Targeting RBCK1 disease mechanisms

The research fellow will develop the experimental plan under the supervision of the tutor and a senior postdoc. Starting with iPSC lines previously derived from patients’ fibroblasts, the researcher will be responsible for differentiating them into 2D musculoskeletal stem cells and for generating 3D organoid models. To characterise the inflammatory profile, molecular genetics and transcriptomics experiments will be conducted under basal conditions and following LPS-induced stress. For mitochondrial dysfunction, the system will be stressed instead with galactose and similarly analysed. Once a reliable readout has been identified from the stem cell characterisation experiments, a panel of FDA/EMA-approved drugs will be tested to identify an effective therapy. In addition, the researcher will conduct experiments to develop gene therapy using genetic engineering techniques such as CRISPR/Cas9.