Anne Bertolotti

Last updated
Anne Bertolotti
Alma materUniversity of Strasbourg, France
AwardsEMBO 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)

Contents

Scientific career
FieldsBiochemistry

Cell Biology

Neuroscience
InstitutionsIGBMC

Skirball Institute of Biomolecular Medicine in the New York University School of Medicine Ecole Normale Superieure, Paris France Inserm

MRC Laboratory of Molecular Biology
Website https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/anne-bertolotti/

Anne Bertolotti FMedSci [1] is a French biochemist and cell biologist who works as Programme Leader at the MRC Laboratory of Molecular Biology (MRC LMB) in Cambridge, UK. [2] In 2022 she was appointed Head of the MRC LMB's Neurobiology Division. [3] 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. [1] [4]

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). [5]

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. [5] [6] [7] [8]

In 2001, Bertolotti became an Inserm Associate Professor at Ecole Normale Superieure, Paris. [9] In 2006, she became a group leader at the MRC Laboratory of Molecular Biology. [5]

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. [4] [10] She is known for her work on the mechanisms governing aggregation of disease-causing proteins, [11] [12] [13] [14] [15] [16] for identifying components of cellular defense mechanisms against protein aggregation [17] [18] [19] and for the discovery of strategies to rescue cell survival under protein misfolding stress. [20] [21] [22] [23]

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. [20] [24] Her group subsequently demonstrated that selective inhibitors had therapeutic effects in mouse models of Charcot-Marie-Tooth disease and Huntington's disease. [21] [23] [24]

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. [25]

Professional associations and awards

References

  1. 1 2 3 "Dr Anne Bertolotti | The Academy of Medical Sciences". acmedsci.ac.uk. Retrieved 2020-03-07.
  2. ↑ Biology, ©2020 MRC Laboratory of Molecular; Avenue, Francis Crick; Campus, Cambridge Biomedical; CB2 0QH, Cambridge; Uk. 01223 267000. "Anne Bertolotti". MRC Laboratory of Molecular Biology. Retrieved 2020-09-30.{{cite web}}: CS1 maint: numeric names: authors list (link)
  3. ↑ pmabbs (2022-10-14). "Anne Bertolotti appointed as Joint Head of the LMB's Neurobiology Division". MRC Laboratory of Molecular Biology. Retrieved 2023-03-28.
  4. 1 2 3 "Biochemical Society 2018 Award Winners".
  5. 1 2 3 4 "Hooke Medal Winner 2014 – Anne Bertolotti | British Society for Cell Biology" . Retrieved 2020-03-07.
  6. ↑ 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. 2 (6): 326–332. doi:10.1038/35014014. ISSN   1476-4679. PMID   10854322. S2CID   22684712.
  7. ↑ Harding, Heather P.; Zhang, Yuhong; Bertolotti, Anne; Zeng, Huiqing; Ron, David (2000-05-01). "Perk Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response". Molecular Cell. 5 (5): 897–904. doi: 10.1016/S1097-2765(00)80330-5 . ISSN   1097-2765. PMID   10882126.
  8. ↑ Bertolotti, Anne; Ron, David (2001-09-01). "Alterations in an IRE1-RNA complex in the mammalian unfolded protein response" . Journal of Cell Science. 114 (17): 3207–3212. doi:10.1242/jcs.114.17.3207. ISSN   0021-9533. PMID   11590247.
  9. ↑ "Anne Bertolotti • iBiology". iBiology. Retrieved 2020-09-30.
  10. ↑ "Bertolotti A[Author] - Search Results - PubMed". PubMed. Retrieved 2020-09-30.
  11. ↑ 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. 101 (26): 9648–9653. Bibcode:2004PNAS..101.9648R. doi: 10.1073/pnas.0403015101 . ISSN   0027-8424. PMC   470729 . PMID   15210964.
  12. ↑ 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. doi: 10.1074/jbc.M605558200 . ISSN   0021-9258. PMID   16973603. S2CID   19848703.
  13. ↑ 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. doi: 10.1074/jbc.M806256200 . ISSN   0021-9258. PMC   2615503 . PMID   18986984.
  14. ↑ 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. doi:10.1016/j.jmb.2010.04.019. ISSN   1089-8638. PMC   2927901 . PMID   20399791.
  15. ↑ 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. 108 (9): 3548–3553. Bibcode:2011PNAS..108.3548M. doi: 10.1073/pnas.1017275108 . ISSN   0027-8424. PMC   3048161 . PMID   21321227.
  16. ↑ 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). doi:10.15252/embj.201797822. ISSN   1460-2075. PMC   5852416 . PMID   29496740.
  17. ↑ 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. doi:10.1016/j.molcel.2012.08.003. ISSN   1097-2765. PMC   3482661 . PMID   22959274.
  18. ↑ 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. doi:10.1016/j.molcel.2014.06.017. ISSN   1097-2765. PMC   4148588 . PMID   25042801.
  19. ↑ Rousseau, Adrien; Bertolotti, Anne (August 2016). "An evolutionarily conserved pathway controls proteasome homeostasis". Nature. 536 (7615): 184–189. Bibcode:2016Natur.536..184R. doi:10.1038/nature18943. ISSN   1476-4687. PMC   4990136 . PMID   27462806.
  20. 1 2 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. Bibcode:2011Sci...332...91T. doi: 10.1126/science.1201396 . ISSN   1095-9203. PMID   21385720. S2CID   3169931.
  21. 1 2 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. Bibcode:2015Sci...348..239D. doi:10.1126/science.aaa4484. ISSN   1095-9203. PMC   4490275 . PMID   25859045.
  22. ↑ 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. doi:10.1038/nsmb.3443. ISSN   1545-9985. PMC   5591645 . PMID   28759048.
  23. 1 2 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. doi:10.1016/j.cell.2018.06.030. ISSN   1097-4172. PMC   6108835 . PMID   30057111.
  24. 1 2 "Protein Phosphatases • iBiology". iBiology. Retrieved 2020-09-30.
  25. ↑ "A Combined SAD and MAD Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of IFB-088 - Tabular View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-09-30.
  26. ↑ "EMBO report 2004" (PDF).
  27. ↑ "Dr. Anne Bertolotti – Building Bridges in Medical Sciences" . Retrieved 2020-09-30.
  28. ↑ "EMBO announces new members for 2013". EMBO. Archived from the original on 2019-05-11. Retrieved 2020-03-07.
  29. ↑ "7 novembre 2019: Prof. Anne Bertolotti - Frontiers in biomedicine - UNIGE". www.unige.ch. 2019-08-08. Retrieved 2020-09-30.
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