Neil McDonald

Neil completed his doctoral training with Professor Tom Blundell at Birkbeck College where he determined structures of the ß-nerve growth factor (NGF) cystine knot and the multi-protein 7S NGF complex. He also uncovered the first evidence of a ligand-induced allosteric changes within the EGFR. He was then awarded a Lucille P. Markey Scholarship for his postdoctoral training to move to the laboratory of Professor Wayne A. Hendrickson in the Department of Biochemistry and Molecular Biophysics, Columbia University, New York. While there he studied the ciliary neurotrophic factor (CNTF) and its receptors and applied multi-wavelength anomalous diffraction (MAD) methods to determine the structure of CNTF, a potential biotherapeutic produced by Regeneron Pharmaceuticals.

Neil was then recruited back to London in 1994 as a Group Leader in order to establish a Structural Biology Laboratory at the ICRF. ICRF became the Cancer Research UK (CR-UK) London Research Institute and is now part of the Francis Crick Institute. Neil also has held a chair at Birkbeck College as Professor of Structural Biology since 2006.

His research interests lie in the molecular mechanisms underpinning growth factor signalling at the cell membrane. His group has uncovered molecular mechanisms controlling protein kinase and protein phosphatase activation in both physiological and disease settings. More recently his group have explored; (1) the architecture and regulation of many types of membrane-linked proteins and enzymes (2) the molecular function of the RPEL motif, a multi-valent G-actin-binding signature that couples the nuclear accumulation of transcription factors, phosphatases and RhoGAPs to signal-regulated changes in cellular G-actin concentration and (3) structure determination of several opportunistic oncology targets.

His current interests are the assembly and control of neuronal survival and polarity networks. Both are kinase-driven networks with distinctive architectures and each plays critically important and complex roles in human physiology and diseases. A fundamental question linking the laboratory’s research is how the molecular function of key protein kinases within these networks encode instructions that ultimately control cellular behaviours. In parallel to this discovery-based research, the group has also contributed to several CR-UK and Wellcome-funded drug discovery programs, including one that has delivered a first-in-class, pre-clinical candidate against a known cancer target.