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A new aquarium for the UCL Fish Facility

伦敦大学学院鱼类设施的新水族馆

基本信息

批准号：
BB/R013705/1
负责人：
Stephen Wilson
金额：
$ 47.51万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR013705%2F1
关键词：
new aquarium UCL Fish Facility

项目摘要

The structures, forms and functions of the vertebrate body are largely established during the early stages of development and involve processes that are remarkably similar throughout the different vertebrate groups, from fish to mammals. Advances in molecular genetics have led to a dramatic expansion in our knowledge of how these fundamental developmental processes work and how conserved they are between vertebrate species. This expansion in our knowledge has been achieved largely by studying a limited number of model vertebrate organisms. The zebrafish is now one of the most widely used model systems in part because of its genetic tractability - the ability to define gene functions through genetic approaches including screens. In performing what is called a "forward genetic screen", mutations are randomly induced in genes throughout the genome and then screens identify which of these mutations affect the developmental process under study. This approach gives a relatively unbiased way to find the genes required for specific developmental processes. An alternative "reverse genetic" approach is to "knock-out" the activity of genes that might be involved in the process of interest, and relies on some prior notion of the likely function of the gene. Both 'forward' and 'reverse' genetic approaches are feasible in fish and are being used to study many aspects of development, organ function and neurobiology. Another major advantage of zebrafish is its optical transparency allowing investigations into cell movements, developing neuronal connections, as well as tracking neuronal activity in response to perceived stimuli in the living animal with no or only minimal intervention. This grant provides funds a new state of the art aquarium to maintain many distinct lines of fish used by many researchers at UCL and beyond. The new aquarium will enable fish to be maintained in an isolated, disease-free environment ensuring optimal rearing conditions, health and breeding performance from the adult fish. The new aquarium will support a wide range of research and animal welfare projects that use zebrafish as a model system. Several of the research teams that will use the aquarium study the processes by which the nervous system forms. Research ranges from study of the developmental mechanisms by which neurons are generated, acquire their identities and form connections to investigation of the resulting neural circuits that mediate behaviours. For instance, researchers are examining the neural networks underlying circadian rhythms and sleep, as well as visually guided behaviours such as hunting. Maybe surprisingly, even very young zebrafish fry exhibits social preference and so we can study this type of social behaviour. Advances in molecular, imaging and computational approaches allow us to study the neural basis of behavioural responses at cellular resolution and identify the specific neurons that are involved in receiving sensory information and those involved in eliciting behavioural responses. Other research teams are studying aspects of cell biology in living fish embryos including addressing how epithelia are formed and function and how cells behave as they migrate within the embryo. Many of the projects will be supported by the use of the genetic screens described above that help us to identify the key genes involved in the processes under study. We will also develop methods and approaches that help to reduce and refine the use of animals in research. For instance we aim to determine the gene defects carried by individual fish when they are embryos so that we only grow those fish we specifically need for experiments. We will also aim to improve animal husbandry and care procedures and assess how rearing conditions affect subsequent behaviours of the young fish.

脊椎动物身体的结构、形态和功能在很大程度上是在发育的早期阶段建立起来的，并且涉及的过程在不同的脊椎动物群体中非常相似，从鱼类到哺乳动物。分子遗传学的进步使我们对这些基本发育过程如何运作以及它们在脊椎动物物种之间的保守性的认识有了戏剧性的扩展。我们知识的扩展主要是通过研究有限数量的模式脊椎动物生物来实现的。斑马鱼现在是最广泛使用的模型系统之一，部分原因是它的遗传可追溯性——通过包括筛选在内的遗传方法定义基因功能的能力。在进行所谓的“正向基因筛选”时，突变是在整个基因组中随机诱导的，然后筛选确定哪些突变会影响所研究的发育过程。这种方法提供了一种相对公正的方法来寻找特定发育过程所需的基因。另一种“反向遗传”方法是“敲除”可能参与感兴趣过程的基因的活性，并依赖于对基因可能功能的一些先前概念。“正向”和“反向”遗传方法在鱼类中都是可行的，并被用于研究发育、器官功能和神经生物学的许多方面。斑马鱼的另一个主要优势是它的光学透明性，允许研究细胞运动，发展神经元连接，以及在没有或只有最小干预的情况下跟踪活动物感知刺激的神经元活动。这笔拨款为一个新的最先进的水族馆提供了资金，以维持伦敦大学学院和其他地方的许多研究人员使用的许多不同的鱼类。新的水族馆将使鱼类保持在一个隔离的、无疾病的环境中，确保最佳的饲养条件、健康和成年鱼的繁殖性能。新水族馆将支持广泛的研究和动物福利项目，使用斑马鱼作为模型系统。几个研究小组将使用水族馆来研究神经系统形成的过程。研究范围从研究神经元产生、获得其身份和形成连接的发育机制，到研究介导行为的神经回路。例如，研究人员正在研究昼夜节律和睡眠背后的神经网络，以及狩猎等视觉引导行为。也许令人惊讶的是，即使是非常年轻的斑马鱼苗也表现出社会偏好，所以我们可以研究这种社会行为。分子、成像和计算方法的进步使我们能够在细胞分辨率上研究行为反应的神经基础，并识别参与接收感觉信息和参与引发行为反应的特定神经元。其他研究小组正在研究活鱼胚胎的细胞生物学方面，包括研究上皮如何形成和功能，以及细胞在胚胎内迁移时的行为。许多项目将得到上述基因筛选的支持，这有助于我们识别参与研究过程的关键基因。我们还将开发有助于减少和改进研究中动物使用的方法和途径。例如，我们的目标是确定单个鱼在胚胎时携带的基因缺陷，以便我们只培养我们特别需要的实验鱼。我们还将致力于改善畜牧业和护理程序，并评估饲养条件如何影响幼鱼的后续行为。