Mechanisms of sexual dimorphism in infection-induced iron sequestration in Drosophila melanogaster

• Applicant: Dr. Igor Iatsenko
• Subject Area: Cell Biology ; Animal Physiology and Biochemistry ; Immunology ; Systematics and Morphology (Zoology)
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495271245

Males and females of a species respond differently to the prevalence and pathogenesis of infectious diseases. While this is a well-documented phenomenon, conserved across species, in most cases we do not know the precise mechanisms mediating such sexual dimorphism. Such lack of knowledge is partly because sex as a biological variable has not been considered in the analysis of outcome data. Considering known differences between males and females in iron metabolism, differences in the efficacy of iron sequestration during infection can be one of the mechanisms responsible for sexually dimorphic infection outcomes. However, direct causal relationships between dimorphism in iron sequestration and susceptibility to infections are lacking. This project aims to investigate whether and how sexual dimorphism in iron-sequestration affects the infection outcome using Drosophila melanogaster as a model. Our previous work and preliminary results identified Transferrin 1 as a key protein mediating iron sequestration during infection in Drosophila. Importantly, Tsf1 is expressed at a higher level in female flies that are also more resistant to Pseudomonas aeruginosa infection. These results raise a hypothesis that sexual dimorphism in iron sequestration is responsible for the sexually dimorphic infection outcome. In this project, we will test this hypothesis using several approaches, including Drosophila genetics, iron quantification, transcriptomics, and functional genetics. The results of this project will provide answers to several important questions, namely: 1) is iron sequestration during infection sexually dimorphic? 2) if so, does Tsf1 mediate such dimorphism? 3) are there any additional mechanisms beyond iron sequestration that mediate sexual dimorphism in response to infection? Our study by addressing the role of iron sequestration in the dimorphic infection outcome in Drosophila will advance our knowledge on the mechanisms of the sex differences in nutritional immunity some of which can apply to other animals. More broadly, identifying factors responsible for sex differences in immunity is also an essential step towards the development of optimal disease management strategies for both sexes.

• DFG Programme: Research Grants