Clocks and Non-Visual Light Detection In Extreme Environments

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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.