PI(3,4,5)P3 signalling in epithelial cells

Class I PI3K signalling is one of the most important signalling networks in mammalian cells and is under intense investigation by the pharmaceutical sector. However, many of the underlying principles by which it operates are still unknown, thereby limiting our understanding of many aspects of biology, such as cell migration and growth, and hindering drug development.

A central issue is that a range of technological challenges have prevented an adequate, quantitative dissection of factors governing how the central signal in the system, PI(3,4,5)P3, is produced, activates its effectors and is degraded. We propose to tackle this problem by applying a combination of novel lipidomics, modern cell biology and modelling methods to understand the key factors that shape PI(3,4,5)P3 signalling in response to hormones and oncogenic mutation in a non-transformed, human, breast epithelial cell line.

Using Next Generation Sequencing technology we are studying the role of PI(3,4,5)P3 signalling in the regulation of genes expression levels upon hormonal stimulation in MCF10a cells. We are also analysing the adaptation/changes induced by presence of oncogenic mutations and that could influence the fate of the cell toward transformation.