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Mariann Bienz is Senior Staff Scientist at the MRC Laboratory of Molecular Biology. She has studied the mechanisms of cellular signalling pathways during normal development and their relevance for cancer. Her early work was on the transcription of developmental control genes and their regulation according to the position of cells within an embryo. She was the first to exploit the Drosophila midgut as a model experimental system: she discovered that the endodermal cells are patterned by signals from the overlying mesodermal cells, and that these signals also regulate the gene Ultrabithorax which initiates this inductive cascade. Her systematic analysis has yielded a molecular description of this entire pathway, revealing how extracellular signals are translated into specific switches in gene activity, and cell differentiation. Her work revealed that the Wnt signalling pathway plays a critical role during this process and this has been a major focus of her work. Using a Wnt-responsive midgut enhancer from the Ultrabithorax gene she identified the transcription factors that read out and interpret the different Wnt signalling levels. She thus discovered a central role of the TCF transcription factor in integrating Wnt and other signalling inputs. More recently, she combined Drosophila genetics and mammalian cell biology to unravel the mechanism of Wnt signal transduction. Her main focus was the Adenomatous polyposis coli tumour suppressor whose activity had been linked to the Wnt pathway. She uncovered a dual function of this protein in down-regulating Wnt signalling and in maintaining cellular adhesion, based on its ability to shuttle between nucleus, cytoplasm and cell membrane. So this is where the story comes back to human disease. This observation provided an explanation for the potent tumour suppressor activity of this protein in the human intestine. She also discovered a new nuclear component of the Wnt signalling pathway with a function in colorectal cancer cells, thus providing a potential therapeutic target.