Postdoctoral Fellowship: PRFB: Area 1: Modeling gene drive with selfish germline stem cells in the Drosophila testis

Hodge, Rachel, New York NY

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2024, Broadening Participation of Groups Underrepresented in Biology. The Fellowship supports a research and training plan for the Fellow that will increase the participation of groups underrepresented in biology. Selfish elements are genes that provide germline stem cells (GSCs), which produce sperm in males, with a competitive advantage over their neighbors. This allows GSCs to transmit their genes at an exceptionally high rate, known as gene drive, but regulation of gene drive remains poorly understood. Mutations in the gene chinmo act as a selfish element in GSCs from male fruit flies. The Chinmo protein binds DNA to change expression of specific genes, although how Chinmo is regulated and how it binds DNA are unknown. Defining these mechanisms will benefit our understanding of gene drive, which has relevance to evolution, ecology, and population genetics. The fellow will perform outreach on the behalf of the National Postdoc Association in their advocacy and diversity branches. It is known that chinmo-mutant GSCs remodel the extracellular matrix (ECM) to outcompete wild-type neighbor GSCs. The fellow hypothesizes that the chinmo-mutant allele causes gene drive due to dysregulation of direct Chinmo target genes, whose identities are unknown. First, the fellow will use CUT&RUN to identify Chinmo binding sites on chromatin, and RNAseq following Chinmo depletion to identify transcriptional targets in GSCs. Candidates will be prioritized for further study based on robustness of peaks and transcriptional changes upon Chinmo loss, and assessed for their role in ECM remodeling and GSC competition. Second, the fellow has identified three transcription factors that when depleted from GSCs also remodel the ECM. This suggests that they regulate cell competition as Chinmo co-factors. The fellow will investigate these three genes for their roles in GSC competition and gene drive using clonal assays. The fellow will use CUT&RUN and RNAseq to assess if these transcription factors share common target genes with Chinmo. Completing the proposed research will train the fellow in genomic techniques and clonal analyses, as well as in the topics of cell competition, gene drive, and gene regulation. The fellow will volunteer at UCLA, which aims to be certified as a Hispanic-Serving Institution by 2025, by participating in alumni career panels to promote the retention of postdocs. 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.