Exploring the molecular basis of increased egg production in Drosophila melanogaster induced by nutritive concentrations of lithium

• Applicant: Professor Dr. Gerald Rimbach
• Subject Area: Nutritional Sciences
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 534383576

Lithium has long been known as a bioactive substance. In pharmacological doses, it is used to treat neurological diseases and has been shown to promote mammalian somatic stem cell proliferation. However, it is still under debate whether nutritionally achievable concentrations of lithium exhibit beneficial bioactivity, which would point to an essential function. In our preliminary studies, we used Drosophila melanogaster to elucidate the impact of different dietary lithium concentrations on selected life history traits. We observed that a dietary lithium concentration of ≈0.7 mg/L was sufficient to significantly enhance the egg production of fruit flies by 30-35%, which was associated with a significant change in the transcript level of about 400 genes in the ovaries. In the anticipated DFG project, we will apply different feeding regimens to decipher nutritional aspects of lithium feeding with respect to egg production such as dose-dependency, reversibility, competitive inhibition by other metal cations, and transgenerational effects. These experiments shall also elucidate whether dietary lithium affects the age-related egg production decline and male fertility. Nutritive lithium level may induce changes in distinct steps of the oogenesis process. To address this point, we will determine the impact of dietary lithium on germline stem cells, germline progression, and ovulation mainly by microscopy methods. Our preliminary studies suggest that dietary lithium affects the insulin signaling pathway, GSK3/Sgg activity and octopamine signaling. By employing different genetic strategies including cell ablation, organ/tissue-specific overexpression/RNAi and mutant strains in combination with analytical and molecular biological methods we will investigate whether lithium interacts with these pathways. Of the 400 genes whose expression was changed in ovaries by ≈0.7 mg/L lithium, we have selected candidate genes. Their transcriptional response will be verified by qRT-PCR, before their expression pattern will be determined by reporter gene approaches. To evaluate their putative role in oogenesis, we will employ organ/tissue-specific overexpression/RNAi and mutant strains. Moreover, we will use in silico tools to identify putative transcription factor binding sites in the promotor regions of the 400 genes, which may lead us to the discovery of lithium-responsive transcription factors.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Kai Lüersen