Experimental protein evolution

The basic elements of evolution – selection/amplification/mutations – can be reproduced in the lab. But how to navigate the gigantic sequence space?

Evolvability of antibody frameworks

Are all proteins equally likely to generate selectable variations through mutations? We have developed an approach to measure such differences in antibodies, proteins that may be especially evolvable because undergoing an evolutionary process (affinity maturation) is part of their physiological role. We performed experimental selections of minimal anibody libraries by phage display and quantified the results by high-throughput sequencing, showing that differences in selective potentials can be identified, consistent with a special aptitude of germline antibodies.

References:

• S. Boyer, D. Biswas, A. K. Soshee, N. Scaramozzino, C. Nizak, O. Rivoire (2016). Hierarchy and extremes in selections from pools of randomized proteins.

• S. Schulz, S. Boyer, M. Smerlak, S. Cocco, R. Monasson, C. Nizak, O. Rivoire (2021). Parameters and determinants of responses to selection in antibody libraries.

Inference and design of specificity profiles

We show how to combine experiments where the same antibody library is selected to bind different ligand combinations to learn the parameters of a physical model that identifies the contribution of each ligand to selection. This enables the inference of hidden epitopes and the design of antibodies with novel specificity profiles.

Reference:

• J. Fernandez-de-Cossio-Diaz, G. Uguzzoni, K. Ricard, F. Anselmi, A. Pagnani, C. Nizak, O. Rivoire (2024). Inference and design of antibody specificity: from experiments to models and back.