Aitana Victoria Genzor Garbayo

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A key process in cell survival and homeostasis is the transduction of environmental signals into adaptation responses. In this context, the MAP kinase pathways are major signal cascades. Activated by cytokines, hormones and diverse stresses, MAP kinase cascades coordinate distinct aspects of cellular physiology, including cell growth and apoptosis. Knowledge of these pathways is relevant for human health as it can give valuable insight into how cells can cope in disease-like environments, were many of these environmental cues are present.

The overall focus of my PhD is to study the physiological relevance of the MAP kinase stress signaling pathways. In particular, our group is interested in the role of MAP3 kinase ZAK in the cell. ZAK mediates MAPK activation in response to a diversity of stresses including UV irradiation, osmotic and ribotoxic stress. Interestingly, we have shown that starvation also activates this kinase. Part of my investigation aims to decipher the molecular mechanisms behind this process. ZAK activation under nutrient deprivation depends on its ability to bind to ribosomes. Moreover, compelling data indicates that translation stress caused by depletion of amino acids triggers ZAK activation and dissociation from ribosomes. In my project, I also explore possible interplays with other master regulators of cell metabolism such as mTOR, AMPK and GCN2. For this purpose, I rely on powerful genetic tools available in C.elegans and Danio rerio, two well-characterized model organisms. Results from C.elegans already indicate a strong interaction between ZAK and GCN2 kinases not only under starvation but also under other stresses. In these conditions, ZAK exerts a protective role that influences organism survival and lifespan, highlighting the physiological importance of this kinase at the organism level.