Apoptosis, or programmed cell death, is an important process in the prevention of cancer. The Bcl-2 family proteins are the critical regulators of apoptosis, and consist of both pro-survival and pro-apoptotic proteins. It is the balance between these two sub-groups that determines a cell’s fate. Bfl-1, and its murine homologue A1, are members of the pro-survival sub-group and are relatively under-studied. Bfl-1 and A1 share 72% amino acid sequence homology, have a similar structure and are both mainly expressed in the haematopoetic system. Overexpression of Bfl-1 has been noted in a number of types of cancer, especially in leukaemia and lymphoma. Furthermore, this overexpression is often associated with chemotherapy resistant or metastatic tumours, suggesting a role for Bfl-1 in aggressive disease. Whilst humans only have one copy of the Bfl-1 gene, there are three functional isoforms of A1 in mice (A1-a, A1-b and A1-d) as well as a pseudogene (A1-d) that have arisen from a quadruplication of the gene locus. Knockout of a single A1 gene in mice (A1-a) shows no overt phenotype, suggesting potential redundancy between the isoforms and/or compartment-specific roles for them. A complete knockout has until recently been considered impossible because of the close proximity of the isoforms and other functional genes that intersperse each copy. Our lab has successfully developed a novel system to generate a conditional A1 knockout mouse model, and I intend to use this model as a tool to study the effect of A1 deletion on tumourigenesis and sustained tumour growth. In addition to this I am currently utilising CRISPR/Cas9 technology to explore the role of Bfl-1 deletion in human tumour cell lines in vitro, with a focus on leukaemia, lymphoma and melanoma.