Dr Roger Williams

MRC Laboratory of Molecular Biology

NHS or other affiliations
Laboratory of Molecular Biology

Position: Group leader
Personal home page: http://www.mrc-lmb.cam.ac.uk/rlw/text/rlw_homepage/Home.html

PubMed journal articles - click here

Dr Roger Williams is pleased to consider applications from prospective PhD students.

Research description

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.

Research Programme or Virtual Institute
Fundamental Biology of Cancer

Key publications

Miled, N., Yan, Y., Hon, W.C., Perisic, O., Zvelebil, M., Inbar, Y. , Schneidman-Duhovny, D., Wolfson, H.J., Backer,J.M. Williams, R.L. (2007) Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science 317:239-242. Knight, Z.A.,Gonzalez, B., Feldman, M.E., Zunder, E.R., Goldenberg,D.D., Williams, O., Loewith, R., Stokoe, D., Balla, A., Toth, B., Balla, T., Weiss,W.A., Williams, R.L., Shokat, K.M. (2006) A pharmacological map of the PI3-K family defines a role for p110a in insulin signaling. Cell 125:733-747. Pacold, M.E., Suire, S., Perisic, O., Lara-Gonzalez, S., Davis, C.T., Walker, E.H., Hawkins, P.T., Stephens, L., Eccleston, J.F. & Williams, R.L. (2000) Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase ?. Cell 103, 931-943.