Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse

Simple item page
dc.contributor.authorConway, J.R.W.
dc.contributor.authorWarren, S.C.
dc.contributor.authorLee, Y.-K.
dc.contributor.authorMcCulloch, A.T.
dc.contributor.authorMagenau, A.
dc.contributor.authorLee, V.
dc.contributor.authorMetcalf, X.L.
dc.contributor.authorStoehr, J.
dc.contributor.authorHaigh, K.
dc.contributor.authorAbdulkhalek, L.
dc.contributor.authorGuaman, C.S.
dc.contributor.authorReed, D.A.
dc.contributor.authorMurphy, K.J.
dc.contributor.authorPereira, B.A.
dc.contributor.authorMélénec, P.
dc.contributor.authorChambers, C.
dc.contributor.authorLatham, S.L.
dc.contributor.authorLenthall, H.
dc.contributor.authorDeenick, E.K.
dc.contributor.authorMa, Y.
dc.contributor.authoret al.
dc.date.issued2023
dc.description.abstractAberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.
dc.description.statementofresponsibilityJames R. W. Conway ... Antonella Papa ... et al.
dc.identifier.citationScience Advances, 2023; 9(17):eadf9063-1-eadf9063-15
dc.identifier.doi10.1126/sciadv.adf9063
dc.identifier.issn2375-2548
dc.identifier.issn2375-2548
dc.identifier.orcidPapa, A. [0000-0001-8653-7121]
dc.identifier.urihttps://hdl.handle.net/2440/146208
dc.language.isoen
dc.publisherAmerican Association for the Advancement of Science
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1155678
dc.relation.grantARC
dc.rightsCopyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
dc.source.urihttps://doi.org/10.1126/sciadv.adf9063
dc.subjectAkt-FRET biosensor mouse; cancer
dc.subject.meshAnimals
dc.subject.meshMice
dc.subject.meshFluorescence Resonance Energy Transfer
dc.subject.meshBiosensing Techniques
dc.subject.meshProto-Oncogene Proteins c-akt
dc.titleMonitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse
dc.typeJournal article
pubs.publication-statusPublished online

Files

Collections

Research Outputs