ESR5

Molecular mechanisms balancing the output of ciliary TGFβ/BMP signalling


TGFβ/BMP signalling controls a complex network of spatiotemporal signalling pathways, which when dysregulated are major causes of developmental disorders and cancer. We discovered that this signalling is coordinated by primary cilia and that activation of downstream signalling pathways is coupled to intraciliary trafficking as well as internalization and recycling of receptors at the ciliary base. However, the mechanisms underlying these trafficking events are largely unknown. ESR5 will decipher the molecular mechanisms by which primary cilia balance the output of diverse TGFβ/BMP pathways to control cellular and developmental processes using high resolution fluorescence microscopy and live cell imaging of cultures of wild type and CRISPR/Cas9-generated knockout cells and by designing structure-based IFT, BBSome and RAB protein mutants that impede ciliary trafficking, internalization and post-translational modification of TGFβ/BMP receptors and associated downstream signalling proteins without inducing ciliary loss. Mutant protein designs and proteomics/data analyses will be done in collaboration with P6-AU/P3-IMAGINE and P8-EKUT/P11-CellNetworks, respectively. In collaboration with ESR12 and P10-ZeClinics, ESR5 will translate how ciliary trafficking events control developmental processes guided by TGFβ/BMP signalling in zebrafish

Partner: University of Copenhagen, Denmark

Supervisor: prof dr S.T. Christensen