FUTUREFISH: The role of circadian rhythms, immunity and infection in enhancing aquaculture

全球对鱼类的需求迅速增加，但传统捕捞渔业停滞不前和崩溃，因此必须扩大和强化水产养殖(养鱼)以满足需求。目前，水产养殖业发展的主要障碍是疾病；造成毁灭性的经济损失，并增加对药物干预的依赖。室内养鱼为水产养殖的集约化提供了希望；精细控制环境条件，在不侵蚀自然水生栖息地的情况下最大限度地提高鱼类产量。然而，尽管室内水产养殖经常使用人工光照制度(延长日长或甚至连续光照)来改善饲养，但这种方法如何导致疾病问题尚不清楚。在所有形式的生命中，从微生物到人类，生物体在生物过程中表现出每日的周期，如行为和新陈代谢，称为昼夜节律。昼夜节律通常由“时钟”基因的表达模式(开启和关闭)控制；这一系统通常被称为分子生物钟。分子钟可以改变或“携带”到光的条件下。生物钟和昼夜节律对免疫系统的功能很重要；哺乳动物的免疫细胞水平和抵抗感染的能力因时间而异。此外，昼夜节律的紊乱(如轮班工作、时差反应)会增加人类疾病的易感性或严重程度。因此，鱼类免疫昼夜节律的特征和光照制度如何影响鱼类抗病能力的研究对于未来水产养殖方法的可持续改进至关重要。此外，虽然众所周知，寄生虫也表现出每日的节律，但我们还不知道它们的分子生物钟的性质。因此，为了充分了解宿主和它们的病原体之间的日常相互作用，无论是鱼类还是其他动物，我们还必须考虑对寄生虫节律性的控制。在加的夫大学工作，汇聚鱼类寄生虫学、无脊椎动物遗传学和微生物群落的世界领先者，并与阿伯里斯特威斯大学的分子钟专家合作，我将解决鱼与寄生虫相互作用的昼夜生物学中的这些关键知识空白。我将测量三种具有重要经济意义的寄生虫(Arguus；淡水虱，Gryodactylus；皮虫，Saprolegnia；水霉菌)对虹鱼生物钟和免疫基因表达的昼夜节律的影响，并确定光照制度如何改变鲑鱼对感染的敏感性。据预测，长时间和/或持续的光周期会增加疾病的易感性。此外，我将量化基因表达的昼夜节律，并将研究结果与寄生虫活动和感染能力的测量相结合。我假设与寄生虫感染能力相关的关键基因的节律性，加上宿主免疫水平的每日变化，驱动寄生虫生存和在宿主上的行为的昼夜节律。最后，我将确定鲑鱼皮肤的微生物群(细菌群落)是否表现出昼夜节律，并检查通过抗生素治疗的扰动如何影响皮肤的微生物组成和随后对寄生虫的敏感性。据预测，由于抗生素导致有益皮肤微生物的变异减少，将增加对寄生虫的易感性。在水产养殖中，利用最佳昼夜节律的力量可以改善健康并减少抗菌剂的使用。综上所述，这项研究的结果将为指导养鱼场管理实践提供重要的新见解，并从根本上促进对寄生虫与其宿主之间日常互动的理解。

There is a rapidly increasing global demand for fish, yet stagnation and collapse of traditional capture fisheries, therefore aquaculture (fish farming) must be expanded and intensified to meet demand. Currently, the principal barrier to aquaculture development is disease; causing devastating economic losses and increasing reliance on drug interventions. Indoor fish farming provides hope for intensification of aquaculture; finely controlling environmental conditions to maximise fish production without encroaching on natural aquatic habitats. However, while manipulated light regimes (extended day lengths or even continuous light) are often used in indoor aquaculture to improve rearing, it is unknown how such approaches contribute to disease issues. Across all forms of life; from microbes to humans, organisms exhibit daily cycles in biological processes such as behaviour and metabolism, known as circadian rhythms. Circadian rhythms are typically controlled by expression patterns (turning on and off) of "clock" genes; a system often referred to as the molecular body clock. Molecular clocks can be altered or "entrained" to light conditions. Body clocks and circadian rhythms are important to immune system functioning; levels of immune cells and the ability to fight infection varies by time of day in mammals. Moreover, disruption of circadian rhythms (e.g. shift-work, jet-lag) can increase susceptibility to or severity of disease in humans. Therefore, the characterisation of fish circadian rhythms of immunity and the examination of how light regimes affect fish disease resistance is vital to future sustainable improvement of aquaculture methods. In addition, although it is well known that parasites too exhibit daily rhythms, we do not yet know the nature of their molecular body clocks. Therefore, to fully understand the daily interplay between hosts and their pathogens, be it fish or other animals, we must also consider the control of rhythmicity in parasites.Working at Cardiff University, bringing together world leaders in fish parasitology, invertebrate genetics, and microbial communities, and in collaboration with experts in molecular clocks at Aberystwyth University, I will address these key knowledge gaps in the circadian biology of fish-parasite interactions. I will measure the impact of three economically-important parasites (Argulus; freshwater louse, Gryodactylus; skin worm, Saprolegnia; water mould) on rainbow trout circadian rhythms of clock and immune gene expression, and determine how light regimes alter the susceptibility of trout to infection. It is predicted extended and/or constant photoperiods increase susceptibility to disease. In addition, I will quantify the circadian rhythms of gene expression in Gyrodactylus and couple the findings with measures of parasite activity and infection ability. I hypothesise rhythmicity of key genes related to parasite infection ability, coupled with daily variations in host immune levels, drive circadian rhythms in parasite survival and behaviour on-host. Finally, I will determine whether the microbiome (bacteria community) of trout skin exhibits circadian rhythmicity and examine how perturbation, via antibiotic treatment, impacts the skin's microbial composition and subsequent susceptibility to parasites. It is predicted reduced variation in beneficial skin microbes due to antibiotics will increase susceptibility to parasites. Harnessing the power of optimal circadian rhythms can improve health and reduce antimicrobial usage in aquaculture. Taken together, the results of this fellowship will provide important new insights to inform fish farm management practices and fundamentally advance the understanding of daily interactions between parasites and their hosts.