Kinetic modelling and spatially resolved chemical analysis to explore dose-at-target during early development (DOSEARLY)

This project aims at developing and validating computational models for assessing exposure of organic pollutants during critical developmental stages in vital target tissues of zebrafish.

In particular, we aim to advance current physiologically based kinetic (PBK) models by combining tissue mass spectrometry imaging using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MSI) with machine learning and Bayesian statistics.

A PBK model is a representation of an organism with tissues and blood flows where chemicals are allowed to distribute driven by their intrinsic chemical properties reflected in partitioning coefficients, and uptake and excretion rates.

MALDI-MSI provides an opening to generate tissue-specific data for model training and validation whereas advanced modelling will be used to derive and calibrate required model parameters.

Zebrafish will be studied over critical developmental periods of life including embryonic, larvae, juvenile, and adult life stages.

The project will be coordinated by professor Patrik Andersson, with expertise in computational methodologies for effect and fate studies of chemical pollutants.

Co-applicants are professor Pim Leonards, environmental analytical chemist, and Dr Stefan Örn, expert in zebrafish toxicity testing.

The project will provide novel models and increased understanding on chemical drivers of absorption, distribution, metabolism, and excretion processes of chemicals during critical windows of development.