Master regulators; from defining target networks to interpreting the impact of genomic variability on genome-wide activity

Transcription factors (TFs) are DNA-binding proteins which control the transcription – and hence expression – of their gene targets. The fate of a transcribed RNA as it proceeds from transcription to degradation is then largely determined by interactions with RNA-binding proteins (RBPs). TFs1s and RBPs3s each regulate hundreds to thousands of targets. TFs or RBPs are recruited to specific loci through recognition of specific features, such as sequence motifs, with these features widely dispersed across the genome/transcriptome. TFs and RBPs can collectively be considered master regulators (MRs). MR have fundamental roles in cell biology, and perturbed MR activity can contribute to disease aetiology. However, defining functional MR-target networks (interactomes) remains difficult.

I propose an innovative workflow to infer interactomes of all expressed MRs from large-scale transcriptomic datasets. My  key project goals will be to validate selected interactomes) exploit interactomes to interpret RNA signatures of selected disease and developmental paradigms, and explore how genomic variation affects MR activity at defined targets.

This project will seed numerous spin-off projects and generate substantial pilot data for future studies.