The control of gene transcription is the main regulatory step for cellular gene regulation. Previous work from the Panne laboratory has revealed mechanistic and structural insights into how the interplay between cellular signalling and transcription factor (TF) activation, controls the function of p300, a key transcriptional co-activator (Ortega et al., Nature 2018). Here we aim to address how co-assembly of p300 with TFs controls assembly of defined enhancer complexes and recruitment of the general Polymerase machinery. Recent developments in cryo EM and advances in the structural understanding of RNAPII and the Preinitiation complex (PIC) now make it realistic to study the entire process of transcription activation at a mechanistic/structural level. We propose an interdisciplinary project which will involve biochemical and structural studies by cryoEM together with single-molecule visualization, in real-time, of the dynamics of enhancer complex assembly and control of the PIC machinery during transcription initiation.
Academic entry requirements: UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.