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H2020Individual fellowship2021–2023

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

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2021-08-01 → 2023-07-31
EU contribution
€191,149
Participants
1
Scheme
MSCA-IF

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Results in brief

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

There is still very little knowledge in literature about what exactly happens when a cell responds to stress. We and others have observed the formation of certain "stress specific granules"which are called P bodies that could store certain proteins and RNA till the time the stress is removed or the cell gets stress adapted. We have tried to characterise the composition, function and fate of these P bodies in general across different stresses. In this context we have chosen stresses that the cell could face on a day to day basis so that our work can eventually translate into something physiological that would unravel mechanisms behind these cellular stresses and also enlighten us on the molecular players that play a potential role behind the stress-sensing. This project is very important for society because a detailed in-depth study on cellular stress has not been undertaken very well. The project is of high impact not only for the RNA and translational control fields but more generally for the fields of cancer, cell and neurobiology. The over-arching aim/objective of the project is to holistically study the life-cycle of PBs under the different stresses----tracking their formation, localisation in the cell, studying their composition, function and fate.

Data: CORDIS, © European Union

Project 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.

Original text from CORDIS.

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Data: CORDIS, © European Union