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

全球对鱼类的需求迅速增加，但传统捕捞渔业陷入停滞和崩溃，因此必须扩大和加强水产养殖（鱼类养殖）以满足需求。目前，水产养殖发展的主要障碍是疾病；造成毁灭性的经济损失，增加对药物干预的依赖。室内养鱼为水产养殖集约化提供了希望；精细控制环境条件，在不侵犯天然水生生境的情况下，最大限度地提高鱼类产量。然而，虽然在室内水产养殖中经常使用操纵光照制度（延长日照长度或甚至连续光照）来改善饲养，但尚不清楚这种方法如何导致疾病问题。跨越所有形式的生命；从微生物到人类，生物体在行为和新陈代谢等生物过程中表现出每日周期，即昼夜节律。昼夜节律通常由“时钟”基因的表达模式（开启和关闭）控制；这个系统通常被称为分子生物钟。分子钟可以被改变或“夹带”到光照条件下。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抗感染能力因一天中的不同时间而异。此外，昼夜节律的紊乱（如倒班、倒时差）可增加人类对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性的研究对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，寄生虫也表现出日常节律，但我们还不知道它们的分子生物钟的性质。因此，为了充分了解宿主与其病原体（无论是鱼类还是其他动物）之间的日常相互作用，我们还必须考虑对寄生虫节律性的控制。在卡迪夫大学工作，汇集了鱼类寄生虫学，无脊椎动物遗传学和微生物群落的世界领导者，并与阿伯里斯特威斯大学的分子钟专家合作，我将解决鱼-寄生虫相互作用的昼夜节律生物学中的这些关键知识空白。我将测量三种经济上重要的寄生虫（Argulus；淡水虱，Gryodactylus；皮肤蠕虫，Saprolegnia；水霉菌）对虹鳟鱼生物钟昼夜节律和免疫基因表达的影响，并确定光照制度如何改变鳟鱼对感染的易感性。据预测，延长和/或恒定的光周期会增加对疾病的易感性。此外，我将量化Gyrodactylus基因表达的昼夜节律，并将这些发现与寄生虫活性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日常变化，驱动了寄生虫生存和宿主行为的昼夜节律。最后，我将确定鳟鱼皮肤的微生物组（细菌群落）是否表现出昼夜节律性，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易感性。据预测，由于抗生素的使用，有益皮肤微生物的变异减少，将增加对寄生虫的易感性。利用最佳昼夜节律的力量可以改善健康并减少水产养殖中抗菌素的使用。总而言之，这项研究的结果将为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相互作用的理解。

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.