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Barry James Thompson

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Barry James Thompson
Born1978 (age 45–46)
Darwin, Australia
NationalityAustralian, British
Alma materUniversity of Queensland (UQ), University of Cambridge
AwardsLMB Max Perutz Prize (2003), EMBO Young Investigator Award (2012), Wellcome Trust Investigator Award (2014), EMBL Australia Fellowship (2019).
Scientific career
FieldsDevelopmental biology, Epithelial polarity, Hippo signaling pathway
Institutions
Thesis The Drosophila gene pygopus encodes a new nuclear component of the Wingless signalling pathway  (2004)
Doctoral advisorMariann Bienz
Other academic advisorsStephen M Cohen, Barry Dickson
Websitewww.emblaustralia.org/about/our-people/barry-thompson

Barry James Thompson (born 1978) is an Australian and British developmental biologist and cancer biologist. Thompson is known for identifying genes, proteins and mechanisms involved in epithelial polarity, morphogenesis and cell signaling via the Wnt and Hippo signaling pathways, which have key roles in human cancer.

Early life and education

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Barry Thompson was born in 1978 into a British-Australian family. He was raised on the Atherton Tableland and in Brisbane in the state of Queensland (Australia). He attended Atherton State Primary School and Brisbane State High School and graduated as school Dux in 1995.[1]

Scientific career

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Thompson became interested in developmental biology and the control of tissue growth in 2000 when studying BSc(Hons) at the University of Queensland's Institute for Molecular Biology (IMB) with Professor Michael Waters.[2]

He earned his PhD degree at the MRC Laboratory of Molecular Biology and University of Cambridge (United Kingdom), where he studied the Wnt signaling pathway in Drosophila melanogaster with Dr Mariann Bienz.[3][4]

He then moved to Germany to work at the European Molecular Biology Laboratory with Prof Stephen M Cohen. There he studied the role of the Hippo signaling pathway during Drosophila development.[5]

In 2007, Thompson was a visiting scientist at the Research Institute of Molecular Pathology in Vienna (Austria), where he worked in the laboratory of Dr Barry Dickson to perform a genome-wide in vivo RNAi screen in Drosophila. In 2008, Thompson established his own laboratory at the Cancer Research UK London Research Institute, which became part of the Francis Crick Institute in 2015. In 2019, Thompson was appointed Professor at the John Curtin School of Medical Research at the Australian National University. His service was terminated in October 2023 due to his actions of sexual harassment.[6]

Research areas

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Epithelial cell polarity

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His laboratory works on the molecular mechanisms of epithelial polarity, including both apical-basal polarity and planar cell polarity, using Drosophila melanogaster epithelial tissues as an experimental model system. His laboratory discovered that apical-basal polarisation of the transmembrane protein Crumbs - a key apical determinant - depends upon both a Cdc42-driven positive feedback loop as well as mutual antagonism between apical and basolateral determinants.[7][8] The Cdc42-driven positive feedback loop involves recruitment of Cdc42 complexes by Crumbs, followed by Cdc42-mediated polarisation of the cytoskeleton, including both actin filaments and microtubules, that allow transport of Crumbs-containing vesicles by the microtubule motor protein Dynein and the actin motor protein Myosin-V.[9][10] How Cdc42 polarises the cytoskeleton remains an important unsolved problem, but Cdc42 appears to act primarily via activating the kinases aPKC and Pak1 in Drosophila follicle cells.[11]

His laboratory also discovered that planar cell polarisation of the atypical myosin Dachs by the Fat and Dachsous cadherins is responsible for polarising tension at adherens junctions and thus influencing the orientation of cell shapes and cell divisions within the plane of the epithelium.[12] His lab subsequently found that this involved recruitment of the ubiquitin ligase FbxL7 to Fat, in order to degrade Dachs on one side of the cell, such that Dachs binds to Dachsous on the opposite side of the cell.[13]

Epithelial cell division and spindle orientation

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Thompson's laboratory found that cell divisions in epithelia can also be oriented by mechanical forces arising from adjacent tissues growing at different rates.[14] In order for the mitotic spindle to orient in response to planar forces, highly columnar pseudostratified epithelial cells must round up at mitosis in a process that involves the Aurora A and B kinases, activation of Rho-mediated actomyosin contractility, remodelling of adherens junctions, and removal of the Lgl protein from the plasma membrane to allow spindle orienting factors to interact with Dlg/Scrib proteins and thereby align the spindle within the plane of the epithelium.[15][16]

Epithelial morphogenesis

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While epithelial cell polarity and cell proliferation are fundamental to the construction of an epithelium, and can influence the form of the entire tissue, epithelial morphogenesis also depends fundamentally on anchorage to the extracellular matrix (ECM). Thompson's lab showed that synthesis and enzymatic remodelling of the ECM were crucial to the shaping of Drosophila melanogaster tissues, particularly for formation of the adult fly wings, legs and halteres during metamorphosis.[17][18][19]

