Cold adaptation of cellular sgnalling cascades: The role of the master regulator of oxygen homeostasis HIF-1 (Hypocia inducible factor) in Antarctic fishes

南极鱼已经进化成一种高度适应寒冷的表型，包括对O2运输系统的各种适应。据推测，冷适应还涉及由转录因子HIF-1介导的O2依赖性基因表达的修饰。缺氧诱导亚基HIF-1的测序？从一个温带和四个冷适应的南极鱼类中检测到与哺乳动物或其他非极地鱼类相比，这可能反映了转录因子的冷适应，并表明蛋白质的功能和/在本研究中，我们将探讨HIF-1在寒冷环境中的生理学意义和作用，以及HIF-1在寒冷环境中的作用机制。本研究将以南极适应性鱼类为研究对象，探讨南极适应性鱼类是否存在缺氧诱导因子，不同的缺氧条件是否能诱导缺氧诱导因子，以及缺氧诱导因子反应可能介导何种生理效应。在第二个目标中，将研究调节冷适应鱼类中HIF反应的分子机制。本部分的目的是阐明这种机制的进化变化相比，温带鱼类，也比较吸热动物（哺乳动物模式生物），共同提出的研究将扩大我们的知识，这一重要的生理调节，主调节器的氧稳态和拓宽我们的一般理解冷适应的重要调控信号cascade。

Antarctic fish have evolved into a highly cold-adapted phenotype, including a variety of adaptations of the O2-transport system. It is hypothesised that cold adaptation also involves modification of O2-dependent gene expression mediated by the transcription factor HIF-1. Sequencing of the hypoxia-inducible subunit HIF-1¿ from one temperate and four cold-adapted Antarctic fishes have detected remarkable differences in the deduced peptide sequences compared with mammals or other non-polar fishes, which might reflect cold adaptation of the transcription factor and suggest that the protein function and/or the regulatory mechanism has undergone a different evolution in polar fishes than in mammals.In the proposed project the physiological importance and assignment of HIF-1 in cold-adapted Antarctic fishes will be studied to know whether there is HIF in these fishes, whether HIF can be induced by different hypoxia conditions and what kind of physiological effects might be mediated by the HIF response. In the second objective the molecular mechanisms regulating the HIF response in cold-adapted fish will be investigated. This part aims to clarify the evolutionary change of this mechanism in comparison to temperate fish and also in comparison to endothermal animals (mammalian model organisms).Together, the proposed studies will extend our knowledge on this important physiological modulator, the master regulator of oxygen homeostasis and broaden our general understanding of cold adaptation of important regulatory signallingcascades.