Research interests
EvoMorph - Evolution & Morphogenesis in molecular systems EvolutionPresentation
I am trained in theoretical physics, with a specialization in statistical mechanics and complex systems.
Currently, I am working on a project that aims at modeling genotype-phenotype relations in biomolecules. In particular, my goal is to explain how biophysical properties emerge as a result of complex interactions between components of these systems (e.g. long-range interactions between amino acidic residues in proteins).
The model system of choice is a family of proteolytic enzymes called serine protease [1], which has been studied for a long time by biochemists but its internal mechanisms have not yet been well understood. The biophysical property of interest is their specificity profile, which is heterogeneous and cannot be exhaustively explained just in terms of geometrical / chemical properties (i.e. short-range interactions) [2].
I use a set up that allows for high-throughput [3] and low-throughput measurements, that combines tools from bioinformatics, droplet microfluidics and molecular biology. These data can in turn be used to train machine-learning models that can capture coevolutionary signals and are also able to generate artificial proteins with the desired biophysical properties [4, 5].
[1] Hedstrom, Lizbeth. "Serine protease mechanism and specificity." Chemical reviews 102.12 (2002): 4501-4524.
[2] Gráf, László, et al. "Electrostatic complementarity within the substrate-binding pocket of trypsin." Proceedings of the National Academy of Sciences 85.14 (1988): 4961-4965.
[3] Romero, Philip A., Tuan M. Tran, and Adam R. Abate. "Dissecting enzyme function with microfluidic-based deep mutational scanning." Proceedings of the National Academy of Sciences 112.23 (2015): 7159-7164.
[4] Russ, William P., et al. "An evolution-based model for designing chorismate mutase enzymes." Science 369.6502 (2020): 440-445.
[5] Halabi, Najeeb, et al. "Protein sectors: evolutionary units of three-dimensional structure." Cell 138.4 (2009): 774-786.
Topics
- Machine learning on protein sequences
- Droplet microfluidics
- Next Generation Sequencing (Nanopore)
Experimental Platform
- DNA and Plasmids Purification
- Gel Extraction
- Beads Purification for NGS
- NGS through ONT (Flongle)
- Cloning and Transformation (E. coli and B. subtilis)
- PDMS Microfabrication for Microfluidics
- Microfluidics for droplet sorting
- Fluorescent plate assays of enzymatic activity
Active collaborations
Olivier Rivoire (ESPCI - Paris), Sean Quigley, Rama Ranganathan (UChicago), Lorenzo Rosset, Martin Weigt (CSQB - Paris), Francesco Zamponi (Sapienza - Rome).
