Riccardo Ravasio

Postdoctoral Scholar, University of Chicago

Trained as a theoretical physicist on disordered systems and mechanical networks, I now combine non-equilibrium statistical physics and coarse-grained mechanistic models with high-throughput molecular biology to understand how complex traits such as error correction and new functions are acquired. I work with Arvind Murugan and Rama Ranganathan.

molecular evolution error correction directed-evolution platforms DNA polymerases

About

My first exposure to research was with Giulio Biroli, running Monte Carlo simulations of disordered systems and characterising how glassy systems jump energy barriers on their way to equilibrium. In my PhD, under the guidance of Matthieu Wyart, I used networks of springs as models for protein mechanics and identified architectural principles for the emergence of long-range response — or “action at a distance” — the allosteric regulation ubiquitous across proteins, suggesting how it can be evolved and designed. My exposure to experimental data during my PhD was mostly through protein crystallography. For my postdoc I wanted to move closer to evolution and possibly learn how to do experimental work myself. The collaborative environment at UChicago gave me a unique opportunity to learn how to do so, from cloning libraries to evolution platforms. I have since been working with Arvind Murugan and Rama Ranganathan on molecular evolution — from the evolution of error correction, such as proofreading in DNA polymerases, to how easily a protein can acquire new functions. Science aside, I am usually found with friends and my husband, gardening, throwing pots, cooking, taking photos or just out and about.

Selected Publications

2026

R Ravasio*, K Husain*, CG Evans, R Phillips, M Ribezzi-Crivellari, et al.. Evolution of error correction through a need for speed. Science 391 (6787), 818–824.

Biological processes across scales, from DNA replication to macromolecular self-assembly, have complex error correction machineries to fix errors introduced by forces of disorder, which otherwise would lead to loss of genetic information or cell death. Molecular machines like the ribosome and polymerases have evolved proofreading domains that double-check their progress at the cost of time and energy. We found that molecular processes pressured to go fast can evolve such complex error correction machinery, even without any pressure to avoid mistakes. This is because the insertion of a wrong component stalls the process and error correction makes everything faster by avoiding this time cost of stalls. Our findings suggest that life's earliest molecular machines could have stumbled onto error correction and thus achieved low error rates purely by racing against the clock.

2024

K Husain*, V Sachdeva*, R Ravasio, M Peruzzo, W Liu, BH Good, et al.. Direct and indirect selection in a proofreading polymerase. bioRxiv.

DNA polymerases span a wide range of error rates, from extremely accurate to error-prone. In stressful conditions a speed up of evolution from a larger error rate could be a beneficial strategy, but such mutators alleles also pay a cost, classically attributed to the deleterious load that comes with more errors. Using a viral-origin DNA polymerase replicating a cytosolic plasmid in yeast, we engineer an experimental system where the long-term benefit and short-term cost of a mutator allele can be tuned independently. We find that the dominant cost in this system is not deleterious load but a biophysical "more accurate is faster" trade-off in the polymerase itself: more mutagenic variants are also slower copiers, hurting the growth of their host cell. The conflict between immediate cost and delayed benefit produces unexpected dynamics: mutators that lose in every static environment can still win when selection sharpens on the right timescale.

2017

L Yan, R Ravasio, C Brito, M Wyart. Architecture and coevolution of allosteric materials. Proceedings of the National Academy of Sciences 114 (10), 2526–2531.

First of a series. Allosteric regulation is ubiquituos across proteins: the activity at one site is modulated by the binding of a molecule at a distant site. This work goes beyond an ad hoc explanation of how a given allosteric proteins work: we identify general architectural principles by which long-range mechanical response can emerge in elastic materials under selection. We show that elastic networks can be designed to be allosteric and display low-dimensional, soft elastic modes with characteristic structural signatures, suggesting a possible way for how allostery can be designed.

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Contact

rravasio@uchicago.edu · GitHub · LinkedIn