Mismatch repair (MMR) proteins ensure that mistakes during DNA replication are corrected. We use budding yeast and human siRNA screens to identify new MMR components that may predispose to Lynch Syndrome- a hereditary cancer predisposition syndrome also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Our goals are to understand how mutagensis is determined in cells and tumours and to identify synthetic sick/lethal (SSL) interactions that can be used to target MMR-defective tumours. To underpin our discovery science, we collaborate with epidemiologists to carry out systematic reviews and meta-analyses to test whether established hypotheses for MMR-mediated tumourigenesis are supported by evidence from the clinic. The discovery science is the foundation for strong translational links via collaborations with Dr. Francis Pearl (joint PhD student) and, more widely, the Drug Discovery Group with the Sussex.