Primary biliary cirrhosis (PBC) is the most prevalent of adult autoimmune liver diseases, seen in both genders and all ethnicities, but remains without rational treatment. Its immune mediated liver injury is driven by interacting innate, humoral and cellular pathways, on a strong background of genetic and environmental risk. Improved treatment is a priority for patients but is hindered by a) complexity inherent to composite genetic and environmental risks; b) inadequate understanding of molecular pathways linking gene signatures to disease and c) challenges associated with personalising and stratifying treatment. We seek to capture the unique and globally recognised strengths of our autoimmune liver disease research programme in Birmingham, to translate our high impact novel genetic risk associations in PBC, to better understanding of pathogenesis, and thereby develop stratified medicine approaches to effective clinical markers and treatment. We will define and profile a cohort of patients with PBC at a molecular level over time; develop rational targets for treatment by laboratory interrogation of the immunoregulatory pathways identified by our own genetic studies; and over the coming years change treatment perspective by bridging biophenotype to clinical practice, utilising novel biomarkers for monitoring and predicting outcome, as well as facilitating targeted personalised treatments.