Characterisation of lymphocyte function during tissue regeneration and natural ageing

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The completion of this project will help us to understand the effect adaptive immune cells have after a tissue is injured. We are born with cells of our innate immune system but our adaptive immune system develops over time and "learns" and "remembers" pathogens we encounter throughout our lives. The adaptive immune response is vital for fighting off many different infections and is made up of several different types of specialist cells which work together to protect us. Cells of our innate immune system, such as neutrophils and macrophages, fight infections too but are also vital in the response to tissue damage, helping injuries to heal in many different ways. The function of both our innate and adaptive immune system can decline as we get older, potentially affecting how well we can heal after injury. Some animals, such as zebrafish, are able to fully replace cells that were damaged or died as a result of an injury, without forming permanent scars, and innate immune cells like macrophages are vital for allowing this to happen. This suggests that understanding cells of the zebrafish immune system may hold the key to encouraging cells and organs of other animals to repair better or even regenerate. Certain types of adaptive immune cells (lymphocytes) influence these innate immune cells and this can both help and hinder the response to injury. Whether these lymphocytes are helpful or harmful to injury repair depends on several different factors, such as the type of cell being studied, the organ they are in or the type of injury, but we do not fully understand all these complex factors. For a long time it was thought that animals such as zebrafish had a less complex immune system than us and that was a reason why they can regenerate but mammals like us can't. However, we now know that zebrafish have very similar immune cells to us and we have shown that zebrafish lymphocytes also respond to an injury. The more we can learn about how zebrafish immune cells, including lymphocytes, can benefit regeneration the closer we could be to understanding how natural regeneration works and finding ways to encourage our cells to regenerate too. Currently, there have been very few studies into lymphocytes in any animals that can regenerate and so this project aims to address this gap in our knowledge. We will thoroughly map the different lymphocytes that respond to different types of injury in an adult zebrafish, investigate the effect of the loss of these cells on injury repair and regeneration and evaluate what happens to these cells as the fish get older. The completion of this project would provide much more information on how all different types of immune cells work together to facilitate tissue regeneration in zebrafish, helping us to identify better ways to promote injury repair in all animals.