Many signal transduction pathways cells involve enzymes that generate either soluble or membrane-resident second messengers by modifying membrane phospholipids. We are developing a detailed structural understanding of the network of interacting pathways involved in phospholipid signalling. Our current efforts focus on phosphoinositide 3-kinases and their downstream effectors. Due to their frequent mutation in human cancers, a structural understanding of heterodimeric, class I PI3Ks is important for drug development. We are working on the structural biology of all isotypes of class I PI3Ks. Amongst many cellular processes regulated by a class I phosphoinositide 3-kinase recognition is membrane protein sorting into multivesicular bodies (MVB). We are determining the structures of endosomal protein complexes in order to understand how they assemble and fulfil their roles in cargo selection, localisation and inward membrane budding.