Nencki Institute Seminar

Dear All

On behalf of prof. Grzegorz Sumara, I would like to cordially invite you to the next Nencki Institute Seminar which will take place next Thursday, September 28th at 3pm in the CN lecture hall. We will host prof. Simon Bekker-Jensen, who is a group leader at the Department of Cellular and Molecular Medicine at the University of Copenhagen in Denmark.

Prof. Bekker-Jensen investigates the molecular mechanisms of cell’s response to stress and how the pathways that allow the cell to react and accommodate to challenging environment are rewired in aging and in diseases such as cancer. The findings of his research group have recently been published in Nature Cell Biology, Cell Metabolism or EMBO J. He received numerous grants and awards including an ERC starting grant.

 Prof. Bekker-Jensen will give a talk entitled: Ribosomes as sensors of exposure to free radicals, radiation and toxic metabolites. 


The ribotoxic stress response (RSR) denotes a signaling pathway in which the MAP3 kinase ZAKa senses ribosomal stalling and/or collision to activate the MAP kinases p38 and JNK. These kinases in turn mediate metabolic regulation, programmed cell death and inflammation, just to mention a few. The evolutionary conservation of the response is well-appreciated and some insight into the molecular underpinnings have been gleaned. However, we know preciously little about the physiological and pathological conditions that are associated with ribotoxic stress signaling in vivo.

Our recent work with ZAK-/- mice highlights ribosomes as exquisitely sensitive sensors of a range of stress conditions, and the RSR as an effector pathway for stress adaptation at a tissue-wide and/or organismal level. I will discuss our unpublished work highlighting the role of RSR signaling in metabolic adaptation to amino acid starvation and ROS-generating diets. I will also describe the emerging role of the RSR in skin reactions to UV-irradiation (sun exposure), where ZAKa, p38 and JNK orchestrate early pyroptosis, apoptosis and immune cell infiltration.

Finally, I will discuss the role of the RSR in the clinically relevant reaction to paracetamol overdose which is associated with depletion of hepatocyte glutathione content, oncotic necrosis and fulminant liver failure. I will show how the paracetamol metabolite “NAPQI” is a potent ribotoxic stress inducer on account of its reaction with ribosomal and messenger RNA. In this context, the RSR mediates early and protective apoptotic cell death that soon gives way to uncontrolled and JNK-independent necrosis.

In sum, our work highlights free radicals, UV radiation and toxic metabolites as physiologically and/or pathologically relevant ribotoxic stress agents.

The seminar will be followed by a get together.

With kind regards

Aleksandra Pękowska

22 September 2023
2023-09-28 15:00:00
2023-09-28 16:30:00
Nencki Institute