Roger Williams

Structural studies of phospholipid signalling
Personal group site

Most receptor-mediated signal transduction pathways in mammalian cells involve enzymes that generate either soluble or membrane-resident second messengers by modifying phospholipids present in cell membranes. These enzymes are activated in response to a variety of cellular signals such as hormones, cytokines and neurotransmitters.

We are trying to develop 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 and their roles in the immune systems, a structural understanding of class I PI3Ks is important for drug development.

Amongst many cellular processes regulated by specific phospholipid recognition are membrane protein sorting into multivesicular bodies (MVB) and autophagy, which are dependent on 3-phosphoinositides derived from class III PI3Ks.

We are determining the structures of endosomal and autophagosomal protein complexes.

In addition to X-ray crystallography, we are using electron microscopy, protein engineering, biophysical methods and in vivo assays to characterise these regulatory interactions.

Selected Papers

Group Members

  • Olga Perisic
  • Yohei Ohashi
  • Alex Berndt
  • Domagoj Baretic
  • Glenn Masson
  • Apostolos Apostolakis
  • Ksenia Rostislavleva
  • Alison Inglis
  • Lauren McGinney
  • Madhanagopal Anandapadamanaban