Role of CDK9 in zebrafish heart repair and regeneration following resolution of inflammation

The zebrafish larva is an important model organism for investigation of complex in vivo physiological and pathological processes, specifically human disease. In particular tissue regeneration; neonatal mammals have lost the capacity for cardiac regeneration by 7 days of age. In contrast, zebrafish can regenerate all organs and tissues, regardless of age. Newly hatched zebrafish (embryos or larvae) up to 5 days old are NOT considered sentient beings and do NOT feel pain or suffer as defined by veterinary surgeons and the scientific community. As a consequence, they are NOT a protected organism under UK Government and EU legislation. However, zebrafish larvae possess many functional biological responses in order to survive at this early stage of life. In particular, they are capable of defending themselves from infection and protecting themselves from trauma and unwanted tissue damage. These responses, called an inflammatory response, if unchecked or uncontrolled, can lead to acute and chronic inflammatory diseases in animals and humans. In the heart they can lead to scarring and abnormal physiological reponses that in turn can result in heart failure. We hypothesise that when the inflammatory response starts to abate (a process termed inflammation resolution) a new chain of events is set in motion that aids recovery, repair of tissues and, especially in the fish, permits tissue regeneration (a process that occurs in certain mammalian tissues such as the liver but not in many other tissues and organs). In this study we will visualise, quantify and manipulate the inflammatory response especially inflammation resolution in the heart in order to promote tissue repair and regeneration. For this we will investigate the role of key white blood cells, i.e. neutrophils and macrophages cells involved in the inflammatory response and analyse the processes and pathways that our laboratory has shown to be important for inflammation resolution. We strongly believe that using zebrafish larvae to study inflammation resolution will lead to a greater understanding of tissue repair and regeneration that will have a major impact in biological and medical research and contribute to translational medicine.