European Commission logo
English English
CORDIS - EU research results
CORDIS

Regulation of Processing Body Composition, Function and Fate during Different Stresses at Endoplasmic Reticulum-Membrane Contact Sites

Project description

Regulation of the processing bodies’ composition, dynamics and turnover under stress

Eukaryotic cellular stress results in the formation of cytoplasmic stress granules and processing bodies (PBs). The membraneless PB granules vary in their dynamic of the assembly/disassembly and composition depending on the type of stress. Funded by the Marie Skłodowska-Curie Actions programme, the PBStressERMCSs project proposes to study the content, dynamics and turnover of PBs under endoplasmic reticulum and mitochondrial/lysosomal stresses, induced by pharmacological and acute genetic interventions. The study will use purified PBs and employ liquid chromatography-mass spectrometry analysis for proteins and RNA-sequencing for the RNA content to identify the signals affecting PB localisation, development and conservation of PB stress response in mammalian cells.

Objective

One of the first responses to eukaryotic cellular stress is the formation of cytoplasmic granules like processing bodies (PBs) and stress granules (SGs). PBs are membrane-less structures that are dynamic in their assembly/disassembly and composition depending on the type of stress that they encounter. While glucose starvation is the main stress applied to study PB formation and dynamics, much less is known about PBs under other stresses, especially endoplasmic reticulum (ER) and mitochondrial/lysosomal stresses. We propose to study the formation, content and dynamics of PBs under ER and mitochondrial/lysosomal stresses, together with their turnover (autophagy/dissolution) during stress recovery. I plan to use pharmacological and acute genetic interventions to induce stresses. PBs will be purified according to the established protocol in the laboratory, which enables subsequent Liquid chromatography-mass spectrometry (LC-MS) analysis for proteins and RNA-sequencing for the RNA content. Probing stress response further, we will also perform total RNA-sequencing and Ribosome-profiling. The fate of specific sets of mRNAs will be determined by FISH-IF and RNA decay analysis, thereby identifying the signals effectuating PB localization and fate (storage or decay) during ER and mitochondrial/lysosomal stress. The study will be extended to check conservation of PB stress response in mammalian cells. The proposed research will provide a holistic view on the pathways that are up- or down-regulated during ER and mitochondrial/lysosomal stress, the identification of common pathways between the different stresses and PB -mRNA and protein- turnover. This project will be of high impact in the fields of cancer, cell, and neuro biology.

Coordinator

UNIVERSITAT BASEL
Net EU contribution
€ 191 149,44
Address
PETERSPLATZ 1
4051 Basel
Switzerland

See on map

Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 191 149,44