There is more than meet the eye: reconstruction of isoform level regulatory networks in the human brain

不仅仅是表面上看得到的：人脑异构体水平调控网络的重建

• 批准号: 2748728
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2748728
• 关键词: There; more; than; meet; eye

Therapies for many potentially treatable genetic diseases remain out of touch because we still don't have a full picture of how genes are regulated differently between cells and tissues. Many genes, including some directly associated with traits and disorders, are widely expressed across cells and tissues, leading to potential unwanted secondary effects if blindly targeted with medications. However, nearly all genes in humans undergo alternative splicing, the process through which different transcripts are generated from a single gene.Recent work by us and others demonstrated that alternatively spliced transcripts arising from many of these genes tend to have a much more specific expression, opening the opportunity to identify specific isoforms as potential targets for drug development. To further the identification of isoforms of interest it is becoming increasingly important to fully characterise their regulation through the reconstruction of regulatory networks integrating splicing information in relevant tissues.The main aim of the project is to develop approaches to reconstruct regulatory networks at the transcript level in the human brain, assess the transcript regulation for candidate genes, and assess the impact of genetic variation on transcript regulation.

许多潜在可治疗的遗传疾病的疗法仍然失去联系，因为我们仍然对细胞和组织之间的基因如何不同。许多基因，包括与性状和疾病直接相关的一些基因，在细胞和组织中广泛表达，如果以药物为盲目的靶向，可能会导致潜在的不必要的次要作用。然而，人类几乎所有基因都经历了替代剪接，从单个基因产生不同的转录本的过程。我们和其他基因的工作表明，这些基因引起的剪接转录本往往具有更具体的表达，开放了将特定的同种型识别为药物发育的特定同源靶标。为了进一步识别感兴趣的同工型，通过重建监管网络将其整合在相关组织中的剪接信息整合剪接信息来充分表征其调节。该项目的主要目的是开发方法来重建调节性网络在人脑中转录水平上的调节网络，评估候选遗传学变异的转录物调节，并评估概括的变体。