Cells are constantly responding and adapting to a wide range of internal and environmental signals. Post-translational modifications (PTMs) offer an efficient mechanism to regulate protein function within seconds to minutes. In recent years, significant advancements in quantitative mass spectrometry-based proteomics have revolutionized the systematic analysis of PTMs allowing the identification of thousands of PTM sites in a single study, with phosphorylation and acetylation among the most studied ones. However, the functional study of these PTMs and their regulation has been lagging behind due to methodological limitations. Recently my former colleagues and I developed 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). Now is the time to leverage this approach to address longstanding questions in the fields of cell signalling and chromatin: which PTM sites are functionally relevant and how are they regulated in a context-specific manner?

Our research group focuses on studying the functional significance of protein Post-Translational Modifications (PTMs) in the regulation of signalling and chromatin in yeast by combining cutting-edge high-throughput approaches and molecular biology techniques.

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

How we do it

Recently my former colleagues and I developed 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 2. Eschematic representation of a high-throughput phenotypic screen based on reverse genetics and chemical genomics.