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How disordered proteins shape and regulate the genome

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We are familiar with the concept of disorder as the state to which we are inexorably driven according to the second law of thermodynamics. However, as Erwin Schrödinger observed, life, by definition, maintains a highly ordered state. This does not conflict with the second law as we have a ready source of free energy in the form of the Sun. Life’s ordered state is observable over many length scales, from the whole organism down to the very molecules from which it is made. The pandemic has educated us: the general public now knows what the spike protein on the SARS -CoV-2 surface looks like, and many are also aware of the successes of Deep Mind’s “AlphaFold 2” in predicting protein structures in silico. Everything appears to make sense: life’s complexity is explained by a sophisticated set of lego blocks. Structure dictates function. But what then of the 40% or more proteins in humans that do not adopt defined structures? Why are they made, what are they doing, and how does their lack of structure help? In this lecture, I will attempt to shed some light on this contradictory set of proteins, using examples from my group’s research into the condensation of DNA into liquid-like and fibre-like states, which is controlled by a set of highly disordered proteins.

This talk is part of the Kelvin club Michaelmas talks series.

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