Hippo signaling

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Thompson's lab discovered several components of the Hippo signaling pathway in Drosophila melanogaster (including Kibra,[20] Spectrins,[21] Mask[22]) and that this pathway functions to sense mechanical strain during development of epithelial cells in vivo,[23] as well as to sense nutritional status via the hormonal Insulin/IGF-1 and PI3K-Akt pathway,[24] in order to control cell proliferation, cellular morphology, and invasive cell migration. His lab has also had a major interest in the role of the Hippo pathway in mammals, including humans, where (unlike Drosophila) the pathway also responds to input from Integrin-Src family kinase signals to enable the mechanical control of epithelial cell proliferation and tissue regeneration, .[25][26]

References

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  1. ^ "Past Dux of School". 21 November 2019.
  2. ^ Thompson, Barry; Shang, Catherine; Waters, Michael (2000). "Identification of genes induced by growth hormone in rat liver using cDNA arrays". Endocrinology. 141 (11): 4321–4324. doi:10.1210/endo.141.11.7874. PMID 11089569.
  3. ^ Thompson, Barry; Townsley, Fiona; Rosin, Rina; Musisi, Hannah; Bienz, Mariann (2002). "A new nuclear component of the Wnt signalling pathway". Nature Cell Biology. 4 (5): 367–73. doi:10.1038/ncb786. PMID 11988739. S2CID 23942463.
  4. ^ Thompson, Barry (2004). "A Complex of Armadillo, Legless, and Pygopus Coactivates dTCF to Activate Wingless Target Genes". Current Biology. 14 (6): 1–20. doi:10.1016/j.cub.2004.02.026. PMID 15043810. S2CID 6121751.
  5. ^ Thompson, B.; Cohen, S.M. (2006). "The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila". Cell. 126 (4): 767–74. doi:10.1016/j.cell.2006.07.013. PMID 16923395. S2CID 15264514.
  6. ^ DeadestLift (15 May 2022). "Heads up for women who shop at Dickson - harassment and unwanted attention". r/canberra. Retrieved 22 May 2024.
  7. ^ Fletcher, G.C.; Lucas, E.P.; Brain, R.; Tournier, A.; Thompson, B.J. (2012). "Positive feedback and mutual antagonism combine to polarize Crumbs in the Drosophila follicle cell epithelium". Current Biology. 22 (12): 1116–1122. doi:10.1016/j.cub.2012.04.020. PMID 22658591. S2CID 16648144.
  8. ^ Thompson, B.J. (2013). "Cell polarity: models and mechanisms from yeast, worms and flies". Development. 140 (1): 13–21. doi:10.1242/dev.083634. PMID 23222437. S2CID 7117523.
  9. ^ Khanal, I.; Elbediwy, A.; Diaz de la Loza, M.C.; Fletcher, G.C.; Thompson, B.J. (2016). "Shot and Patronin polarise microtubules to direct membrane traffic and biogenesis of microvilli in epithelia". Journal of Cell Science. 129 (13): 2651–2659. doi:10.1242/jcs.189076. PMC 4958304. PMID 27231092.
  10. ^ Aguilar-Aragon, M.; Fletcher, G.; Thompson, B.J. (2020). "The cytoskeletal motor proteins Dynein and MyoV direct apical transport of Crumbs". Developmental Biology. 459 (2): 126–137. doi:10.1016/j.ydbio.2019.12.009. PMC 7090908. PMID 31881198.
  11. ^ Aguilar-Aragon, M.; Elbediwy, A.; Foglizzo, V.; Fletcher, G.C.; Li, V.S.W; Thompson, B.J. (2018). "Pak1 Kinase Maintains Apical Membrane Identity in Epithelia". Cell Reports. 22 (7): 1639–1646. doi:10.1016/j.celrep.2018.01.060. PMC 5847184. PMID 29444419.
  12. ^ Mao, Y.; Tournier, A.; Bates, P.; Gale, J.E.; Tapon, N.; Thompson, B.J. (2011). "Planar polarization of the atypical myosin Dachs orients cell divisions in Drosophila". Genes & Development. 25 (2): 131–136. doi:10.1101/gad.610511. PMC 3022259. PMID 21245166.
  13. ^ Rodrigues-Campos, M.; Thompson, B.J. (2014). "The ubiquitin ligase FbxL7 regulates the Dachsous-Fat-Dachs system in Drosophila". Development. 141 (21): 4098–4103. doi:10.1242/dev.113498. PMC 4302899. PMID 25256343.
