Dr. Valery Forbes

This project involves modeling data in connection with an NSF-funded project (Collaborative Research: URoL: Epigenetics2: Epigenetic pathways to regulate homeostatic resilience: Model-based discovery of rules across diverse mammals UMN #00084593). The researchers plan to run simulations through MSI using an agent-based model with NetLogo software. Their model simulates the inner dynamics of an animal cell, including its genomic interactions and how these influence cell morphology and physiology. The central aim is to use this model to identify how organisms respond to environmental stressors at the cellular level, and how this response varies across species. In the model, agents are regulatory elements and genes, and are able to impact the behaviors of each other. Rather than imposing rules for these interactions among agents, the researchers will begin with randomized sets of rules and calibrate the model based on empirical data of cellular responses to stress. They will apply a common-garden framework to cultured cells from 16 mammalian species, which will yield genomic data and measures of cell morphology and physiology when exposed to different levels of temperature, glucose, and oxygen. These species include humans, dolphins, bats, and camels, among others, which vary in how they respond to environmental stressors, offering a comparative approach for identifying mechanistic rules whereby cells achieve robustness to environmental stressors. Calibration of the model will involve iteratively selecting for rules that best lead to the emergent outcomes observed in the cellular assays. The model is generalized for any species, any cell type, and any environmental stressor, offering many applications of the model beyond this study. This study will increase understanding of how organisms mitigate environmental stressors at the cellular level such that researchers can better address how organisms are impacted by and respond to extreme environmental conditions.