Variety is the spice of life: Why cells differ in their redox status


The cellular redox status has long been linked to many different cellular functions and behaviors, including protein homeostasis and aging. Accordingly, the cell has developed highly regulated systems that contribute to the maintenance of both the global redox status and protein homeostasis at large. Changes to these systems have been found to correlate with cellular aging, raising intriguing questions as to the source of the redox-associated aging process itself and the molecular switches which may control it.

Here, we present a novel methodology to identify and characterize a redox-dependent heterogeneity within yeast cells, using the redox-sensitive probe Grx1-roGFP2. Using our methodology, we were able to sort populations according to their oxidative status, defining their growth properties, as well as their proteomic and transcriptomic profiles. From this, we further identified three key proteins (Hsp30, Dhh1, and Pnc1) which affect basal oxidation levels and may be viewed as potential effectors of the redox status at large. This methodology may open the door for significant future research into redox-associated factors and the mechanisms behind redox-dependent heterogeneity.


eLife 2018, Current Genetics 2018
The role of protein plasticity in chaperone function

We are exploring a novel class of chaperones, which are activated by specific stress conditions (e.g., oxidative stress) that lead to the inactivation of main housekeeping chaperones. This novel class of chaperones undergoes massive unfolding by itself during unfolding conditions. But instead of becoming deactivated by these conditions as all other cellular proteins are, they became ACTIVE chaperones! They do not require ATP for their activity. The energy for their function is derived from structural conformational changes.  By combining computational biology with chaperone biochemistry and structural mass spectrometry, we are exploring the role of structural plasticity of these fascinating chaperones in their activity and interactions with other chaperones within the cell.  


Cell 2012; ARS 2017; Mol Cell 2018

Using structural mass spectrometry to understand the plasticity of protein-protein interactions



We are using and establishing cutting age technologies to identify, “catch” and validate protein-protein interactions in cells and in a tube. We love challenges, and therefore, we focus on conditionally disordered and aggregation-prone proteins which do not behave well in classical structural experiments (e.g., X-ray and NMR).

We utilize in-vivo and in-vitro crosslinking as well as hydrogen-deuterium exchange coupled with mass spectrometry to monitor structural plasticity and define binding interfaces. 





Cell 2012; JoVE 2018
Redox proteomics

Oxygen is one of the most important elements in life. Reactive oxygen species are continuously generated, transformed and consumed in all living organisms. High levels of reactive oxygen species can damage cells, and are associated with numerous diseases. Organisms have evolved complex systems to cope with high levels of oxygen, and use ROS to kill pathogens. At the same time, our cells use ROS for intracellular signaling processes that are transferred by specific redox-sensitive proteins, known as redox-switches.

In our lab, we use mass spectrometry-based techniques to quantify changes in the redox status of proteins. These techniques are used to map redox switches associated with different physiological functions, such as the circadian clock,  protein homeostasis, aging and others