<p>While one can surely identify numerous cases of abnormal gene expression in cellular systems, we turn our attention to one particular network related to a crucial decision in cell fate, apoptosis.</p>

In designing a system to target abnormally-absent apoptosis, one can consider two approaches.  It is possible to identify a key anti-apoptotic factor that requires down-regulation or, conversely, to target a pro-apoptotic factor that requires up-regulation.  For the former, one might consider X-linked Inhibitor of Apoptosis (XIAP), which, while not present on the above figure, is responsible for inhibiting caspases (Vucic and Fairbrother, 2007).  Caspase activation in the apoptotic pathway can be considered to be a point of no return, a trigger for the irreversible decision to undergo cellular suicide.  Downregulation of XIAP should thus help initiate apoptosis.  Alternatively, mutations in the gene encoding p53 have been found to exist in 50% of cancers (Toledo and Wahl, 2006).  These mutations occur overwhelmingly in the DNA binding domain of this protein, thus disabling its ability as a transcriptional regulator.  Since the inhibition of apoptosis stems from a defective p53, it might be necessary to introduce a protein into the cell with analogous activity to p53.  Upregulation of this exogenous genetic input would then result in apoptosis.  

While still an ongoing debate, there is increasingly more evidence to suggest that yeast have apoptosis as well (Frohlich et al., 2007).  Despite the fact that apoptosis seems to make most sense in a multicellular context, the organisms nonetheless show signs characteristic of a programmed cell death. In fact, much research about apoptotic pathways from mammals can be conducted in yeast, due to the fact that many of the genes and pathways present in mammals share homology to those found in yeast.  Given this promising range of homology, one might consider first applying the regulatory approach discussed above for mammals in a yeast framework.  A limiter device in yeast could also serve as a useful tool for understanding important nodes in the apoptotic network.