Cilia: a new therapeutic target for type 1 diabetes?

Type 1 diabetes (T1D) is a chronic autoimmune disease where the immune system destroys insulin-producing β-cells in pancreatic islets, leading to lifelong insulin dependence and increased risk of multi-organ complications. Despite advances in care, the triggers of β-cell destruction remain poorly understood, limiting efforts to develop preventative therapies. This proposal investigates a virtually unexplored aspect of islet biology: the role of cilia, specialised signalling structures found on islet cells, in regulating cell communication and controlling vulnerability to immune attack. Using advanced imaging and genetic tools, I will: (i) map cilia-associated genes and proteins across islet cell types to identify disrupted signalling pathways; (ii) determine how cilia dysfunction alters intercellular communication, potentially exposing β-cells to immune destruction; (iii) compare cilia structure and gene expression in healthy, at-risk, and diabetic human and mouse islets; and (iv) assess how cilia loss affects islet composition, hormone secretion, and immune infiltration in cilia-deficient mouse models. This work proposes a shift in understanding T1D, suggesting that cilia-mediated signalling is essential for maintaining islet homeostasis and that its disruption contributes to disease. By uncovering how cilia coordinate islet cell interactions, I aim to reveal new immune triggers and identify therapeutic targets to prevent or halt T1D progression.