We are working towards developing phenotypic assays to facilitate molecular and cellular characterisation of OI phenotype using iPSC cell lines. We hypothesise that access to disease-relevant cells with patient-specific variants will provide the most representative models of OI, thus allowing us to set up reliable assays for therapeutic discovery. We are deriving iPSCs from our existing banks of OI patients’ fibroblasts and differentiating these into osteoblasts. We plan to set up a phenotypic assay as a proof-of-principle for future high-throughput drug discovery efforts and in-depth mechanistic studies. 

Through deep phenotyping of rare bone disorders like Osteogenesis Imperfecta, we are also establishing adjuvant findings to aid in the diagnosis of rare bone disorders. The image demonstrates an example of an electron microscopy image from patients with OI with collagen flowers caused by an amalgamation of abnormal collagen fibrils seen in type 1 collagen defects commonly associated with OI.

Through the use of patient-derived cell lines, we are at the forefront of improving understanding of the molecular defects that underpin OI, which is predominantly caused due to a defect in the production, processing or secretion of type 1 collagen, and other rare bone disorders. Leading on from this, we want to establish ways to correct the molecular defect in OI and work towards personalised gene therapies for OI and other rare genetic disorders.

Similarly, our work on rare neurodevelopmental disorders such as HNRNP-NDD are focused on developing gene-directed therapies to reverse the phenotype and make the lives of children and families living with this devastating condition better.