Project Details
Projekt
Consequences of TE dyshomeostasis and TE induced neurotoxicity on inflammation in C. elegans
Applicant
Professorin Dr. Julia Bornhorst
Subject Area
Nutritional Sciences
Term
since 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 316442145
Since trace elements (TE) occupy indispensable roles in several enzymatic reactions, imbalances of their homeostasis are supposed to be a risk factor for a broad range of diseases. TE have the capacity to modulate metabolic pathways known to be altered during aging, such as inflammatory and oxidative processes. Additionally, it is well-established that the homeostasis of single TE are regulated in a different manner under conditions of inflammation, but knowledge is still rare and the respective consequences for the aging organism are poorly understood. These gaps of knowledge will be addressed by the usage of the experimental model Caenorhabditis elegans (C. elegans). Comprising an ancestral immune system, studies on nematode immunity can be instructive in exploring TE roles in innate immune signaling. The reduced complexity of this model together with its genetic tractability allows a detailed characterization of the immune signaling cascade and consequence for the TE homeostasis in inflammatory conditions. Additionally, we will gain insights whether changes in the TE status hasten or aberrant aging and neuronal aging in the background of inflammation. Thereby age-specific, as well as inflammatory-specific TE combinations will be fed chronically to aging worms. The feeding conditions will be adapted in a way to result in systemic TE profiles which are comparable to the age-specific and inflammatory-specific TE profiles observed in the nematode and mouse studies. Due to the systemic interactions between innate immunity and other signaling systems, such as stress responses and mechanisms involved in the regulation of longevity, different endpoints including lifespan, age-related changes, oxidative stress and neurodegeneration will be assessed in the TE exposed worms. Since inflammation has been shown to play a role in the pathogenesis of neurodegenerative disorders worm models for neurodegenerative diseases will be used in order to characterize whether neuroinflammation results in an aberrant TE homeostasis. The worms will further be used to identify consequences of drug-based disease treatments on TE homeostasis since evidence suggests the interactions of aminoglycosides on the selenium (Se) metabolism. The identification of relevant biochemical pathways affecting TE metabolism and spotting consequences of inflammation and neuroinflammation will help to better understand age-related disease etiologies and might indicate the required optimal intake of the TE to maintain homeostasis in the respective pathology.
DFG Programme
Research Units
