Regulation of primary cilia formation and hedgehog signalling by a PDZ domain protein with function in melanoma growth

The Hedgehog signalling pathway is one of the key developmental pathways essential for cell fate specification, proliferation and tissue patterning. Aberrant activation of the pathway contributes to cancer cell proliferation and survival. The lab has identified GIPC3, a PDZ domain containing protein, and showed that it positively regulates Hedgehog signalling in Hedgehog-responsive fibroblasts and melanoma. In my URECA project we found that GIPC3 is required for ciliogenesis in mouse embryonic fibroblasts. In this project, we sought to understand the molecular mechanism of how GIPC3 regulates Hedgehog signalling and ciliogenesis. We confirmed that in another mouse fibroblast cell line derived from NIH3T3, overexpression of GIPC3 alone is sufficient to potentiate the ligand induced Hedgehog pathway response, signifying GIPC3 as a possible therapeutic target. Additionally, through various efforts of mechanistic studies, we have determined that GIPC3’s role in ciliogenesis is likely a universal effect in Hedgehog-responsive fibroblast cells. A series of experiments are in the pipeline to decipher the molecular mechanism of GIPC3 and its role in Hedgehog signalling and ciliogenesis. Data from this project aids in unravelling the function of GIPC3 and contributes towards the quest in developing an effective therapeutic against melanoma and Hedgehog-driven diseases.Bachelor of Science in Biological Science