Regulation of dietary polyamine uptake in Drosophila melanogaster

• Applicant: Professor Dr. Kai Lüersen
• Subject Area: Nutritional Sciences
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 317469350

Dietary polyamines promote healthy ageing and longevity in animals. Accordingly, one has to assume that the intestinal polyamine uptake is critical for the observed effects. However, the molecular level of metazoan polyamine transport is still under debate. Here, the model organism Drosophila melanogaster will be used to identify transporter(s) involved in the uptake of dietary polyamines and to elucidate their role in polyamine homeostasis, healthy ageing and related phenotypes such as intestinal immunosenecence and tumorigenesis. To this end, we will combine the powerful genetic tool box of the fruit fly, a recently established holidic medium that allows the growth under polyamine-free and defined polyamine supplementation conditions and Drosophila cell culture. The regulatory protein antizyme is a putative inhibitor of polyamine uptake. Antizymes are characterized by a unique evolutionary conserved +1 frameshifting mechanism that controls the translational process i.a. in a polyamine-dependent manner. By using transgenic strategies, the expression control of D. melanogaster antizyme will be systematically investigated in vivo focusing on longevity-promoting conditions such as increased dietary polyamine levels, dietary amino acid deprivation and reduced mTOR signaling. In this context, we will unravel the role of D. melanogaster antizyme in the uptake of dietary polyamines and the ageing process. The beneficial effects of dietary polyamines may be (partly) elicited by alterations in the intestinal microbiota. A gnotobiotic approach will be employed to examine this issue in D. melanogaster. The metazoan polyamine metabolism is well conserved. Hence, our studies will most probably lead to a better understanding of the intestinal uptake process of dietary polyamines in other organisms including humans with impact on pharmacological and geriatric research.

• DFG Programme: Research Grants