Tooze lab Molecular Cell Biology of Autophagy Laboratory
: Areas of interest
Introduction
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.
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 increases and is 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.
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.
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.
