Computational Modeling of Cellular Response to Perturbation
Sudin Bhattacharya
Research Investigator, Division of Computational Biology
The Hamner Institutes for Health Sciences
Research Triangle Park, NC
A core set of “signaling motifs” embedded in larger molecular regulatory networks
underlie the response of cells to physiological or environmental perturbation. I
will describe some examples of quantitative modeling of cellular response with
deterministic and stochastic approaches. One example concerns the suppression of
differentiation of B cells in the mammalian immune system to antibody-secreting
plasma cells by the environmental contaminant TCDD. Kinetic modeling of the
transcriptional regulatory motifs governing B cell differentiation predicted
all-or-none physiological switching from the B cell to the plasma cell state and
also binary suppression of this process by TCDD. Both predictions were later
confirmed in the lab. I will also discuss a simple mathematical model to compute
the “epigenetic landscape” underlying cell fate regulation based on the kinetic
interaction parameters of the underlying transcriptional circuit. Finally, I will
describe ongoing work on mapping intracellular “toxicity pathways” based on
transcriptomic and genome-wide transcriptional binding data sets.