New biology of oncogenic PI 3-kinase

Informazioni relative al progetto

Oncogenic PI3-kinase

ID dell’accordo di sovvenzione: 838559

DOI

10.3030/838559

Progetto chiuso

Data della firma CE 19 Marzo 2019

Data di avvio 1 Maggio 2019

Data di completamento 30 Aprile 2021

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 212 933,76

Contributo UE

€ 212 933,76

Coordinato da

UNIVERSITY COLLEGE LONDON
United Kingdom

Periodic Reporting for period 1 - Oncogenic PI3-kinase (New biology of oncogenic PI 3-kinase)

Periodo di rendicontazione: 2019-05-01 al 2021-04-30

Sintesi del contesto e degli obiettivi generali del progetto

This project studied PI 3-kinases (PI3Ks in short) that regulate fundamental processes in cells. Inhibitors against PI3K family members are now approved for the treatment of leukaemia and breast cancer. We focused on a PI3K family member which has been implicated in disease, including in cancer. Despite extensive research, key elements of PI3K biology are poorly understood, in part because we believe PI3K function has not been investigated in the appropriate conditions and models.
The primary cilium is a much-overlooked structure in a cell. This is a small antenna-like structure that projects out of each cell to sense the environment and is important for development and normal adult cell function. Here we have studied a new function for PI3K in controlling the primary cilium biology and identified novel signalling downstream of PI3K signalling.
We believe our findings have the potential to uncover insights into long-standing questions the in cilia biology field and help to understand how increased activity of PI3K contributes to disease. Understanding the mechanistic basis of disease informs and is essential for the process of drug development.

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

We have established multiple techniques in the laboratory to increase and reduce PI3K activity in mice and cells. We have characterised the effects of increased PI3K activity in the developing mouse embryo. Furthermore, we have performed a comprehensive characterisation of the effects of altered PI3K activity on cilia biology in cells using both targeted and unbiased approaches.

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)

This project has identified a new role for PI3K in regulation of primary cilia biology. Primary cilia dysfunction is an important cause of human disease. Understanding how PI3K controls primary cilia will provide critical insight into diseases caused by both mutations in PI3K and abnormal cilia function and may inform future drug development efforts.

cilia phosphoinositides