种噪音使合成基因网络变得不可预测和不可靠。特别感兴趣的是转录爆发现象，这是当基因在"关闭“状态和"打开"状态之间切换时，转录只发生在”打开“状态。这导致基因表达的爆发。我的研究将解决这个问题-什么是转录爆发的起源？本研究将结合影像学、基因工程、高通量测序、生物信息学和模型拟合来回答这个问题。更具体地说，通过干扰启动子和基因3'端之间的相互作用和干扰介体/RNA聚合酶II缩合物，该项目的预期结果将是我们对哺乳动物细胞转录变异性的理解的重大进展，特别是DNA相互作用和聚合酶缩合物如何影响这一点。该项目还将提供控制生物噪声的新方法，这是合成生物学应用的重要知识。

项目成果

Anti-bias training for (sc)RNA-seq: experimental and computational approaches to improve precision.

• DOI: 10.1093/bib/bbab148
• 发表时间: 2021-11-05
• 期刊: Briefings in bioinformatics
• 影响因子: 9.5
• 作者: Davies P;Jones M;Liu J;Hebenstreit D
• 通讯作者: Hebenstreit D

Non-coding RNAs Associated with Prader-Willi Syndrome Regulate Transcription of Neurodevelopmental Genes in Human Induced Pluripotent Stem Cells

与普瑞德-威利综合征相关的非编码 RNA 调节人诱导多能干细胞中神经发育基因的转录

• DOI: 10.1101/2021.05.11.443612
• 发表时间: 2021
• 作者: Sledziowska M

3 (')-5 (') crosstalk contributes to transcriptional bursting.

3（'）-5（'）串扰有助于转录爆发。

• DOI: 10.1186/s13059-020-02227-5
• 发表时间: 2021-02-04
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Cavallaro M;Walsh MD;Jones M;Teahan J;Tiberi S;Finkenstädt B;Hebenstreit D
• 通讯作者: Hebenstreit D

RPRD Proteins Control Transcription in Human Cells

• DOI: 10.1101/2021.06.20.449126
• 发表时间: 2021-06
• 期刊: bioRxiv
• 作者: Kinga Winczura;Hurmuz Ceylan;M. Sledziowska;Matt Jones;Holly Fagarasan;Jianming Wang;Marco Saponaro;R. Arnold;D. Hebenstreit;Pawel Grzechnik