Nigel Groome Studentship: Unravelling Context-Specific Hormonal Control of Gene Expression in Drosophila

The regulation of gene expression underlies nearly every biological process in eukaryotes. It is facilitated through transcription factors (TFs), which bind to DNA and influence mRNA production at target genes. Organism-wide changes in gene regulation are often coordinated by hormones; however, their effects can be highly tissue -specific, raising the question of how a systemic signal is translated into a cell-specific one.

Some hormones act via nuclear receptors, proteins that combine the functions of receptor and TF in a single molecule. The deployment of different nuclear receptor isoforms and co-factors likely plays an important role towards their specificity. However, the precise molecular mechanisms remain elusive.

In this project, we plan to use the power of Drosophila melanogaster as a model to better understand context-specific control of gene expression through nuclear receptors. We will focus particularly on development of the central nervous system and the fly genitalia.

You will use advanced fly genetics and high-resolution confocal imaging of fixed and live tissues to reveal context-specific dynamics of nuclear receptor isoforms and known co-factors. Using next-generation sequencing (RNAseq and CUT&RUN), you will uncover target genes and genome-wide binding in different tissues.

Bioinformatic analysis of binding sites will reveal potential novel interaction partners, which can be further analysed. Additionally, you will study phenotypes after tissue-specific removal of nuclear receptor isoforms. A
special focus will be on genital morphology, connections in the nervous system (NS), and behaviour (using AI-based video annotation).

Training and supervision will be provided by Daniela Santos Nunes, who uses fly genital morphology as a model for evolutionary change, Sebastian Kittelmann, an expert in the use of multi-omics to understand gene regulation, and Darren Williams (King’s College London), who is experienced in hormonal control of NS  development.