Presenter: Nicholas Lammers (UC Berkeley)
Topic: Uncovering the kinetic fingerprints of transcriptional control using gene expression dynamics
Gene regulation is central to cellular function. Yet, despite decades of biochemical and genetic studies that have established a reasonably complete “parts list” of the molecular components required for eukaryotic transcription, we nonetheless lack quantitative models that can predict how these pieces interact in space and time to give rise to robust gene regulatory logic. For this talk, I will survey three distinct, yet interrelated projects from my Ph.D. that combine live imaging, computational methods, and theoretical modeling to dissect the molecular underpinnings of transcriptional control in the developing fruit fly embryo. To begin, I discuss results from a project that utilizes a novel statistical technique and live single-cell measurements of transcription to uncover how transcription factors modulate the
kinetics of the transcriptional cycle to produce a sharp stripe of gene expression. Next, I share recent results that utilize cutting-edge optogenetic methods to rapidly export repressor proteins from cells, revealing that transcriptional repression—and the development trajectories it dictates—is rapidly reversible. To close, I outline ongoing theoretical work that moves beyond phenomenological models of transcription to consider a molecular picture of how transcription factor binding transmits information to drive cellular decisions. These calculations reveal that non-equilibrium gene regulatory mechanisms, which require the expenditure of biochemical energy, may be necessary in order for gene loci to function in the context of crowded cellular environments.
