Periodic Reporting for period 1 - Oncogenic PI3-kinase (New biology of oncogenic PI 3-kinase)
Reporting period: 2019-05-01 to 2021-04-30
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.
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.
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.
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.