Targeting DNA G4 to investigate ageing biology

靶向 DNA G4 研究衰老生物学

• 批准号: 2282303
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2282303
• 关键词: Targeting; DNA; G4; investigate; ageing

G-quadruplexes are DNA and RNA secondary structures that can form in the human genome and transcriptome. Small-molecules and chemical-biology tools to probe G-quadruplexes structures in cells have been developed over the past decade, but most of this strategies provide a stabilisation of these structure rather than their unfolding. Inducing G-quadruplex unfolding by means of chemical-biology approaches has great potential for therapeutic intervention towards rare genetic diseases like Cockayne Syndrome and ALS, which are both caused by an uncontrolled cellular accumulation of G-quadruplex structures. Souro's project is focused on investigating the application of short chemically-modified antisense oligonucleotides to achieve G-quadruplex destabilisation and unfolding. Although, his main project is focused on the fundamental biophysical understanding of how antisense-targeting approaches can be used to achieve thermodynamic and kinetic destabilisation of G-quadruplex structures, the knowledge generated during this PhD project will be of high relevance to investigate the potential of antisense strategies to treat ALS and Cockayne Syndrome by means of G-quadruplex destabilisation.

G-四联体是DNA和RNA的二级结构，可以在人类基因组和转录组中形成。在过去的十年里，用于探测细胞中G-四链体结构的小分子和化学生物学工具已经开发出来，但大多数这种策略提供的是这些结构的稳定，而不是它们的展开。通过化学-生物学方法诱导G-四链展开，对于治疗罕见的遗传性疾病如Cockayne综合征和ALS具有巨大的潜力，这两种疾病都是由G-四链结构的失控细胞积聚引起的。Souro的项目重点是研究短的化学修饰的反义寡核苷酸的应用，以实现G-四链的不稳定和展开。尽管他的主要项目集中在如何使用反义靶向方法来实现G-四链结构的热力学和动力学不稳定的基本生物物理理解上，但在这个博士项目期间产生的知识将对研究通过G-四链不稳定来治疗ALS和Cockayne综合征的反义策略的可能性具有很高的相关性。

项目成果

Chemical-biology approaches to probe DNA and RNA G-quadruplex structures in the genome

• DOI: 10.1039/c9cc09107f
• 发表时间: 2020-01-28
• 期刊: CHEMICAL COMMUNICATIONS
• 影响因子: 4.9
• 作者: Raguseo, Federica;Chowdhury, Souroprobho;Di Antonio, Marco
• 通讯作者: Di Antonio, Marco