鱼类的耐寒能力取决于其对低温环境的适应，而对低温刺激的感应，并将低温信号传递到细胞内的过程，是鱼类低温适应的关键环节。我们的前期研究发现，低温暴露后斑马鱼体内的钙离子信号通路被快速激活，而且阻断钙离子信号通路能完全抑制低温适应，说明钙离子信号系统在鱼类低温适应中起着重要作用，但其作用机制尚不清楚。本项目综合应用小分子药物，蛋白质组和转录组学技术，以及基因敲除和遗传筛选等方法，系统研究钙离子信号通路调控鱼类低温适应的分子机制。主要内容包括：1）应用特异性的抑制剂和激活剂研究钙离子信号系统中关键节点的功能；2）组学研究解析钙离子信号系统中关键激酶的作用机理；3）研制基因敲除斑马鱼模型，研究经典PKC家族成员调控鱼类低温适应的作用机制；4）开展遗传筛选鉴定调控鱼类低温相关钙离子信号通路的关键因子。本项目的获准与实施，将深入揭示钙离子信号系统调控鱼类低温适应的分子机理，为鱼类抗寒育种提供理论依据。

The resistance of fish to cold stress is determined by the acclimation of fish body to low temperature environments. The sensation of cold stress and subsequent transduction of cold signals into cells are the critical events during the cold acclimation process of fish. Our previous studies using zebrafish larvae revealed that calcium signaling pathway could be rapidly activated upon cold exposure and inhibition of calcium signaling completely abolished the cold acclimation effect of zebrafish. These results indicate that calcium signaling system plays important roles in the cold acclimation of fish, but the underlying mechanisms remain to be resolved. This project aims to systematically investigate the molecular mechanisms of calcium signaling system in the regulation of fish cold acclimation by using small molecular drugs, proteomic and transcriptomic technologies, gene knockout and genetic screen methodologies. Main contents include: 1) characterize the function of the components in calcium signaling system by using specific inhibitors and activators; 2) explore the functional mechanisms of the key protein kinases; 3) study the functional mechanisms of the conventional PKC members by developing gene knockout zebrafish lines; 4) unbiasly identify regulators of the cold stress-induced calcium signal by genetic screens. The approval and implementation of this project would uncover the molecular mechanisms underlying the function of calcium signaling system in regulating cold acclimation of fish and provide theory foundations for the breeding of cold-resistant aquaculture fish strains.