Targeted Activation of Programmed Cell Death Pathways by Optogenetics.

Regulated cell death is an important biological process by which an organism removes unwanted, malignant, or infected cells. Although it has become clear that different forms of regulated cell death exist, it remains difficult to compare their consequences at the cellular and tissue level as they are induced by different stimuli and proceed with different kinetics. Moreover, it was so far difficult to target and induce cell death in selected cells within cell populations or complex tissues without affecting its neighbors. To overcome these obstacles researchers developed novel synthetic biology tools that use chemical or optogenetic approaches to specifically induce PCD in selected cells. Here, we describe a protocol for optogenetic activation of three major types of regulated cell death: apoptosis, necroptosis, and pyroptosis, using light-induced forced oligomerization of their major effector proteins (caspases or kinases).