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

James R.W. Conway; Sean C. Warren; Young Kyung Lee; Andrew T. McCulloch; Astrid Magenau; Victoria Lee; Xanthe L. Metcalf; Janett Stoehr; Katharina Haigh; Lea Abdulkhalek; Cristian S. Guaman; Daniel A. Reed; Kendelle J. Murphy; Brooke A. Pereira; Pauline Mélénec; Cecilia Chambers; Sharissa L. Latham; Helen Lenthall; Elissa K. Deenick; Yuanqing Ma; Tri Phan; Elgene Lim; Anthony M. Joshua; Stacey Walters; Shane T. Grey; Yan Chuan Shi; Lei Zhang; Herbert Herzog; David R. Croucher; Andy Philp; Colinda L.G.J. Scheele; David Herrmann; Owen J. Sansom; Jennifer P. Morton; Antonella Papa; Jody J. Haigh; Max Nobis; Paul Timpson

doi:10.1126/sciadv.adf9063

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

James R.W. Conway, Sean C. Warren, Young Kyung Lee, Andrew T. McCulloch, Astrid Magenau, Victoria Lee, Xanthe L. Metcalf, Janett Stoehr, Katharina Haigh, Lea Abdulkhalek, Cristian S. Guaman, Daniel A. Reed, Kendelle J. Murphy, Brooke A. Pereira, Pauline Mélénec, Cecilia Chambers, Sharissa L. Latham, Helen Lenthall, Elissa K. Deenick, Yuanqing MaTri Phan, Elgene Lim, Anthony M. Joshua, Stacey Walters, Shane T. Grey, Yan Chuan Shi, Lei Zhang, Herbert Herzog, David R. Croucher, Andy Philp, Colinda L.G.J. Scheele, David Herrmann, Owen J. Sansom, Jennifer P. Morton, Antonella Papa, Jody J. Haigh^*, Max Nobis^*, Paul Timpson^*

^*Tämän työn vastaava kirjoittaja

Turku Bioscience

Tutkimustuotos: Lehtiartikkeli › Artikkeli › Tieteellinen › vertaisarvioitu

1 Sitaatiot (Scopus)

4 Lataukset (Pure)

Abstrakti

Aberrant 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.

Alkuperäiskieli	Englanti
Artikkeli	eadf9063
Sivumäärä	15
Julkaisu	Science Advances
Vuosikerta	9
Numero	17
DOI - pysyväislinkit	https://doi.org/10.1126/sciadv.adf9063
Tila	Julkaistu - huhtik. 2023
OKM-julkaisutyyppi	A1 Julkaistu artikkeli, soviteltu

Pääsy asiakirjaan

10.1126/sciadv.adf9063

sciadv.adf9063Lopullinen julkaistu versio, 2,23 MBLisenssi: CC BY

https://urn.fi/URN:NBN:fi-fe202402136925

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Viittausmuodot

Conway, J. R. W., Warren, S. C., Lee, Y. K., McCulloch, A. T., Magenau, A., Lee, V., Metcalf, X. L., Stoehr, J., Haigh, K., Abdulkhalek, L., Guaman, C. S., Reed, D. A., Murphy, K. J., Pereira, B. A., Mélénec, P., Chambers, C., Latham, S. L., Lenthall, H., Deenick, E. K., ... Timpson, P. (2023). Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse. Science Advances, 9(17), Artikkeli eadf9063. https://doi.org/10.1126/sciadv.adf9063

@article{020e6061dc9b43bca011a781aeabc0bd,

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

abstract = "Aberrant 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.",

author = "Conway, {James R.W.} and Warren, {Sean C.} and Lee, {Young Kyung} and McCulloch, {Andrew T.} and Astrid Magenau and Victoria Lee and Metcalf, {Xanthe L.} and Janett Stoehr and Katharina Haigh and Lea Abdulkhalek and Guaman, {Cristian S.} and Reed, {Daniel A.} and Murphy, {Kendelle J.} and Pereira, {Brooke A.} and Pauline M{\'e}l{\'e}nec and Cecilia Chambers and Latham, {Sharissa L.} and Helen Lenthall and Deenick, {Elissa K.} and Yuanqing Ma and Tri Phan and Elgene Lim and Joshua, {Anthony M.} and Stacey Walters and Grey, {Shane T.} and Shi, {Yan Chuan} and Lei Zhang and Herbert Herzog and Croucher, {David R.} and Andy Philp and Scheele, {Colinda L.G.J.} and David Herrmann and Sansom, {Owen J.} and Morton, {Jennifer P.} and Antonella Papa and Haigh, {Jody J.} and Max Nobis and Paul Timpson",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors.",

year = "2023",

month = apr,

doi = "10.1126/sciadv.adf9063",

language = "English",

volume = "9",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American association for the advancement of science",

number = "17",

}

Conway, JRW, Warren, SC, Lee, YK, McCulloch, AT, Magenau, A, Lee, V, Metcalf, XL, Stoehr, J, Haigh, K, Abdulkhalek, L, Guaman, CS, Reed, DA, Murphy, KJ, Pereira, BA, Mélénec, P, Chambers, C, Latham, SL, Lenthall, H, Deenick, EK, Ma, Y, Phan, T, Lim, E, Joshua, AM, Walters, S, Grey, ST, Shi, YC, Zhang, L, Herzog, H, Croucher, DR, Philp, A, Scheele, CLGJ, Herrmann, D, Sansom, OJ, Morton, JP, Papa, A, Haigh, JJ, Nobis, M & Timpson, P 2023, 'Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse', Science Advances, Vuosikerta 9, Nro 17, eadf9063. https://doi.org/10.1126/sciadv.adf9063

TY - JOUR

T1 - Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse

AU - Conway, James R.W.

AU - Warren, Sean C.

AU - Lee, Young Kyung

AU - McCulloch, Andrew T.

AU - Magenau, Astrid

AU - Lee, Victoria

AU - Metcalf, Xanthe L.

AU - Stoehr, Janett

AU - Haigh, Katharina

AU - Abdulkhalek, Lea

AU - Guaman, Cristian S.

AU - Reed, Daniel A.

AU - Murphy, Kendelle J.

AU - Pereira, Brooke A.

AU - Mélénec, Pauline

AU - Chambers, Cecilia

AU - Latham, Sharissa L.

AU - Lenthall, Helen

AU - Deenick, Elissa K.

AU - Ma, Yuanqing

AU - Phan, Tri

AU - Lim, Elgene

AU - Joshua, Anthony M.

AU - Walters, Stacey

AU - Grey, Shane T.

AU - Shi, Yan Chuan

AU - Zhang, Lei

AU - Herzog, Herbert

AU - Croucher, David R.

AU - Philp, Andy

AU - Scheele, Colinda L.G.J.

AU - Herrmann, David

AU - Sansom, Owen J.

AU - Morton, Jennifer P.

AU - Papa, Antonella

AU - Haigh, Jody J.

AU - Nobis, Max

AU - Timpson, Paul

PY - 2023/4

Y1 - 2023/4

N2 - Aberrant 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.

AB - Aberrant 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.

UR - http://www.scopus.com/inward/record.url?scp=85158018642&partnerID=8YFLogxK

U2 - 10.1126/sciadv.adf9063

DO - 10.1126/sciadv.adf9063

M3 - Article

C2 - 37126544

AN - SCOPUS:85158018642

SN - 2375-2548

VL - 9

JO - Science Advances

JF - Science Advances

IS - 17

M1 - eadf9063

ER -

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

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