About this project
The field of toxicology is being transformed by the development of new tools in molecular genetics, genomics and toxicogenomics. These new tools will be of great importance for the development of methods used to identify toxicological mechanisms. So far, few toxic compounds are understood at the mechanistic level and this hampers the understanding of biological responses to environmental exposures, including the effects of complex exposures, which are commonly occurring. With the genomic developments it is becoming apparent that many signaling pathways are conserved and that this will allow us to compare effects across species as well as improve the usefulness of model species in studying human health. Consequently a more precise extrapolation of effects between species in the environment and humans will lead to improved risk (analysis) assessments.
The goal of the project is to develop PCR based biological analysis tools for future use in environmental monitoring programs. The recent progress in gene sequence analysis has resulted in the availability of complete genome sequences for many species, opening up the area of comparative analysis to understand the mechanisms involved in toxic responses of organisms. This has thus made it possible to analyze the expression of whole genomes simultaneously. As the total genomes comprise of approximately 20-30.000 genes, depending on species, analysis of complete gene expression patterns remain complex, time consuming and expensive as it requires highly trained experts for the interpretation of how gene expression correlate to exposure scenarios. It is thus not realistic to use whole genome expression analysis as a tool in environmental monitoring programs. However, the development of focused gene expression analysis systems would facilitate their use in environmental monitoring programs. By selecting genes that are central to different physiological processes and disease conditions, we are developing systems where selected indicator genes are used to characterize the biological effects of environmental exposures.
1. Development of PCR arrays for selected species
Expected results: Focused tool for analysis of mechanisms and correlation between exposure and health
2. Validation of PCR array using dose-response exposures to selected toxicants.
Expected results: Gene profiles showing pathway dependent expression to selected treatments.
3. Field testing of PCR arrays.
Expected results: Feasibility of using PCR array under field conditions and to test waters obtained from contaminated sites and initial risk assessment.
El Marghani A, Pradhan A, Seyoum A, Khalaf H, Ros T, Forsberg LH, Nermark T, Osterman L, Wiklund U, Ivarsson P, Jass J, Olsson PE. 2014. Contribution of pharmaceuticals, fecal bacteria and endotoxin to the inflammatory responses to inland waters. Sci. Total Environ. 488-489:228-35