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

Project Information

PBStressERMCSs

Grant agreement ID: 101030442

DOI

10.3030/101030442

Project closed

EC signature date 8 July 2021

Start date 1 August 2021

End date 31 July 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 191 149,44

EU contribution

€ 191 149,44

Coordinated by

UNIVERSITAT BASEL
Switzerland

Periodic Reporting for period 1 - PBStressERMCSs (Regulation of Processing Body Composition, Function and Fate during Different Stresses at Endoplasmic Reticulum-Membrane Contact Sites)

Reporting period: 2021-08-01 to 2023-07-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

As written in detail in the technical report, we could show that PBs do form under the different stresses that we have studied.

We were able to identify that under different stresses their numbers and morphologies are different.
We were also able to characterise that they are mostly liquid-liquid phase separated condensates having proteins and RNA which could change over time (acute stress of 10 min and prolonged stress of 60 min)
Our high-throughput data on proteomics and RNA-seq gave us a list of molecular players and pathways which we are currently validating.

Our findings which are in yeast system could be extended to mammalian systems where these novel proteins could serve as molecular markers of prognosis and lead to the discovery of new potential drugs to restore drug sensitivity or other therapeutic interventions.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The progress of the project has been very satisfactory and we are currently in the process of writing a manuscript for the first part where we talk about the PBs and discuss their characterisation under the different stresses.

The great academic environment at the BZ has been very rewarding including the scientific feedback from other scientists, the help from the individual facilities have been very good.

It has definitely enhanced my future career prospects after the fellowship as well as if I were to look for a scientific career after my postdoctoral tenure.

As I believe the findings when extended to mammalian cellular systems could benefit the scientific community in specific and the society as well because there is very less knowledge about how stress translates to neurological disorders, cancer progression and induces chemotherapy resistance.

The project has opened new pathways of research for future masters students and graduate students in the lab and my outreach activities and scientific communication in seminars, conferences, open-house days have been very well appreciated by the audience (both scientific and in general)

Declaration that the project does not yet have a publication