Chromosome structure and dynamics

Protein Phosphatases in Chromatin Organisation

Reversible protein phosphorylation is one of the major mechanisms used by cells to control biological processes in space and time and to respond to environmental stimuli. A healthy situation is when cells can balance the level of protein phosphorylation (mediated by kinases) and de-phosphorylation (mediate by phosphatases) by regulating these binary switches.A great deal of research has been conducted to discover disease-relevant kinases with the ultimate goal of designing molecules that can control their activity. However, despite the equal importance of phosphatases in these systems, the knowledge and discoveries on phosphatases have lagged behind. This is mainly due to the lack of basic knowledge of their structure and regulation.    Recent discoveries on protein phosphatases have changed the game and have opened new avenues towards the understanding of these enzymes and their potential use as therapeutic targets.

In human cells, Protein Phosphatase 1 (PP1) and Protein Phosphatase 2A (PP2A) account for 90% of all serine/threonine phosphatase activity in most tissues and their malfunction is associated with a variety of diseases.

The activity and specificity of phosphatases is highly regulated in space and time and it is achieved with the help of other proteins (regulatory subunits) that activate/inhibit or direct the phosphatases function towards specific targets. Therefore understanding how this occurs represents one of the priorities in the field.

My laboratory is interested in understanding how our genomes are maintained in a stable state throughout our lifespan and how they can respond correctly to external stimuli. Therefore our aim is to identify which phosphatases are important for genome maintenance.


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