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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，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是如何工作的，以及它们在脊椎动物物种之间的保守程度的了解有了戏剧性的扩展。我们知识的这种扩展在很大程度上是通过研究有限数量的脊椎动物模型实现的。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操纵性--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“正向基因筛查”时，在整个基因组的基因中随机诱导突变，然后筛查确定这些突变中的哪些会影响正在研究的发育过程。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，并依赖于对该基因可能功能的某种先验概念。“正向”和“反向”遗传方法在鱼类中都是可行的，正被用于研究发育、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，允许研究细胞运动，发展神经元连接，以及跟踪活着的动物对感知到的刺激做出反应的神经元活动，而不需要或只需要很少的干预。这笔赠款为一个新的艺术水族馆提供了资金，以维护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线。新的水族馆将使鱼类能够保持在一个与世隔绝的、没有疾病的环境中，确保成年鱼的最佳饲养条件、健康和繁殖性能。新的水族馆将支持一系列以斑马鱼为模型系统的研究和动物福利项目。几个将使用水族馆的研究团队研究神经系统形成的过程。研究的范围从研究神经元产生、获得其身份和形成联系的发育机制，到研究调节行为的结果神经回路。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鱼苗也表现出了社会偏好，所以我们可以研究这种类型的社会行为。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，包括研究上皮细胞是如何形成和功能的，以及细胞在胚胎内迁移时的行为。许多项目将通过使用上述基因筛查得到支持，这些筛查有助于我们确定正在研究的过程中涉及的关键基因。我们还将开发有助于减少和改进动物在研究中的使用的方法和途径。例如，我们的目标是确定每条鱼在胚胎时携带的基因缺陷，以便我们只培育那些我们特别需要用于实验的鱼。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随后的行为。