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.
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.
With Kévin Ricard, Jorge Fernández de Cossío Díaz, Andrea Pagnani & Clément Nizak, we develop models to predict and design antibody specificity.
With Angelo Charry & Clément Nizak, we analyze the relation between sequence and binding affinity at the scale of whole (Vh) antibody domains.
With Amaury Paveyranne & Clément Nizak, we develop an approach to measure, predict and engineer the specificity of serine proteases.
With Mats van Tongeren & Yannick Rondelez, we combine experimental evolution and machine learning to perform deep explorations in sequence space.