Understanding the mechanism of vision development.

了解视觉发育的机制。

• 批准号: 2737568
• 金额: --
• 依托单位: University of Leicester
• 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: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2737568
• 关键词: Understanding; mechanism; vision; development.

Retinal development is a dynamic process that begins in utero and continues postnatally up to the age of 13 years. Zebrafish are the best choice of model organism to study vision development due to multiple factors. Zebrafish retinal anatomy, development and physiological characteristics are like humans. By 72 hours post-fertilisation retinal morphology and function is robust like adults and testable using visual behaviour assays. In this project we will use CRISPR-Cas9 based techniques to manipulate genes that will modify the optokinetic reflex and correlate this to retinal structure and function in zebrafish. We will analyse summary statistics from Genome Wide Association Studies (GWAS) related to vision development to prioritise gene targets in zebrafish. In cases where paralogs are present, a double knockout strategy will be implemented to explore gene redundancies, as well as potential sub- or neo-functional aspects in zebrafish. Additionally, we will develop innovative visual behaviour analysis tools using deep learning techniques. These tools are designed to be versatile and applicable across various laboratory settings, allowing for stimulus and acquisition independence. Whilst previous work has demonstrated the use of the optokinetic reflex as a robust assay to measure visual behaviour, currently no reporting standards exist. We will systematically develop an optimal protocol for optokinetic reflex assay in zebrafish using range of different stimuli with the aim of creating reporting standards in this domain. This targeted approach will not only ensure novel methodological advances in the field but also improve our understanding on the mechanisms of normal vision development and associated gene regulatory networks.

视网膜发育是一个动态过程，从子宫内开始一直持续到出生后直至 13 岁。由于多种因素的影响，斑马鱼是研究视觉发育的模型生物的最佳选择。斑马鱼的视网膜解剖、发育和生理特征与人类相似。受精后 72 小时，视网膜形态和功能与成人一样健全，并且可以使用视觉行为测定进行测试。在这个项目中，我们将使用基于 CRISPR-Cas9 的技术来操纵基因，从而改变斑马鱼的视动反射并将其与视网膜结构和功能相关联。我们将分析与视觉发育相关的全基因组关联研究 (GWAS) 的汇总统计数据，以优先考虑斑马鱼的基因目标。在存在旁系同源物的情况下，将实施双敲除策略来探索斑马鱼的基因冗余以及潜在的亚功能或新功能方面。此外，我们将利用深度学习技术开发创新的视觉行为分析工具。这些工具的设计用途广泛，适用于各种实验室环境，从而实现刺激和采集的独立性。虽然之前的工作已经证明了使用视动反射作为测量视觉行为的可靠测定方法，但目前尚不存在报告标准。我们将使用一系列不同的刺激系统地开发斑马鱼视动反射测定的最佳方案，旨在创建该领域的报告标准。这种有针对性的方法不仅将确保该领域的新方法学进步，而且将提高我们对正常视力发育机制和相关基因调控网络的理解。