Research

Post-Translational Modifications - From Systems to Mechanisms

Life is stressful, however, cells have the capacity to adapt. They are constantly responding to a wide range of internal and environmental signals. How? Post-translational modifications (PTMs) regulate protein function within seconds to minutes, altering their activity, localization or interacting partners. In recent years, thousands of PTM sites have been identified thanks to revolutionary advancements in quantitative mass spectrometry-based proteomics. However, what is the function of all these PTMs and how they interplay to regulate biological processes is vastly unknown.  Functional studies have been lagging behind due to methodological limitations.

Recently, I led the development of an approach based on reverse genetics and chemical genomics to study the function of phosphorylation sites at scale in yeast (Viéitez C, Nature Biotech 2022). This was for the first time proof of the pervasive functional importance of phosphorylation on protein function. Now, in my group, by expanding our method and in combination with other cutting-edge high-throughput approaches, we aim to functionally study the role of PTMs in the regulation of chromatin functions using S. cerevisiae as a model organism. For biologically relevant candidates, mechanistic work will follow using molecular biology and biochemistry techniques.

Figure 1. Signal transmission from the membrane to the nucleus through signalling cascades by the quick and regulated action of protein PTMs.

Figure 2.  Schematic representation of a high-throughput phenotypic screen based on reverse genetics and chemical genomics.

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