University of Dundee

How do FAM83 proteins streamline Casein Kinase 1 (CK1) signalling in cells?

The Sapkota lab works on defining the molecular mechanisms that underpin key cellular signal transduction networks, including TGFβ and Wnt pathways. We are interested in understanding how the misregulation of cellular signalling pathways causes human diseases. We collaborate with leading pharmaceutical companies with our exciting findings and innovative tools to explore and expedite drug discovery programmes. The CK1 family of constitutively active protein kinases controls a plethora of cellular processes, including circadian rhythm, cell cycle, response to DNA damage and Wnt signalling. Misregulation of CK1 activity is associated with many human diseases, yet the regulation of CK1 activity, substrate specificity, subcellular localization and turnover are still understood poorly. Recently, our lab has discovered that the FAM83 family of poorly characterized proteins serve as anchors for CK1 isoforms and potentially act as key regulators of CK1 in cells by directing CK1 isoforms to distinct subcellular compartments and substrates. The prospective student will dissect the molecular mechanisms by which FAM83 family members control CK1 biology in cells and human diseases.The project will offer outstanding training opportunities in cutting-edge technologies in cell and molecular biology, protein chemistry, and biochemistry, including CRISPR/Cas9 genome editing, mass-spectrometry, transcriptomics, fluorescence microscopy and our recently engineered Affinity-directed PROtein Missile (AdPROM) system.