Feeding is basic to all cells and movement to many.  Free-living amoebae can feed by taking up droplets of nutrient-rich medium into internal vesicles called macropinosomes.  This medium is processed through an internal digestive system and soluble nutrients extracted.  Macropinocytic uptake is evolutionarily conserved and adapted by immune cells to sample for foreign antigens in their environment and can be hijacked by pathogens as a way of entering cells.  Most surprisingly it appears that cancer cells can also feed in this way.

As macropinocytosis is relatively poorly understood, we are seeking a basic understanding of it using both Dictyostelium amoebae and mammalian cells.  Macropinosomes are formed by the closure of cups driven out from the plasma membrane by a ring of polymerizing actin. Macropinocytic cups organize around patches of intense Ras and PIP3 signalling, whose size is controlled by the tumour suppressor, NF1 (neurofibromatosis-1), which functions to inactivate Ras.  Macropinocytic cups are self-organizing over a scale of several microns and we have proposed a ‘template hypothesis’ for their formation, based on their recruitment of nucleators of actin polymerization to the periphery of the Ras/PIP3 patch, but not to its centre.  We are now seeking to identify further components of these patches, how they are organized in space and how they are regulated by NF1.

Cells move by extending their leading edge using either pseudopods or blebs, and they can be guided to their destinations by many different environmental signals, including gradients of attractive chemicals.  Pseudopods and blebs seem to be advantageous for moving in different environments and we are trying to understand how cells choose between them and how they can be orientated to the front of the cell by chemotactic gradients.

We also have an earlier interest in genomics, polyketide signalling and sex determination in Dictyostelium.