Anne Bertolotti Explained

Anne Bertolotti
Fields:BiochemistryCell BiologyNeuroscience
Workplaces:IGBMCSkirball Institute of Biomolecular Medicine in the New York University School of MedicineEcole Normale Superieure, Paris FranceInsermMRC Laboratory of Molecular Biology
Alma Mater:University of Strasbourg, France
Thesis1 Title:and
Thesis2 Title:)-->
Thesis1 Url:and
Thesis2 Url:)-->
Thesis1 Year:and
Thesis2 Year:)-->
Doctoral Advisors:)-->
Awards:EMBO Young Investigator (2004)EMBO member (2013)British Society for Cell Biology Hooke Medal (2014)Fellow of the UK Academy of Medical Sciences (2017)Biochemical Society GlaxoSmithKline Award (2017)
Website:https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/anne-bertolotti/

Anne Bertolotti is a French biochemist and cell biologist who works as Programme Leader at the MRC Laboratory of Molecular Biology (MRC LMB) in Cambridge, UK.[1] In 2022 she was appointed Head of the MRC LMB's Neurobiology Division.[2] She is known for her research into the cellular defences against misfolded proteins and the mechanisms underlying their deposition, the molecular problem causative of neurodegenerative diseases.[3]

Education

Anne Bertolotti earned 2 B.S. degrees in biochemistry and plant physiology and an M.S. degree in cell and molecular biology from the Louis Pasteur University of Strasbourg, France. Bertolotti also received her PhD from the Louis Pasteur University for the discovery of hTAFII68 (now TAF15) while working with Laszlo Tora and Pierre Chambon at Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC).

Academic career

Bertolotti did her post-doctoral research with David Ron at the Skirball Institute of Biomolecular Medicine, NYU Medical Center, New York, United States, making seminal discoveries in the mammalian unfolded protein response.[4] [5] [6]

In 2001, Bertolotti became an Inserm Associate Professor at Ecole Normale Superieure, Paris.[7] In 2006, she became a group leader at the MRC Laboratory of Molecular Biology.

Bertolotti's research focuses on protein quality control systems in cells, due to their importance as the cellular defence against the misfolded proteins that accumulate in degenerative diseases, such as Alzheimer's, Parkinson's or Huntington's disease.[8] She is known for her work on the mechanisms governing aggregation of disease-causing proteins,[9] [10] [11] [12] [13] [14] for identifying components of cellular defense mechanisms against protein aggregation[15] [16] [17] and for the discovery of strategies to rescue cell survival under protein misfolding stress.[18] [19] [20] [21]

One of such strategies consists of selective inhibition of an eIF2 phosphatase to reduce transient protein synthesis, allowing the cell to "catch up" with the required handling of misfolded proteins.[22] Her group subsequently demonstrated that selective inhibitors had therapeutic effects in mouse models of Charcot-Marie-Tooth disease and Huntington's disease.

One of the inhibitors discovered in Bertolotti's lab, Sephin1, has passed through favourable Phase 1 clinical trials in 2019 and is being developed for Charcot-Marie-Tooth disease.[23]

