A new approach to identifying the chemicals that harm us
How do the chemicals present in air, water, food and consumables affect us? The fact is that exposure to the thousands of chemicals – and their mixtures – used in consumer goods, agriculture, construction, manufacturing and the service industries can have a negative impact on people’s health. In recent decades, toxicologists have been trying to figure out how exposure to different chemical combinations affects us by investigating the molecular interaction between the chemicals and the proteins driving cellular functions. A research team supported by the EU-funded GOLIATH project has now developed a method to identify the proteins in our body that interact with the chemicals we are exposed to. Their research results have been published in the ‘Journal of Proteomics’. “Levels of pollutants are continuously increasing, and it is extremely difficult to test the effects of all chemicals. It is particularly difficult to test mixtures of substances,” notes lead author and PhD student Veronica Lizano-Fallas of GOLIATH project partner Linköping University, Sweden, in a news item posted on the university’s website. “I believe that our approach can lead to more efficient use of time and money than traditional methods, which test the effects on one biological mechanism at a time.”
Identifying protein targets
The new approach is a proteomics-based method called proteome integral solubility alteration (PISA). The researchers used PISA to identify soluble proteins in an organism that interact with the chemicals it is exposed to. To do this, they extracted a proteome – all the proteins that are or can be expressed by a cell, tissue or organism – from zebrafish embryos and then proceeded to analyse the identified protein targets. Four scenarios were used to assess the method’s utility: single chemicals, chemical mixtures, novel chemicals from marine biodiscovery, and new drugs. By studying the complete proteome of the zebrafish embryos under these four scenarios, the researchers were able to find more potential interactions between the chemicals and proteins. The PISA method can be used to spot the unfavourable biological effects of substances at an early stage. “Chemicals interact with proteins in a fairly promiscuous manner, and we often find that several proteins are influenced by the substances we test. We see that the functions of proteins are affected by their interactions with chemicals, which is consistent with the effects of pollutants and harmful substances in the cell,” remarks the study’s senior author Prof. Susana Cristobal of Linköping University in the same news item. The authors believe that the PISA assay has the potential to bridge the gap between molecular interactions and toxicity pathways. The 5-year GOLIATH (Beating Goliath: Generation Of NoveL, Integrated and Internationally Harmonised Approaches for Testing Metabolism Disrupting Compounds) project ends in December 2023. In addition to GOLIATH, the research also received financial support from the Marine Biotechnology ERA-NET project CYANOBESITY, another EU-funded project. For more information, please see: GOLIATH project website
Keywords
GOLIATH, chemical, protein, proteome, proteome integral solubility alteration, PISA
