The cell is densely populated by tens of thousands of proteins, which have leading roles in defining the phenotype. Cell phenotype is tightly regulated by epigenetic mechanisms, driving the formation of specialized tissues even though all the cells of an organism share the same DNA. In particular, histone proteins and their interactors modulate DNA readout by binding and folding chromatin. This regulation is mostly driven by catalyzing post-translational modifications (PTMs) on histones themselves. Histone PTMs affect gene expression regulation, DNA repair, chromatin compaction, and they lead to aberrant phenotypes when improperly regulated. However, we are still far from confidently defining how chromatin dynamics defines our phenotype. Our lab develops and exploits methods based on mass spectrometry to identify and quantify not only histone marks, but also how chromatin fine-tuning is assessed and how this can be edited for fitness. More specific projects are:


Chromatin compaction

We use metabolic labeling to discriminate open from closed chromatin. By using this type of labeling, we can define whether histone modifications occupy active chromatin domains or heterochromatin. We use this method to predict biological functions of histone marks, and especially define the state of a gene carrying both active and repressive histone marks.


Cross-talk of histone modifications

We are highly invested in developing strategies to understand why multiple modifications co-exist on a histone (or in general a protein). Which modifications co-exist, how abundant are they, and what happens to the chemical properties of the protein? We are convinced that answering these questions will pave the way to unravel the fine-tuning of a cell that allows such high complexity.


Affordable proteomics

Part of our legacy is also to bring proteomics closer to routine applications. To do so, proteomics needs to become simpler and possible using a cost effective workflow. We are collaborating with the company Veritomyx to exploit data produced by a cheap but most versatile mass analyzer, the ion trap. Performing proteomics with an ion trap mass spectrometer will allow many laboratories to afford this type of analysis, making this discipline a routine application in biology.