Regulation of dietary polyamine uptake in Drosophila melanogaster

膳食多胺促进动物健康衰老和长寿。因此，必须假设肠多胺摄取对于观察到的效果是关键的。然而，后生动物多胺转运的分子水平仍存在争议。在这里，模式生物黑腹果蝇将被用来确定转运蛋白（S）参与膳食多胺的摄取，并阐明其在多胺稳态，健康衰老和相关的表型，如肠道免疫衰老和肿瘤发生的作用。为此，我们将联合收割机结合果蝇的强大遗传工具箱，一种最近建立的全息培养基，允许在无多胺和限定的多胺补充条件下生长，以及果蝇细胞培养。调节蛋白抗酶是多胺摄取的假定抑制剂。反义酶的特征在于独特的进化保守的+1移码机制，其控制翻译过程，即，以多胺依赖的方式。利用转基因技术，对D.将在体内系统地研究黑腹果蝇抗酶，集中于促进长寿的条件，例如增加的膳食多胺水平、膳食氨基酸剥夺和减少的mTOR信号传导。在这种情况下，我们将解开D的作用。黑腹抗酶在膳食多胺吸收和衰老过程中的作用。膳食多胺的有益作用可能（部分）是由肠道微生物群的改变引起的。一个gnotobiotic方法将被用来研究这个问题在D。黑腹菌后生动物的多胺代谢是非常保守的。因此，我们的研究将最有可能导致更好地了解其他生物体（包括人类）的膳食多胺肠道摄取过程，并对药理学和老年学研究产生影响。

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.