CAREER: Characterizing germ granule diversity and its influence on germline development in Drosophila

Animal reproduction requires highly specialized cells that can pass on genetic information to the following generation. These cells, collectively known as the germline, contain cellular structures called germ granules, which house different types of biomolecules that are responsible for ensuring germline function. The overall research goal for this project is to understand how the contents of germ granules can be changed to influence animal development and reproduction. The experiments proposed will be performed within the included Education and Research Integration Plan which establishes New Jersey’s Research Alliance for Inclusive STEM Education. This new, three-phase program is designed to elevate research opportunities for students via multi-institution collaboration between local high schools, Kean University, and Princeton University. The proposal offers microscopy training and an outreach plan that uses biological images to promote enthusiasm about science throughout the community. Together, this project aims to shed light on mechanisms that can influence animal reproduction, supports the development of a competitive scientific workforce, improves education with hands-on research training and community engagement, and serves as a model for formalizing partnerships between high schools and research universities. Different Drosophila species display remarkable diversity in the abundance of certain transcripts that reside within germ granules. This project seeks to identify the mechanisms that control germ granule diversity and explore how such variations influence germline development and reproduction. The PI hypothesizes that diversity in germ granule mRNA content is cooperatively regulated by three mechanisms: differences in mRNA expression levels, variations in germ granules’ mRNA carrying capacity, and changes to the efficacy with which mRNAs become incorporated into granules. Aim 1 further characterizes germ granule diversity by quantifying the abundance in individual granules of mRNA from ten genes and comparing them across ten Drosophila species using single molecule in situ hybridization and quantitative imaging. Aim 2 combines biological data with computational modeling to measure the impact of each mechanism on germ granule mRNA content. The efficacy with which transcripts populate germ granules can be regulated by cis-acting elements in the 3′ UTR of each transcript. Using genome editing, Aim 3 investigates whether evolutionary differences within 3′ UTRs can alter germ granule mRNA content and germline development. Different classes of granules share similar components, and discoveries from this project may have broader implications for other types of biomolecular condensates. This award is co-funded by the Genetic Mechanisms Program in the Molecular and Cellular Biosciences Division and the Developmental Systems Program in the Integrative Organismal Systems Division. 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.