Crosstalk between apoptosis and autophagy

Cells possess distinct pathways that promote their survival or death. Communication between the cell survival pathway of autophagy and the cell death pathway of apoptosis is crucial for determining the best outcome for the cell, and ultimately its fate. Our research identifies the molecular factors that are responsible for this crosstalk.

This can be achieved in a number of the ways. The first is to use an in vivo approach to analyse transgenic mice in which the autophagy regulator known as Beclin has been engineered to either disrupt or enhance its regulation by key components (i.e. proteins) of the apoptosis pathways. This will provide the first physiological readout to determine how important these interactions are in crosstalk between the pathways.

The second approach is to use either the new gene editing CRISPR/Cas9 technology or mass spectrometric/proteomics approaches (or both) to undertake screens to identify factors that can inhibit the cell death that occurs as a consequence of disarming the autophagy pathway through deletion of Beclin.

Results from this work will significantly advance our understanding of how the interplay between cell death and cell survival is regulated, which is still poorly understood despite its considerable biological importance. This crosstalk is fundamental to not only physiology but significantly contributes to the onset of diseases such as cancer, and hence impacts on treatment strategies.