Project Reference: TRG27-GEN-FK2

Project title: Regulation of stem cell differentiation in vivo

Project outline

Our lab studies the germline, the immortal cell lineage that provides the continuity of life. Using Drosophila as a model, we combine developmental, genetic, microscopy, and genomic analyses (small RNA-seq, RNA-seq, Ribo-seq, ATAC-seq, Hi-C, long-read DNA- and RNA-seq) to build a systematic and unbiased understanding of the diverse aspects that govern germline biology in vivo. We are interested in dissecting the mechanisms protecting the genome against naturally occurring mutations as well as selfish DNA modules such as transposons (Gebert et al, Mol Cell 2021; Jansen et al, Genes & Dev 2024), and in using germline stem cells as a model for understanding stem cell self-renewal, growth, and differentiation in vivo (Gui et al, Cell Rep 2023; Grobicki et al, PNAS 2025; Samuels et al, Dev 2025). For the latter, we have developed a transgenic system to synchronise germline stem cell differentiation in vivo, which allowed us to uncover the transcriptional and translational programmes that underlie germline differentiation into oocytes (Samuels et al, EMBO J 2024). Surprisingly, gene expression changes did not accumulate linearly throughout the differentiation programme, but rather occurred in two distinct, developmentally sequential waves. While the first wave is characterised by the erasure of stem cell identity, the second wave, involving the rewiring of hundreds of genes, drives terminal differentiation, oocyte determination and entry into meiosis. This project aims to uncover the master regulators driving the second wave, as well as the mechanisms by which this is achieved. Our preliminary analysis suggests that the activation of the second wave mainly involves transcriptional changes, alternative transcriptional start site (TSS) usage, and epigenetic regulation. We will use genetic tools, genomics (ATAC-seq, ChIP-seq, Cut-&-Run, Hi-C), and microscopy to build a refined molecular understanding of how germline stem cells differentiate into oocytes in vivo.

Principal Supervisor

Professor Felipe Karam Teixeira

Email address: fk319@cam.ac.uk

Department / Partner Institute: Genetics

Website: https://karamteixeira.wixsite.com/website

BBSRC strategic theme

Understanding the rules of life