Utveckling av bananflugan som modellsystem för att ersätta kort och långtidsundersökningar av blandningar av miljögifter på gnagare

Tidsperiod: 2015-01-01 till 2017-12-31

Projektledare: Helgi Schiöth

Medarbetare: Michael Williams, Madeleine Le Greves, Madeleine Le Grevés

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 2 040 000 SEK

Toxicology testing is one of the main reasons for use of experimental animals. We set up a productive fly (Drosophila) lab, with a range of methodologies, enabling detailed molecular, physiological and behavioral studies. This project aims to develop the fly model to enable cost effective determination of short and long term effects of a large range of environmental toxin mixtures. This will allow for replacement and reduction of the need for rodent toxicology testing. We have discovered that several environmental toxins, Bisphenol A (BPA), Bisphenol A diglycidyl ether (BADGE), Dibutyl phthalate (DBP), and Di(2-ethylhexyl) phthalate (DEHP), disrupt key metabolic functions when fed to the fruit fly. We demonstrate that flies exposed to BPA are unable to undergo normal lipolysis and that BADGE or DBP make them starvation resistant. Furthermore, we determined that BPA and DBP are able to disrupt highly conserved insulin-glucagon-like hormonal signaling in the fly. We have a range of genetic tools at our disposal, including the use of optogenetics to detect neurosecretory signals and neurotransmitter signaling. These models are very promising to replace and reduce the number of rodents in screening for toxins disrupting endocrine signaling. The team behind the application has very productive within pharmacology and toxicology research and previous research has resulted in number of high impact publication and high number of citations.