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Computational Embryology and Predictive Toxicology
Citation:
Knudsen, T. AND K. Barham. Computational Embryology and Predictive Toxicology. Interagency Modeling and Analysis Group (IMAG) Multiscale Modeling (MSM) Consortium, NA, NC, July 14, 2022. https://doi.org/10.23645/epacomptox.21375654
Impact/Purpose:
Invited presentation to the Multiscale Modeling Consortium (MSM) of the Interagency Modeling and Analysis Group (IMAG) in July 2022 that endeavors to build collaborations for various aspects of integrative biology at multiple scales for computer simulation. This invited webinar will present concepts and progress toward building computer models that can quantitatively predict chemical effects on early emrbyonic development.
Description:
Biologically inspired multicellular systems models that are fully computable (eg, virtual embryo) can be used to titrate critical phenomena during tissue development, homeostasis, and disease; however, in silico reconstitution of a complex, self-organizing morphogenetic system from unidimensional data (embryogeny) remains a challenge. Two examples will be presented from the current VTM portfolio: microglial development and mesoderm gastrulation. (1) Microglial cells are often altered in neurodevelopmental disorders (e.g., RTT, FAS, ASD) and are essential building blocks of microvascular development (angiogenesis) and permeability (barriergenesis). To begin to unravel their complex roles in fetal brain homeostasis, a small working prototype of perineural vascular development was constructed in CompuCell3D.org to translate microglial function into consequences on emergent microvascular patterning. The model can execute predictive biology for modeling neurodevelopmental disorders, including chemical exposures during pregnancy. (2) The embryonic body plan is ‘decoded’ during gastrulation, the hallmark of which is primitive streak formation in the epiblast. Using CompuCell3D.org, we modeled the human epiblast evolving a primitive streak through epithelial-mesenchymal transition of pluripotent stem cells and self-organizes endo-mesodermal progenitors through a network of morphogenetic signals (e.g., FGF, WNT, NODAL). Executing the simulation drives a synthetic HOX clock that patterns the emergence mesodermal cell fates (chordamesoderm, paraxial, lateral plate, extraembryonic). Synthetic perturbations introduced into the model simulate quantitative genetic and/or environmental influences on positional information to essentially ‘recode’ the mesodermal topography. This small working prototype model translates global or local perturbations to the system into mesodermal fate based on spatio-temporal colinearity of a synthetic HOX clock. This abstract does not necessarily reflect Agency policy.
URLs/Downloads:
DOI: Computational Embryology and Predictive Toxicology
IMAG_KNUDSEN_JULY_14_FINAL.PDF (PDF, NA pp, 7335.833 KB, about PDF)