  14. ^ Mao, Y.; Tournier, A.; Hoppe, A.; Kester, L.; Thompson, B.J.; Tapon, N. (2013). "Differential proliferation rates generate patterns of mechanical tension that orient tissue growth". EMBO Journal. 32 (21): 2790–2803. doi:10.1038/emboj.2013.197. PMC 3817460. PMID 24022370.
  15. ^ Bell, G.P.; Fletcher, G.C.; Brain, R.; Thompson, B.J (2015). "Aurora kinases phosphorylate Lgl to induce mitotic spindle orientation in Drosophila epithelia". Current Biology. 25 (1): 61–68. doi:10.1016/j.cub.2014.10.052. PMC 4291145. PMID 25484300.
  16. ^ Aguilar-Aragon, M.; Bonello, T.T.; Bell, G.P.; Fletcher, G.C; Thompson, B.J. (2015). "Adherens junction remodeling during mitotic rounding of pseudostratified epithelial cells". Current Biology. 25 (1): 61–68. doi:10.1016/j.cub.2014.10.052. PMC 4291145. PMID 25484300. S2CID 13953651.
  17. ^ Ray, R.P.; Matamoro-Vidal, A.; Ribeiro, P.S.; Tapon, N; Houle, D.; Salaar-Cuidad, I.; Thompson, B.J. (2015). "Patterned Anchorage to the Apical Extracellular Matrix Defines Tissue Shape in the Developing Appendages of Drosophila". Developmental Cell. 34 (3): 310–22. doi:10.1016/j.devcel.2015.06.019. PMC 4539345. PMID 26190146.
  18. ^ Diaz de la Loza, M.D.; Ray, R.P.; Ganguly, P.S.; Alt, S.; Davis, J.R.; Hoppe, A.; Tapon, N.; Thompson, B.J. (2018). "Apical and Basal Matrix Remodeling Control Epithelial Morphogenesis". Developmental Cell. 46 (1): 23–39. doi:10.1016/j.devcel.2018.06.006. PMC 6035286. PMID 29974861.
  19. ^ Diaz de la Loza, M.D.; Loker, R.; Mann, R.S.; Thompson, B.J. (2020). "Control of tissue morphogenesis by the HOX gene Ultrabithorax". Development. 147 (5): 23–39. doi:10.1016/j.devcel.2018.06.006. PMC 6035286. PMID 29974861. S2CID 49656207.
  20. ^ Genevet, A.; Wehr, M.C.; Brain, R.; Thompson, B.J.; Tapon, N. (2010). "Kibra is a regulator of the Salvador/Warts/Hippo signaling network". Developmental Cell. 18 (2): 300–308. doi:10.1016/j.devcel.2009.12.011. PMC 2845807. PMID 20159599.
  21. ^ Fletcher, G.C.; Elbediwy, A.; Khanal, I.; Ribeiro, P.S.; Tapon, N.; Thompson, B.J. (2010). "The Spectrin cytoskeleton regulates the Hippo signalling pathway". Developmental Cell. 18 (2): 300–308. doi:10.1016/j.devcel.2009.12.011. PMC 2845807. PMID 20159599. S2CID 25838419.
  22. ^ Sidor, C.M.; Brain, R.; Thompson, B.J. (2013). "Mask proteins are cofactors of Yorkie/YAP in the Hippo pathway". Current Biology. 23 (3): 223–228. doi:10.1016/j.cub.2012.11.061. PMID 23333315. S2CID 16722199.
  23. ^ Fletcher, G.C.; Diaz-de-la-Loza, M.D.; Borreguero-Munoz, N.; Holder, M.; Aguilar-Aragon, M.; Thompson, B.J. (2018). "Mechanical strain regulates the Hippo pathway in Drosophila". Development. 145 (5): dev159467. doi:10.1242/dev.159467. PMC 5868995. PMID 29440303.
  24. ^ Borreguero-Munoz, N.; Fletcher, G.C.; Aguilar-Aragon, M.; Elbediwy, A.; Vincent-Mistiaen, Z.I.; Thompson, B.J. (2019). "The Hippo pathway integrates PI3K-Akt signals with mechanical and polarity cues to control tissue growth". PLOS Biology. 17 (10): e3000509. doi:10.1371/journal.pbio.3000509. PMC 6814241. PMID 31613895.
  25. ^ Elbwediwy, A.; Vincent-Mistiaen, Z.I.; et, al; Thompson, B.J. (2016). "Integrin signalling regulates YAP and TAZ to control skin homeostasis". Development. 143 (10): 1674–1687. doi:10.1242/dev.133728. PMC 4874484. PMID 26989177.
  26. ^ Elbediwy, A.; Thompson, B.J. (2018). "Evolution of mechanotransduction via YAP/TAZ in animal epithelia". Current Opinion in Cell Biology. 51: 117–123. doi:10.1016/j.ceb.2018.02.003. PMID 29477107.
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