We investigate how cells take up large volumes of their medium into internal vesicles through macropinocytosis, and how they move towards attractive chemicals through chemotaxis. Both processes are highly conserved and use actin dynamics to shape projections from the plasma membrane. These projections either form a cup to engulf a droplet of medium or a pseudopod (or bleb) to move the cell forward. We have found that macropinocytosis in the amoeba Dictyostelium is regulated by the RasGAP, NF1. NF1 is a common human disease gene and tumour suppressor, but this is the first time it has been linked to macropinocytosis. We find that NF1 is targeted to macropinosomes and are trying to discover how this is achieved. Macropinosomes form around areas of intense Ras and PIP3 signalling in the plasma membrane that most likely act as a template for the characteristic cupped projections of macropinosomes. We seek to understand how this template works and the macropinocytic cups develop and close. The insights gained from amoebae are being extended to a range of human normal and cancerous cell lines. Dictyostelium cells chemotax towards cyclic-AMP and we have shown that this is controlled through a MAP kinase, whose role we are dissecting. Many cells can switch to an alternate mode of movement, based on blebs, when faced with mechanical resistance such as they experience in a tissue. Using a cell ‘squasher’ to impose load on cells, we have analysed the transition to blebbing motility in detail and identified a signalling process that may mediate it. For this work, we use molecular genetics, protein mass-spectroscopy, biochemical assays and advanced microscopy.