Reference : UMR9198-FREFRO-001
Workplace : GIF SUR YVETTE
Date of publication : Tuesday, September 13, 2022
Scientific Responsible name : FROTTIN Frédéric
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 March 2023
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Background: Proteostasis (or protein homeostasis) is essential and its collapse is associated with numerous diseases. The generation of misfolded proteins and aggregates is the hallmark of many neurodegenerative disorders, cancers, and aging. Thus, cells have evolved a protein quality control network of components that act to maintain and restore proteostasis. The nucleus is a target of pathological aggregation but pathways that handle nuclear misfolded proteins are not well understood. Recently, it has been discovered that an integral part of the cellular management of nuclear misfolded proteins is their reversible sequestration into the nucleolus upon proteotoxic stress. Therefore, the nucleolus prevents irreversible and toxic protein aggregation highlighting a novel chaperone-like function. The nucleolus is a paradigm example of liquid-like phase separated compartment that is formed through multivalent interactions of its constituents. The liquid-like nature of the organelle ensures its protein quality control function. How this is regulated is largely elusive as well as the factors required for nucleolar translocation of misfolded proteins.
Aim of the project: To discover new players involved in the regulation of the nucleolar protein quality control pathway. In particular, the project aims to decipher the impact of protein modifications, such as lysine acetylation, on nuclear protein quality control and biocondensate properties.
To this end, the student will take advantage of the excellent scientific environment of the I2BC and CNRS campus. This integrative study will make use of cellular biochemistry, quantitative proteomics, fixed and live-cell imaging, optogenetic tools, and cell-free systems. The student will have access (within the building) to the imaging facility and mass spectrometry facility that are running state-of-the-art instruments. The student will benefit from the recognized expertise of the team in in vitro analysis, microscopy, and mass spectrometry with privileged access to these equipment.
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