Sharon Tooze

Molecular Cell Biology of Autophagy Laboratory

Autophagy is a self-eating process that cells use primarily as a survival response, and which is closely aligned with the machinery that controls cell growth. Autophagy is increased and used for cell survival during periods of nutrient deprivation or stress caused by unfavourable environments. It is also used by cells to maintain the health of their internal organelles thus minimising damage and perturbation of cellular homeostasis.

Alterations in both the basal and amplified survival response modes of autophagy have been shown to be important for the development of disease, in particular cancer and neurodegeneration.

My current and future interests aim to expand our knowledge of the core autophagy proteins and novel effectors and use this information to explore the role of autophagy in human disease.

The short-term goal is to advance the understanding of autophagosome formation at a molecular level using amino-acid starvation to acutely and robustly induce autophagy. The long term goals are to translate these molecular details to understand what role autophagy has in human disease.

Our current work on the core proteins focuses on gaining new knowledge of how these proteins function at a molecular level, in particular through protein-protein interactions, to coordinate the cellular machinery to make an autophagosome. In parallel, we study the downstream effectors of these core proteins and trafficking complexes we have shown are required for autophagosome membrane formation and expansion.

Figure 1

A panel of images from the cryo-CLXM analysis of HEK293 cells expressing mRFP-Atg9 and GFP-LC3. Left, cryo-fluorescence, middle reconstructed tomoX stack, and right, tomogram of the Atg9-compartment (red arrows) adjacent to endosomes (yellow) and GFP-LC3 positive forming phagophores (green arrows) which are seen on ER membranes (blue). White/Black arrows indicate gold particles used for orientation. See Duke et al., 2014 for details. (Click to view larger image)

Selected publications

Dooley HC, Razi M, Polson HEJ, Girardin SE, Wilson MI, Tooze SA (2014) WIPI2 Links LC3-Conjugation with PI3P, Autophagosome Formation and Pathogen Clearance by Recruiting Atg12-5-16L1. Mol Cell. 2014;55(2):238-52

McAlpine, F., Williamson, L.E., Tooze, S.A. and Chan, Y.W. Regulation of nutrient-sensitive autophagy by uncoordinated 51-like kinases 1 and 2. Autophagy, 2013; 9:361-373.

Longatti A, Lamb CA, Razi M, Yoshimura S, Barr FA, Tooze SA. TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive recycling endosomes. J Cell Biol. 2012;197(5):659-75

McKnight NC, Jefferies HB, Alemu EA, Saunders RE, Howell M, Johansen T, Tooze SA. Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. EMBO J. 2012;31(8):1931-46

Orsi A, Razi M, Robinson D, Weston AE, Collinson LM, Dooley H, Tooze, SA. Dynamic interactions of Atg9 with early autophagosome precursors, but not membrane integration, is required for autophagy. Molecular Biology of the Cell. 2012;23(10):1860-73

Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbé S, Clague MJ, Tooze SA. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy. 2010;6:506-522

Webber J, Tooze SA. Coordinated regulation of autophagy through mAtg9 and p38IP by p38α MAPK. EMBO J. 2010;29:27-40

Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domain using an Atg13-independent mechanism. Molecular and Cellular Biology. 2009;29:157-171

Morvan J, Köchl R, Watson R, Collinson LM, Jefferies HB, Tooze SA. In vitro reconstitution of fusion between Immature Autophagosomes and Endosomes. Autophagy. 2009;5:676-689

Razi M, Chan EYW, Tooze SA. Early Endosomes and Endosomal Coatomer are required for Autophagy. Journal of Cell Biology. 2009;185:305-321

Chan EY, Kir S, Tooze SA. siRNA screening of the kinome identifies ULK1 as a multi-domain modulator of autophagy. Journal of Biological Chemistry. 2007;282:25464-25474

Sharon Tooze

sharon.tooze@crick.ac.uk
+44 (0) 20 7269 3122

  • Qualifications and history
  • 1987 PhD, University of Heidelberg, Germany
  • 1990 Research Scientist, European Molecular Biology Laboratory, Germany
  • 1994  Established lab at Imperial Cancer Research Fund, UK (in 2002 the Imperial Cancer Research Fund became Cancer Research UK)
  • 2015 Group Leader, the Francis Crick Institute, London, UK