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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、形式和功能在很大程度上是在发育的早期阶段建立的，并且涉及从鱼类到哺乳动物的不同脊椎动物群体中非常相似的过程。分子遗传学的进步使我们对这些基本发育过程如何工作以及它们在脊椎动物物种之间如何保守的知识急剧扩展。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易处理性-通过包括筛选在内的遗传方法定义基因功能的能力。在执行所谓的“正向遗传筛选”时，在整个基因组的基因中随机诱导突变，然后筛选确定这些突变中的哪些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找到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验概念。“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度，允许研究细胞运动，发展神经元连接，以及跟踪神经元活动，以响应活体动物中感知的刺激，而无需或只需最小的干预。这笔赠款提供资金的最先进的水族馆的新状态，以保持许多独特的鱼类线使用的许多研究人员在伦敦大学学院和超越。新的水族馆将使鱼类保持在一个孤立的，无疾病的环境，确保最佳的饲养条件，健康和繁殖性能的成鱼。新的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，到调查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的神经网络，以及视觉引导的行为，如狩猎。也许令人惊讶的是，即使是非常年轻的斑马鱼鱼苗也表现出社会偏好，因此我们可以研究这种类型的社会行为。在分子，成像和计算方法的进步，使我们能够研究在细胞分辨率的行为反应的神经基础，并确定参与接收感觉信息和那些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，包括解决上皮细胞如何形成和功能以及细胞在胚胎内迁移时如何表现。许多项目将得到上述遗传筛选的支持，这些筛选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使用动物的方法和途径。例如，我们的目标是确定个体鱼在胚胎时携带的基因缺陷，以便我们只培养那些我们特别需要用于实验的鱼。我们还将致力于改善动物饲养和护理程序，并评估饲养条件如何影响幼鱼的后续行为。