Dissecting the role of Hedgehog signalling during development, regeneration and ageing in vivo using novel phosphorescent small molecules

使用新型磷光小分子剖析 Hedgehog 信号在体内发育、再生和衰老过程中的作用

• 批准号: 1949661
• 金额: --
• 依托单位: University of St Andrews
• 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-1949661
• 关键词: Dissecting; role; Hedgehog; signalling; during

The goal of this PhD project is to study the changing roles of Hedgehog signalling during amphioxus' entire lifespan, from embryonic development to adult regeneration, using novel phosphorescent compounds. The primary aims include: 1. to characterise phenotypes resulting from treatment of chemical compounds affecting Hedgehog signalling via immunohistochemistry and whole mount in situ hybridisation 2. to generate novel iridium tagged compounds that can be used to image the Hh signalling pathway. The current way of imaging (immunofluorescence) has the following limitations: it is hard to quantify, most cells and organisms naturally autofluoresce which makes specific fluorescent labels hard to visualise, and they are issues with using them to image live organisms. The novel iridium tagged compound we plan to create needs to be the following: water soluble and biocompatible (to allow in vivo imaging). We are planning on using a phosphorescent cationic iridium(III) complex and we hope to develop this further to create a colour palette.3. to generate novel iridium tagged compounds with photoconvertible properties in order to modulate spatial and temporal activity of the biomolecules. Amphioxus is the model organism used for this project due to the following: it shares many similarities with vertebrates but has a simpler genome and anatomy (making the Hedgehog signalling pathway easier to study), it is semi-translucent (aids live imaging), it regenerates well and being an invertebrate chordate makes it a great ethical alternative to adult regeneration research in vertebrates. This project has clinical applications due to the Hedgehog signalling pathway having links to neural defects, skeletal defects, cyclopia, cancer and ciliopathies. In addition, the study of regeneration is closely linked to wound healing so can help our understanding of hedgehog signalling in both regeneration and wound healing.

该博士项目的目标是利用新型磷光化合物研究刺猬信号在文昌鱼整个生命周期（从胚胎发育到成体再生）中的作用变化。主要目标包括： 1. 通过免疫组织化学和整体原位杂交来表征影响 Hedgehog 信号传导的化合物处理所产生的表型 2. 生成可用于对 Hh 信号传导途径进行成像的新型铱标记化合物。目前的成像方式（免疫荧光）具有以下局限性：难以量化，大多数细胞和生物体自然自发荧光，这使得特定的荧光标记难以可视化，并且使用它们对活体生物体进行成像存在问题。我们计划创建的新型铱标记化合物需要满足以下条件：水溶性和生物相容性（以允许体内成像）。我们计划使用磷光阳离子铱（III）络合物，并希望进一步开发它以创建调色板。3。生成具有光转换特性的新型铱标记化合物，以调节生物分子的空间和时间活性。文昌鱼是该项目使用的模式生物，原因如下：它与脊椎动物有许多相似之处，但具有更简单的基因组和解剖结构（使刺猬信号通路更容易研究），它是半透明的（有助于实时成像），它再生良好，并且作为无脊椎动物脊索动物，使其成为脊椎动物成体再生研究的一个很好的道德替代方案。该项目具有临床应用价值，因为 Hedgehog 信号通路与神经缺陷、骨骼缺陷、独眼、癌症和纤毛病有关。此外，再生研究与伤口愈合密切相关，因此可以帮助我们了解再生和伤口愈合中的刺猬信号传导。