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FRIPRO-Fri prosjektstøtte

HE-POP: Studying the Health Effects of Persistent Organic Pollutants, Using Mass Spectrometry, Organoids, and Organ-On-A-Chip

Alternative title: HE-POP: Bruk av massepspektrometri, organoider og organ-on-a-chip for å undersøke helseffekter av persistente organiske miljøgifter

Awarded: NOK 8.0 mill.

Per- and polyfluoroalkyl substances (PFAS) is a large group of manmade fluorinated chemicals that are thought to affect our organs negatively. Sources of PFAS can be the production of water-, heat-, and stain-resistant products, and these chemicals are a part of our everyday life. The complete understanding of how certain PFAS affects biological systems is not clear. Some PFAS might increase the risk of developing Non-Alcoholic Fatty Liver Disease (NAFLD) and increase the risk of diabetes. To understand how PFAS affects our organs, we want to use tiny lab-grown versions of organs called organoids. These miniature organs can be created from human stem cells and offer a controlled setting to study how PFAS affect our liver and pancreas without involving animals. To study health effects, we must be able to monitor levels of biomolecules such as lipids in the liver and hormones in the pancreas. To do that, we will develop analytical tools to measure the effects. The biochemical (proteins and metabolites) profile of liver organoids will be compared to PFAS-exposed organoids. We will then expand the analytical toolkits to examine which metabolic pathways are affected and if the effect is the same in NAFLD-induced and PFAS-exposed organoids. We will also expose pancreatic islet organoids (insulin-producing) to PFAS to examine the effect of PFAS exposure on hormone production in relation to diabetes. When the effects of PFAS exposure on liver and pancreas organoids are established, the organoids will be co-cultivated on chip and the effects of PFAS exposure will be examined and compared to individual, untreated organoids.

Persistent organic pollutants (POPs) are believed to contribute to metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and type 1 diabetes. HE-POP aims to investigate the effects of per- and polyfluoroalkyl compounds (PFAS), a type of POPs), on organ function in a controlled environment. Organoids are multicellular laboratory-grown miniature organs, that are grown from stem cells. HE-POP will use organoids to examine how PFAS affects our organs and develop cutting-edge bioanalytical tools and methodology to measure these effects using liquid chromatography-mass spectrometry. HE-POP hypothesizes that PFAS negatively affects organ function, as evidenced by changes in hormone and lipid levels characteristic of NAFLD and type 1 diabetes. Organoids offer a controlled environment to study the effects of PFAS on the liver and pancreas, without the use of animal models. HE-POP aims to gain evidence of the negative effects of PFAS on organ function through controlled experiments on organoids and aid in understanding the biological mechanisms underlying NAFLD and type 1 diabetes. HE-POP has fundaments in UN sustainable development goals, specifically #3, #12, and #14/15, seeking an understanding of diseases with worldwide prevalence, and understanding how POPs affect our life and surroundings and help enable the right regulatory actions and replacement chemicals.

Funding scheme:

FRIPRO-Fri prosjektstøtte