Clocks and Non-Visual Light Detection In Extreme Environments

该项目的研究主题是：疾病的基本机制由于在24小时的一天中发育，所有动物，可能除了在黑暗中发育的动物外，都拥有细胞自主的昼夜节律钟，并显示出有节奏的日常行为。生物钟由黎明和黄昏的阳光设定，并调节过多的细胞，生理和行为过程。扰乱生物钟与许多常见的疾病密切相关，例如糖尿病和癌症风险增加，特别是在那些长时间轮班工作的人中。斑马鱼是时间生物学中公认的模式生物，被广泛用于发育和细胞生物学的研究。它已经被开发为研究细胞周期的昼夜节律控制、光依赖生物学和光诱导的DNA修复机制的极好模型。在我的博士学位期间，我想继续探索光输入途径以及随后的昼夜节律和非昼夜节律细胞过程，使用CRISPR/Cas9敲除斑马鱼中的几个光色素（视蛋白）基因。我希望确定非可见光检测对细胞生物学基本方面的影响。我还将使用其他鱼类，如墨西哥盲洞穴鱼（Astyanax mexicanus）和深海鱼类的Sternoptychinae家庭，已经适应了黑暗的环境。如果光和昼夜节律调节对于维持地球上大多数生命的正常细胞调节和组织功能至关重要，那么像墨西哥盲穴鱼这样的某些动物在没有功能性时钟的情况下如何生存和繁荣？通过研究这些在黑暗中进化和发育的不寻常的动物，我的目标是“阐明”细胞和组织如何适应非节奏环境。这些研究的结果将有助于理解我们自己的生物钟和光反应是如何在人类中被打乱的，因为人们开始生活在一个节奏越来越少的现代世界中。

Project comes under the research theme: Fundamental mechanisms of diseaseAs a result of developing under a 24-hour day, all animals, with the possible exception of animals that have developed in the dark, possess a cell autonomous, circadian clock and show rhythmic, daily behaviour. The circadian clock is set by sunlight at dawn and dusk, and regulates a plethora of cellular, physiological and behavioural processes. Disrupting the clock is strongly associated with many common pathologies, such as diabetes and increased cancer risk, especially in those that perform long periods of shift work. Zebrafish is a well-established model organism in chronobiology, and is widely used to study developmental and cell biology. It has already been developed as an excellent model to study circadian control of the cell cycle, light dependent biology and light induced DNA repair mechanisms. In my PhD, I would like to continue to explore light input pathways and subsequent circadian and non-circadian cellular processes using CRISPR/Cas9 to knock out several photo pigment (opsin) genes in zebrafish. I wish to determine the impact of non-visual light detection on fundamental aspects of cell biology. I will also use other fish species, such as Mexican blind cavefish (Astyanax mexicanus) and deep-sea fish of the Sternoptychinae family that have adapted to a dark environment. If light and circadian regulation is essential to maintain normal cellular regulation and tissue function in most life on earth, how can certain animals like the Mexican blind cavefish survive and thrive without a functional clock? By studying these unusual animals, which have evolved and developed in the dark, I aim to 'shed light' on how cells and tissues have adapted to a non-rhythmic environment. The results from these studies will help to understand how our own clocks and light responses are disrupted in humans, as people begin to live in an ever less rhythmic, modern world.