Neil McDonald

Signalling and Structural Biology Laboratory

We study the structural biology underlying the assembly and activation of growth factor signalling complexes. Growth factor signalling deregulation is a hallmark of cancer and is frequently associated with altered catalytic functions of pathway components. These components form molecular complexes that transduce signals across or within the cell membrane and can combine allosteric, catalytic or recruitment mechanisms to propagate growth factor-initiated signals. They also play crucial roles in establishing and maintaining cell polarity.

The laboratory uses structural methods (crystallography, EM and SAXS), biophysical methods (calorimetry and fluorescence polarisation), enzymatic and cell-based assays, to elucidate signalling mechanisms. We exploit our structural data to develop chemical biology programmes to identify small molecular inhibitors of validated cancer targets.

Figure 1

Structural biology and biochemistry of the RET receptor tyrosine kinase. Background shows staining of a medullary thyroid carcinoma driven by oncogenic forms of RET. (Click to view larger image)

Selected publications

Soriano EV, Ivanova ME, Fletcher G, Riou P, Knowles PP, Barnouin K, Purkiss A, Kostelecky B, Saiu P, Linch M, Elbediwy A, Kjær S, O'Reilly N, Snijder AP, Parker PJ, Thompson BJ & McDonald NQ. Barry J. Thompson and Neil Q. McDonald. aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization. Developmental Cell 2016; 38 , 384-398

Goodman KM, Kjær S, Beuron F, Knowles PP, Nawrotek A, Burns EM, Purkiss AG, George R, Santoro M, Morris EP, McDonald NQ. (2014) RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association. Cell Rep. 8(6):1894-904.

Mouilleron S, Wiezlak M, O'Reilly N, Treisman R, McDonald NQ. Structures of the Phactr1 RPEL Domain and RPEL Motif Complexes with G-Actin Reveal the Molecular Basis for Actin Binding Cooperativity. Structure. 2012;. pii: S0969-2126(12)00335-8

Neil McDonald

neil.mcdonald@crick.ac.uk
+44 (0)20 379 61958

  • Qualifications and history
  • 1991 PhD in Crystallography, Birkbeck College, UK
  • 1991-1994 Postdoctoral Fellow (Lucille P. Markey Scholar), Columbia University, USA
  • 1994 Established Structural Biology Lab at the Imperial Cancer Research Fund, UK
  • 1996 Reader (Associate Professor), Birkbeck College, London, UK
  • 1999 Principal Scientist, Imperial Cancer Research Fund, London. (in 2002 the Imperial Cancer Research Fund became London Research Institute, Cancer Research UK)
  • 2006 Professor of Structural Biology, Institute of Structural Molecular Biology, Birkbeck College, London UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK