Ecology and Evolution Seminar #7: "Quantitative models of enhancer regulatory function in the Drosophila embryo" by Garth Ilsley

It is difficult to reason about gene networks or how they change over time without the use of simplifying models. The gene regulatory models commonly used by biologists show gene nodes with multiple inputs that are either activating or repressing. These models are useful for summarising the results of single input perturbation experiments (e.g. gene knockout mutants), but they come with restrictive assumptions, which I will describe in my talk. More complex biophysical models circumvent these limitations, but the complexity of these models makes them difficult to reason with and, moreover, they are often poorly predictive of even single input perturbations.

I will highlight an alternative approach that can accurately predict changes in the concentrations of gene regulatory inputs, including gene knockout mutants and ectopic expression of transcription factors, shown for a few enhancers in Drosophila.  Further, without explicit biophysical parameters, these model results can be related directly to hypotheses regarding loss and gain of binding sites, both theoretically and experimentally. Correspondingly, these models provide a framework for the quantitative control of enhancers with engineered transcription factors, which I will illustrate by example.