Professional associations and awards

External links

Notes and References

  1. Web site: Biology. ©2020 MRC Laboratory of Molecular. Avenue. Francis Crick. Campus. Cambridge Biomedical. CB2 0QH. Cambridge. Uk. 01223 267000. Anne Bertolotti. 2020-09-30. MRC Laboratory of Molecular Biology. en-GB.
  2. Web site: pmabbs . 2022-10-14 . Anne Bertolotti appointed as Joint Head of the LMB's Neurobiology Division . 2023-03-28 . MRC Laboratory of Molecular Biology . en-GB.
  3. Web site: Biochemical Society 2018 Award Winners.
  4. Bertolotti. Anne. Zhang. Yuhong. Hendershot. Linda M.. Harding. Heather P.. Ron. David. June 2000. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nature Cell Biology. en. 2. 6. 326–332. 10.1038/35014014. 10854322. 22684712. 1476-4679.
  5. 2000-05-01. Perk Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response. Molecular Cell. en. 5. 5. 897–904. 10.1016/S1097-2765(00)80330-5. 1097-2765. Harding. Heather P.. Zhang. Yuhong. Bertolotti. Anne. Zeng. Huiqing. Ron. David. 10882126. free.
  6. Bertolotti. Anne. Ron. David. 2001-09-01. Alterations in an IRE1-RNA complex in the mammalian unfolded protein response. Journal of Cell Science. en. 114. 17. 3207–3212. 10.1242/jcs.114.17.3207 . 0021-9533. 11590247.
  7. Web site: Anne Bertolotti • iBiology. 2020-09-30. iBiology. en-US.
  8. Web site: Bertolotti A[Author] - Search Results - PubMed]. 2020-09-30. PubMed. en.
  9. Rousseau. Erwann. Dehay. Benjamin. Ben-Haïem. Léa. Trottier. Yvon. Morange. Michel. Bertolotti. Anne. 2004-06-29. Targeting expression of expanded polyglutamine proteins to the endoplasmic reticulum or mitochondria prevents their aggregation. Proceedings of the National Academy of Sciences. en. 101. 26. 9648–9653. 10.1073/pnas.0403015101. 0027-8424. 15210964. 470729. 2004PNAS..101.9648R. free .
  10. Dehay. Benjamin. Bertolotti. Anne. 2006-11-24. Critical role of the proline-rich region in Huntingtin for aggregation and cytotoxicity in yeast. The Journal of Biological Chemistry. 281. 47. 35608–35615. 10.1074/jbc.M605558200. 0021-9258. 16973603. 19848703. free.
  11. Rousseau. Erwann. Kojima. Rieko. Hoffner. Guylaine. Djian. Philippe. Bertolotti. Anne. 2009-01-16. Misfolding of Proteins with a Polyglutamine Expansion Is Facilitated by Proteasomal Chaperones. The Journal of Biological Chemistry. 284. 3. 1917–1929. 10.1074/jbc.M806256200. 0021-9258. 2615503. 18986984. free .
  12. Münch. Christian. Bertolotti. Anne. 2010-06-11. Exposure of hydrophobic surfaces initiates aggregation of diverse ALS-causing superoxide dismutase-1 mutants. Journal of Molecular Biology. 399. 3. 512–525. 10.1016/j.jmb.2010.04.019. 1089-8638. 2927901. 20399791.
  13. Münch. Christian. O’Brien. John. Bertolotti. Anne. 2011-03-01. Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells. Proceedings of the National Academy of Sciences. en. 108. 9. 3548–3553. 10.1073/pnas.1017275108. 0027-8424. 21321227. 3048161. 2011PNAS..108.3548M. free .
  14. Zhong. Zhen. Grasso. Laura. Sibilla. Caroline. Stevens. Tim J.. Barry. Nicholas. Bertolotti. Anne. 15 March 2018. Prion-like protein aggregates exploit the RHO GTPase to cofilin-1 signaling pathway to enter cells. The EMBO Journal. 37. 6. 10.15252/embj.201797822. 1460-2075. 5852416. 29496740.
  15. Suraweera. Amila. Münch. Christian. Hanssum. Ariane. Bertolotti. Anne. 2012-10-26. Failure of Amino Acid Homeostasis Causes Cell Death following Proteasome Inhibition. Molecular Cell. 48. 2. 242–253. 10.1016/j.molcel.2012.08.003. 1097-2765. 3482661. 22959274.
  16. Hanssum. Ariane. Zhong. Zhen. Rousseau. Adrien. Krzyzosiak. Agnieszka. Sigurdardottir. Anna. Bertolotti. Anne. 2014-08-21. An Inducible Chaperone Adapts Proteasome Assembly to Stress. Molecular Cell. 55. 4. 566–577. 10.1016/j.molcel.2014.06.017. 1097-2765. 4148588. 25042801.
  17. Rousseau. Adrien. Bertolotti. Anne. August 2016. An evolutionarily conserved pathway controls proteasome homeostasis. Nature. en. 536. 7615. 184–189. 10.1038/nature18943. 27462806. 4990136. 2016Natur.536..184R. 1476-4687.
  18. Tsaytler. Pavel. Harding. Heather P.. Ron. David. Bertolotti. Anne. 2011-04-01. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science. 332. 6025. 91–94. 10.1126/science.1201396. 1095-9203. 21385720. 2011Sci...332...91T. 3169931. free.
  19. Das. Indrajit. Krzyzosiak. Agnieszka. Schneider. Kim. Wrabetz. Lawrence. D'Antonio. Maurizio. Barry. Nicholas. Sigurdardottir. Anna. Bertolotti. Anne. 2015-04-10. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science. 348. 6231. 239–242. 10.1126/science.aaa4484. 1095-9203. 4490275. 25859045. 2015Sci...348..239D.
  20. Carrara. Marta. Sigurdardottir. Anna. Bertolotti. Anne. September 2017. Decoding the selectivity of eIF2α holophosphatases and PPP1R15A inhibitors. Nature Structural & Molecular Biology. 24. 9. 708–716. 10.1038/nsmb.3443. 1545-9985. 5591645. 28759048.
  21. Krzyzosiak. Agnieszka. Sigurdardottir. Anna. Luh. Laura. Carrara. Marta. Das. Indrajit. Schneider. Kim. Bertolotti. Anne. 23 August 2018. Target-Based Discovery of an Inhibitor of the Regulatory Phosphatase PPP1R15B. Cell. 174. 5. 1216–1228.e19. 10.1016/j.cell.2018.06.030. 1097-4172. 6108835. 30057111.
  22. Web site: Protein Phosphatases • iBiology. 2020-09-30. iBiology. en-US.
  23. Web site: A Combined SAD and MAD Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of IFB-088 - Tabular View - ClinicalTrials.gov. 2020-09-30. clinicaltrials.gov. en.
  24. Web site: EMBO report 2004.
  25. Web site: Dr. Anne Bertolotti – Building Bridges in Medical Sciences. 2020-09-30. en-US.
  26. Web site: EMBO announces new members for 2013. EMBO. en-gb. 2020-03-07. 2019-05-11. https://web.archive.org/web/20190511172236/http://www.embo.org/news/press-releases/2013/embo-announces-new-members-for-2013. dead.
  27. Web site: Hooke Medal Winner 2014 – Anne Bertolotti British Society for Cell Biology. en-US. 2020-03-07.
  28. Web site: Dr Anne Bertolotti The Academy of Medical Sciences. acmedsci.ac.uk. 2020-03-07.
  29. Web site: 2019-08-08. 7 novembre 2019: Prof. Anne Bertolotti - Frontiers in biomedicine - UNIGE. 2020-09-30. www.unige.ch. en.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Anne Bertolotti".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.