Detalle de: Structural Systems Biology

The cellular interior is not a mere Brownian soup of molecules; it is rather an exquisitely structured entity organized into hierarchical levels. Knowing how proteins assemble into different layers of organization, is thus fundamental to understanding the functioning of the cell.

We recently demonstrated that proteins are a few mutations, sometimes even one mutation away, to form infinite polymers –aka supramolecular assemblies– (Garcia-Seisdedos, et al. Nature 2017, Empereur-Mot, Garcia-Seisdedos, et al Sci Data 2019, Garcia-Seisdedos, et al PNAS 2022). They are amorphous or ordered structures resulting from the self-assembly of folded proteins.

In recent years a growing number of studies have identified proteins that naturally (often in a condition-dependent manner, e.g. membrane-less organelles), or as a result of mutation, form supramolecular assemblies, suggesting important implications in cellular adaptation and disease.

Although it is a widespread phenomenon that is shifting the way we see the proteome organization, supramolecular assembly remains poorly understood. Its characterization will bring about important advances with implications in evolution, disease, and protein design.

The research of the lab is at the interface of Structural, Cell, and Systems Biology and aims to understand the process by which proteins form supramolecular assemblies in the cell, as well as its role in cellular organization, adaptation, and disease. To address these aims, we combine the power of yeast genetics and high-content microscopy with biophysical and structural techniques.

Figure adapted from Garcia-Seisdedos H, et al. Nature 2017

https://www.nature.com/articles/nature23320