Our laboratory studies the basic molecular mechanisms of programmed cell death, an evolutionarily conserved process to eliminate cells. Because these pathways normally contribute to the millions of cell deaths that occur per day per individual, defects in cell death underlie the range of human disorders from cancer (insufficient cell death) to neurological diseases (excessive death). We study these processes in the nervous system, in cancer models and during virus infection using mouse models, yeast genetics and biochemical approaches. We have shown that viruses can trigger cells to activate programmed cell death (Levine et al., Nature, 1993), and that both viral and cellular regulators of apoptosis, such as Bcl-2 family proteins and many other factors, can alter the outcome of a virus infection (Lewis et al., Nature Med, 1999). We seek the mechanisms that explain why Sindbis virus induces neuronal cell death in young animals, but fails to activate the death pathway in neurons of adult brains and in mosquitoes that transmit the virus in nature. Interestingly, cell death factors can also be cell survival factors (Cheng et al., Science, 1997), leading us to pursue their important alternative functions, or ‘day-jobs’, such as regulating mitochondrial fission and bioenergetics, synaptic activity in neurons, or nutrient-sensing in yeast. Although it remains controversial as to whether or not unicellular organisms are capable of undergoing programmed cell death, we have new compelling evidence that these pathways are evolutionarily conserved. Therefore, we have launched an effort to apply the genetic and proteomic tools available for yeast to model the death and survival mechanisms that are conserved between yeast and mammals.