Cellular modelling of Type IA PI3K dynamics in health and disease

Research output: Contribution to journalMeeting abstractpeer-review


Mosaic activating mutations in PIK3CA, the gene encoding the catalytic p110a subunit of class IA phosphoinositide 3-kinase (PI3K), are frequently found in patients with severe early-onset segmental overgrowth. Whilst differences in timing and location of the founder mutation are likely to explain part of the observed disease heterogeneity, it is less clear whether and how quantitative differences in the strength and timing of PI3K activity contribute to phenotypic variability.

Our aim is to characterise PIK3CA mutant-specific signalling as well as to explore the effects of varying the strength and/or temporal pattern of PI3K activation on downstream output specificity in the cell. We are currently employing CRISPR/Cas9-mediated gene editing in human induced pluripotent stem cells to generate isogenic disease models of three such activating PIK3CA mutations. These cells will be used for signalome profiling by reverse-phase protein arrays (RPPA) to compare and contrast mutant-dependent alterations to candidate signalling networks.In parallel, ongoing efforts focus on developing an endogenously expressed optogenetic p110a, allowing precise spatiotemporal control over PI3K signaling to unravel the extent to which PI3K-dependent phenotypes are determined by strength of activation and/or dynamic encoding.

Ultimately, the outcome of this research will yield novel insight into fundamental aspects of PI3K signalling and potentially aid the development of targeted therapies for human diseases of PI3K hyperactivation.
Original languageEnglish
Pages (from-to)299-300
Number of pages2
JournalFEBS Journal
Issue numberSuppl. 1
Publication statusPublished - 7 Sept 2016
Event41st FEBS Congress: Molecular and Systems Biology for a Better Life - Kuşadası, Turkey
Duration: 3 Sept 20238 Sept 2023


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