Bioinformatics and Functional Genomics
The human apoptosis network adapted from that in the Kegg database (hsa04210). There are 47 genes in the figure and an additional node which we label the output node. The 47 genes may be categorized as: input genes (dashed circles); membrane genes; death genes (purple); life genes (35,36,37,39); and finally the remaining genes in the network. The output, or "death" node (48) is added to represent the cumulative effect of many genes implicated in the onset of the cell death machinery. Solid arrows denote promotion, while dashed lines indicate inhibition. The long dashed line between CASP3 and CASP8 represent feedback in the apoptosome and leads to bistability in cases where co-operative non-linearity exists. We are developing models for signaling in apoptosis. Of particular interest is the selectivity problem, where we optimize intervention strategies to kill one member of a diverse population while leaving the other members of the population as unaffected as possible. Experiments involving optimization of drug combinations to kill selected cells while leaving others alive are under way at the Burnham Institute.
Research Team: Phillip Duxbury (Physics), Carlo Piermarocchi (Physics), and Giovanni Paternostro (Burnham Institute)