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Mathematical modeling of a novel in vitro system for measuring permeation of hydrophobic and volatile chemical across a fish intestinal epithelial cell monolayer
Permeation of organic chemicals from the aquatic environment across cellular barriers is a critical step for accumulation in organisms, such as fish. To better understand the underlying processes, we aim to study the role of the fish intestine as barrier for hydrophobic and volatile chemicals. There
Keywords: mathematical model, ecotoxicology, in vitro
Permeation of organic chemicals from the aquatic environment across cellular barriers is a critical step for accumulation in organisms, such as fish. To better understand the underlying processes, we aim to study the role of the fish intestine as barrier for hydrophobic and volatile chemicals. Therefore, at the department of environmental toxicology, we combined a recently developed in vitro epithelial barrier model using the rainbow trout (Oncorhynchus mykiss) intestinal cell line, RTgutGC, and a newly constructed chamber that enables stable chemical exposure concentrations.We estimated the effective permeation of different chemicals across the intestinal epithelial monolayer and measured chemical mass in different biological and non-biological compartments of the system over time. Mathematical modeling of the experiment is now needed to determine which processes (passive diffusion, carrier-mediated influx/efflux, binding, biotransformation) are dominant for the measured chemicals and what are their corresponding rates.
METHODS: The candidate will use Matlab to build the models and perform parameter estimation, identifiability analysis and model selection, using algorithms available at the department for environmental toxicology. In case of extensive expertise of the student, shifting to a different modeling environment is an option.
Permeation of organic chemicals from the aquatic environment across cellular barriers is a critical step for accumulation in organisms, such as fish. To better understand the underlying processes, we aim to study the role of the fish intestine as barrier for hydrophobic and volatile chemicals. Therefore, at the department of environmental toxicology, we combined a recently developed in vitro epithelial barrier model using the rainbow trout (Oncorhynchus mykiss) intestinal cell line, RTgutGC, and a newly constructed chamber that enables stable chemical exposure concentrations.We estimated the effective permeation of different chemicals across the intestinal epithelial monolayer and measured chemical mass in different biological and non-biological compartments of the system over time. Mathematical modeling of the experiment is now needed to determine which processes (passive diffusion, carrier-mediated influx/efflux, binding, biotransformation) are dominant for the measured chemicals and what are their corresponding rates.
METHODS: The candidate will use Matlab to build the models and perform parameter estimation, identifiability analysis and model selection, using algorithms available at the department for environmental toxicology. In case of extensive expertise of the student, shifting to a different modeling environment is an option.
The aim of the master project is to build a family of mathematical models that describe the permeation experiments, use model selection to find the dominant processes in the experiments with different chemicals and use the best fitting models to estimate the effective permeation coefficient.
The aim of the master project is to build a family of mathematical models that describe the permeation experiments, use model selection to find the dominant processes in the experiments with different chemicals and use the best fitting models to estimate the effective permeation coefficient.