We study how cells protect and rejuvenate themselves by assembling on-demand waste disposal units, and how we can exploit and modulate this process to improve human health.
When a cell runs out of nutrients, when organelles stop working or when bacteria or viruses invade the cell, a dedicated structure forms from scratch sequestering the intruder, site of damage or a random portion of cellular material. It destroys its contents and recycles the cellular building blocks within.
The underlying process – known as autophagy – therefore protects the cell, keeps it healthy and equips it with a remarkable flexibility to adapt to its ever-changing environment. But when this process goes wrong, it contributes to human diseases such as cancer, neurodegeneration and infection.
Autophagy is too complex to solely study in the crowded and complex environment of a cell. We have therefore developed a cell-free system to rebuild it in the test tube to understand when, where and how each of the autophagy factors contributes to the process.
This system can be manipulated easily, allowing us to dissect and visualise the different steps by a combination of biochemical, biophysical and structural biology approaches to gain unprecedentedly detailed molecular insights into the mechanism. We also validate and complement this work by investigating autophagy in cells using genetic, proteomics and imaging approaches to identify novel regulators and to understand the process in its entirety.
Our long-term aim is to substantially advance our understanding of autophagy and thereby aid the development of new diagnostic and therapeutic tools.