“The programmed cell death response is very discrete, and we were interested in answering the question of what makes death stop,” says Dinesh-Kumar. To that end, the team used RNAi to identify genes involved in disease resistance and the programmed cell death response. They struck death paydirt when they silenced BECLIN1, a gene that has been implicated in autophagy based on its abilities to rescue autophagy-defective yeast and to prevent premature senescence in plants.
Whether the plant was attacked by viral, bacterial, or fungal pathogens, BECLIN1 and other autophagy genes limited pathogen-induced cell death to the infection site and also repressed viral replication. These findings contrast with the situation in mammalian cells, where autophagy genes are required for initiating programmed cell death when apoptotic machinery is compromised. Autophagy may promote cell survival by controlling the production of the pro-death signal, preventing the movement of the signal into uninfected cells, or protecting cells against cellular damage caused in defense against pathogenic invasion.
The group also discovered that the spreading pro-death signal does not arise from the virus itself. Sites of virus infection within leaves did not expand despite extensive cellular death throughout the plant, and plants infected with just the viral protein that elicits the programmed cell death response still showed widespread cell execution despite the viral protein's inability to move. The big mystery, and a new focus for Dinesh-Kumar's research, therefore centers on identifying this mobile pro-death signal and its origin.