CAREER: Regulation of Drosophila melanogaster oogenesis by ovarian and adipose tissue amino acid sensing signaling pathways

This CAREER project investigates how fat tissues and reproductive organs communicate and coordinate fat storage and utilization in relationship to oocyte production and nutritional status. A complex network of inter-organ communication underlies whole organism physiological responses to dietary input dynamics. There is a clear association between dietary input and reproduction, wherein suboptimal nutritional conditions, such as malnutrition and obesity, negatively impact fertility.

Specifically, fat cell dysfunction associated with diet-induced obesity leads to aberrant egg or oocyte production in organisms ranging from insects to humans. However, the fundamental principles linking nutritional physiology with oocyte production are not completely understood. Using the fruit fly Drosophila melanogaster as a model organism, results from this work will uncover how ovarian and fat tissues sense, respond to, and communicate about dietary input.

Overall, this study will advance understanding of the role that multi-organ nutrient sensing plays in the organismal response to dietary changes. In addition to the research goals, a Columbia, South Carolina, community outreach program centered around the nutrient sensing research theme will be developed for K-12-aged children and their caregivers. The program will consist of hands-on activities that provide practical experience with science and engineering practices, as well as exposure to pathways to careers in biological research.

The leaders of the research activities will receive valuable training in effective scientific communication.

In Drosophila melanogaster, direct nutrient sensing by the ovary and remote nutrient sensing by the adipose tissue regulate oogenesis; however, the different modes of amino acid sensing used are not fully understood. The overall goal of this work is to uncover the cellular and molecular mechanisms that mediate dietary protein sensing and communication.

This work leverages the power of D. melanogaster genetics to perturb the amino acid response pathway, a branch of the integrated stress response that senses limitations in amino acids, in specific ovarian cell types, to assess its currently unknown role in oogenesis. Additionally, a targeted candidate approach will be taken to identify adipocyte-derived factors that function downstream of the amino acid response pathway and mechanistic Target of Rapamycin (TOR) signaling to regulate ovarian germline stem cell maintenance and ovulation, respectively.

Taken together, this project will define the molecular mechanisms that govern amino acid sensing in and communication between ovarian and fat tissues. A post-doctoral fellow and both graduate and undergraduate students will participate in the research.

This project is jointly funded by the BIO-IOS-Physiological Mechanisms and Biomechanics Program, the BIO-IOS-Animal Developmental Mechanisms Program, and the Established Program to Stimulate Competitive Research (EPSCoR).

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.