Professor David Barford FRS
Academic Title: Professor of Molecular Biology
Tel: 0207 153 5420/5443
Location: Chester Beatty Laboratories, London
Our research is aimed at elucidating the molecular mechanisms of control for key cell signalling pathways, and the cell cycle, by use of X-ray crystallographic and single particle electron microscopic techniques. The focus has been on pathways and systems that are regulated in response to post-translational modifications and small GTPases and that are relevant to cancer.
This information will provide insights into complex regulatory systems, in terms of control and specificity, and will inform structure-based drug design. Current work is focussed on the anaphase promoting complex (APC/C), enzymes that post-translationally modify the RAS CAAX motif (the membrane proteins RCE1 and ICMT) and guanine nucleotide exchange factors of the DOCK super-family.
Our approach is to understand, at a molecular level, the proteins and protein-nucleic acid complexes that regulate cell processes, with a particular emphasis on elucidating mechanisms that provide specificity in these pathways. Insights into these systems may provide a framework for rational drug design and the development of specific and potent inhibitors that may be effective for the treatment of cancer.
Professor Barford studied Biochemistry at the University of Bristol and undertook his DPhil research at the Laboratory of Molecular Biophysics, University of Oxford in Louise Johnson’s group where he elucidated the structural basis for control of glycogen phosphorylase by protein phosphorylation. He then spent one year in the groups of Philip Cohen and Tricia Cohen at the Medical Research Council (MRC) Protein Phosphorylation Unit, University of Dundee before moving to Cold Spring Harbor Laboratory (CSHL), New York in 1991 as a Cold Spring Harbor Laboratory Fellow. At Dundee and CSHL he initiated his research on protein phosphatases.
In 1994, Professor Barford returned to the University of Oxford as a University Lecturer and was appointed as Professor of Molecular Biology and Co-chair of the Section of Structural Biology at The Institute of Cancer Research in 1999. Here he has focussed his research on proteins regulating signal transduction pathways and the cell cycle.
Professor Barford was elected a Fellow of the Royal Society in 2006, a Fellow of the Academy of Medical Sciences in 2003 and European Molecular Biology Organisation (EMBO) Member in 2003 and was awarded the Colworth Medal of the Biochemical Society in 1998.
Anaphase Promoting Complex (APC/C)
Regulated cell cycle progression is dependent upon controlled ubiquitin dependent proteolysis, mediated by the SCF and the anaphase promoting complex or cyclosome (APC/C), coupled to reversible protein phosphorylation.
DOCK guanine nucleotide exchange factors (GEFs)
DOCK proteins have been implicated in the activation of Rac and Cdc42 in cell migration, morphogenesis and phagocytosis, and as important components of tumour cell movement and invasion.