Yang Group – starting May 2025 Inter-organ dynamics in physiology and disease Opportunity for LSI PHD studentship – starting in September 2025 or January 2026 PhD Studentship applications will open on 1st April (link will be here from 1st April), and the deadline will be 9th June 2025. For any information about the project, please contact the lead supervisor, Dr Yu Hsuan Carol Yang: Y.C.Yang@exeter.ac.uk Title of Project: Investigating galanin regulation of pancreatic islet hormone secretion in live zebrafish Supervisory Team: Dr Yu Hsuan Carol Yang (CBS/LSI), Dr Kyle Wedgwood (Maths/LSI), Prof Steffen Scholpp (Bio/LSI) Project details The role of neurons in all aspects of pancreas biology remains underexplored. The release of hormones from the different cell types that make up a pancreatic islet (including insulin from beta cells and glucagon from alpha cells) is tightly coordinated to achieve glucose homeostasis. We hypothesise that neural signalling is critical for tightly regulating the coordination of islet cell activity. Tools required to precisely control pancreatic nerves and to monitor the effects in islets of living animals are difficult to implement in mammalian models. Therefore, we turn to the miniature and translucent zebrafish model where studies are translatable to humans given the high conservation of organs and physiology. We have established assays necessary for studying neural-pancreas interplay in live zebrafish (Yang et al. 2018 and Yang et al. 2022). These tools will be used to target galanin producing neurons to address the following aims: Aim 1: Does hyper-activating pancreatic galanin fibres impact islet physiology? Our studies show projections of galanin nerves into the zebrafish islet from a sub-set of peri-islet neurons. For this aim, we will dissect how these galanin neurons modulate islet function with inducible optogenetic tools. The student will learn in vivo confocal imaging to evaluate islet phenotypes with our toolbox of fluorescent reporters and biosensors (including cell number, organ architecture, cell health status, and cell activity/connectivity) and link them to changes in glucose levels upon hyper-activation of galanin signalling. Additionally, we will conduct computational modelling of the cellular connectivity between the different islet cells upon neural regulation. Aim 2: Does losing galanin signalling impact islet physiology? Loss-of-function studies will be used to address whether galanin signalling is necessary for maintaining islet physiology. The student will analyse islet physiology in galanin mutants and upon targeted neuron ablation to support our preliminary observation of defective islet function. Given that galanin receptors are expressed in all islet cell types, the student will generate transgenic lines to optogenetically rescue galanin signalling in specific islet cells with light-sensitive chimeric galanin receptors. This will allow us to determine if cell-type-specific rescue of galanin signalling could reverse the knockout phenotypes. The student will work closely with a cross-faculty interdisciplinary supervisory team providing complementary expertise to guide the student’s project and career progression. The student will develop well-rounded skills: including molecular biology techniques, in vivo imaging, data analysis, computational modelling, and written/oral communication. Following training, the student will be driving the project and have opportunities to present their findings in scientific meetings.