We are interested in membrane trafficking controlled by the phosphoinositide lipids (PIs). PIs are constituents of endomembranes that are dynamically phosphorylated and dephosphorylated. These modifications can generate seven structurally and biochemically distinct lipid species that essentially contain a code specifying the recruitment of effector proteins. This ‘code’ defines regions within membranes that are particularly important in the sorting of membrane-bound cargoes into pathways leading to degradation and recycling.
As molecules that contain trafficking information the PIs are key determinants of membrane identity and, together with proteins such as the Rab GTPases, they control important membrane transport pathways that maintain the basic membrane organisation of the cell. Defects in PI metabolism can have dramatic effects on cell physiology, which accounts for our diverse interest in human diseases.

Achievements
•    Molecular identification of the type II A and B PI 4-kinases.
•    Showed that PI4K2A regulates EGFR degradation.
•    Deletion of PI4K2A in mice leads to late-onset neurodegeneration (with P. Simons).
•    Cholesterol regulates PI4K2A mobility in TGN and endosomal membranes.
•    Demonstration that PI4K2A and PI4K2B synthesise PI4P in metabolically separate membrane domains.
•    PI4K2B regulates the formation of invasive structures.
•    Loss of PI4K2B function is a risk factor for human cancers.