Molecular mechanisms and functions of noncanonical autophagy

Autophagy (self-eating) is an evolutionarily conserved catabolic process in cells.

Emerging evidence shows the existence of autophagy-independent functions of the autophagy machinery (noncanonical autophagy, NCA), which play an important role in immune regulation and inflammation, host-pathogen interaction, neuronal signaling and anti-cancer immunity. However, molecular mechanisms and functions of NCA processes remain largely unclear.

As these cellular processes are highly dynamic, of importance to understand these processes is to control protein function with temporal precision in the cell and to reconstitute the system with chemically defined components. Herein, I propose to use chemical genetic methods to address these problems.

I have identified novel natural product (cinchona alkaloids)-inspired compounds that induce the NCA pathway instead of canonical autophagy in cells.

I aim to elucidate fundamental molecular mechanisms of noncanonical processes of autophagy proteins and their new functions in autophagy-independent pathways.

The compounds developed in this project could serve as important research tools but also facilitate the development of new therapeutics.