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The Virtual Embryo Project (v-Embryo™):
A computational framework for developmental toxicity

Science Challenges

Developmental systems biology

The ‘e-science’ enabled by v-Embryo™ aligns with recommendations from the National Research Council’s recent (2007) report on "Toxicity Testing in the 21st Century: a vision and strategy" (http://www.nap.edu/catalog/11970.html), transforming traditional toxicity testing into one focused on detailed mode of action (MOA) and dose response information for human health risk assessment. That said, engineering the in silico solutions to predict MOA in development will be a problem more challenging than what has been encountered for physical phenomena. This is partly due to the existence of many interrelated molecular interactions (some of which are yet undiscovered) and the additional complication that teratogenesis is a threshold phenomenon.

Understanding teratogenesis at a systems level requires thinking about how toxicity pathways are integrated with the genomic control of conserved cell signaling pathways. This requires substantial investment in bioinformatics and applied mathematics in order to interpret biological responses from the myriad of interrelated data and associative relationships covering the exposure-disease continuum, and presumes reasonable knowledge of biological networks under normal conditions and the behavior of cellular networks during chemical insult and in different model systems.

Hypothesis

v-Embryo™ is a platform to test the hypothesis that critical effects of environmental agents on developmental toxicity pathways may be encoded as computer simulations of morphogenetic processes that draw from knowledge regarding the flow of molecular regulatory information in rudimentary tissues, the cell-autonomous responses to genetic (programmed) and environmental (induced) signals, and the emergent morphogenetic properties associated with collective cellular behavior in any given system.


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