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The impact of germline metabolic reprogramming on reproduction and physiology

Project description

The role of metabolism on reproduction

Depending on their function, cells have different metabolic needs, and nutrient provision is secured through the diet. To ensure nutrient availability in the different tissues, the central nervous system is in constant communication with the body to determine tissues’ metabolic state and adapt the feeding preferences of the animal accordingly. Funded by the European Research Council, the SweetEggs project aims to investigate the mechanisms by which metabolic reprogramming impacts physiology and fertility, both at the cellular and the whole animal level. The project will use the fruit fly Drosophila melanogaster to address this question. The results will provide fundamental insight into the interplay between cellular metabolism and animal physiology and pave the way for nutritional interventions to tackle infertility.

Objective

Animals are composed of multiple tissues with different metabolic needs. During differentiation, the establishment of specific metabolic programs allows cells to acquire specialized functions. The nutrients that fuel these cell-specific metabolic pathways are obtained via the diet. In order to secure proper nutrient supply to these tissues, the central nervous system accesses their metabolic states, allowing the animal to mount behavioral strategies to adapt nutrient appetite. Our understanding of how cell-specific metabolic programs regulate animal physiology and behavior has been hindered by the lack of tractable experimental systems. Using Drosophila melanogaster I uncovered that the germline undergoes metabolic reprogramming, upregulating a specific carbohydrate metabolism branch, the pentose phosphate pathway (PPP) and that oogenesis progression requires the supply of dietary sugars, fueling this pathway. I further showed that the germline communicates its metabolic status to the fat body (FB), regulating the transcription of a satiety factor that acts on the brain to regulate sugar appetite. These findings represent a unique experimental platform, which I will use to study how cell-specific metabolic programs and nutrition regulate whole-animal animal physiology and fertility. I will: 1) identify the transcriptional factors regulating metabolic reprogramming in the germline; 2) test the requirement of specific PPP metabolites in germline cell functions and fertility; and 3) identify the molecules mediating the ovary-FB signaling axis and characterize their impact on FB transcriptional regulation, nutrient appetite, and fertility. Metabolic dysfunctions are known to result in many human conditions. This proposal will not only contribute to our understanding of how metabolism ensures reproduction, but will also help developing dietary interventions to tackle impactful human disorders including infertility.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-STG

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Host institution

FUNDACAO GIMM - GULBENKIAN INSTITUTE FOR MOLECULAR MEDICINE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 481 513,00
Address
AVENIDA PROFESSOR EGAS MONIZ
1649-035 LISBOA
Portugal

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Total cost

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€ 1 481 513,00

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