Coincidence detection of proteins and lipids in regulation of cellular membrane dynamics

Informazioni relative al progetto

CODE

ID dell’accordo di sovvenzione: 788954

DOI

10.3030/788954

Progetto chiuso

Data della firma CE 31 Maggio 2018

Data di avvio 1 Gennaio 2019

Data di completamento 31 Dicembre 2024

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 2 500 000,00

Contributo UE

€ 2 500 000,00

Coordinato da

UNIVERSITETET I OSLO
Norway

Periodic Reporting for period 4 - CODE (Coincidence detection of proteins and lipids in regulation of cellular membrane dynamics)

Periodo di rendicontazione: 2023-07-01 al 2024-12-31

Sintesi del contesto e degli obiettivi generali del progetto

An overarching principle in the biology of eukaryotic cells is that distinct proteins and lipids localise to distinct cellular membranes to perform compartment‐specific functions. A long‐standing question has been how such specific localisation is achieved. In the CODE project we have investigated the hypothesis that coincidence detection of proteins and lipids is a major mechanism to achieve specificity in cytosol‐to-membrane recruitment of proteins and their complexes.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

We have used mathematical modelling to model molecular kinetics of coincidence detection and predicted the relationship between coincidence detection and protein localisation, and we have investigated coincidence detection of the membrane lipid phosphatidylinositol 3‐phosphate (PI3P) and various proteins as a paradigm for how coincidence detection controls protein localisation, membrane contact site formation, and membrane dynamics. We have screened for new coincidence detectors using bioinformatics, quantitative proteomics and molecular biology approaches. These coincidence detectors have been functionally characterized in cell culture and model organisms and found to control cancer cell invasion, cancer cell nutrition, genome stability and other biologically relevant mechanisms. Their pharmacological inhibition might offer new therapeutic strategies in cancer. Results have been presented at international scientific conferences and leading scientific journals (including Nature Cell Biology, Cell Research, Nature Communications and EMBO Journal) and have been popularized online on web pages, social media and in popular-scientific magazines.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

We have proven that coincidence detection is an important principle in recruitment of proteins to biological membranes, and that it plays a major role in diverse cellular processes, including cancer cell invasion, cancer cell nutrition, and maintenance of genome stability.

The coincidence detector WDFY2 i present on endosome tubules. Stills from a movie