Academy of Finland  
Funding decision
Organisation University of Helsinki
Project title Chemical biology approach for dissecting ER proteostasis
Applicant / Contact person Paavilainen, Ville
Decision No. 338836
Decision date 03.06.2021
Funding period 01.09.2021 - 31.08.2025
Funding 598 642
Project description
The ability to maintain localized proteomes is essential for correct physiology and ability of cells to carry out otherwise incompatible chemistries. One key proteostasis hub is the endoplasmic reticulum, which coordinates the biogenesis, folding and quality control of a large fraction of the proteome of eukaryotic cells. Most of the protein homeostasis pathways require transient adaptations, which cannot be studied by conventional genetic methods. Instead small molecule chemical probes are required for investigations with high temporal precision. This project uses new natural or nature-inspired chemical probes to study coordination of essential polypeptide processing steps within the ER and to reveal new mechanisms underlying the cells’ ability to adapt to accumulation of misfolded proteins within the ER lumen. Collectively, the project aims to identify new therapeutic targets and privileged chemical scaffolds for future development of therapies against protein misfolding diseases.