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 in Cambridge, UK.[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.[1][3]

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)
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
Websitehttps://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/anne-bertolotti/

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 Lazlo Tora and Pierre Chambon at Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC).[4]

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][7]

In 2001, Bertolotti became an Inserm Associate Professor at Ecole Normale Superieure, Paris.[8] In 2006, she became a group leader at the MRC Laboratory of Molecular Biology.[4]

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.[3][9] She is known for her work on the mechanisms governing aggregation of disease-causing proteins,[10][11][12][13][14][15] for identifying components of cellular defense mechanisms against protein aggregation[16][17][18] and for the discovery of strategies to rescue cell survival under protein misfolding stress.[19][20][21][22]

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.[19][23] Her group subsequently demonstrated that selective inhibitors had therapeutic effects in mouse models of Charcot-Marie-Tooth disease and Huntington’s disease.[20][22][23]

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.[24]

Professional associations and awards

References
  1. "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.
  3. "Biochemical Society 2018 Award Winners".
  4. "Hooke Medal Winner 2014 – Anne Bertolotti | British Society for Cell Biology". Retrieved 2020-03-07.
  5. 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.
  6. 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.
  7. 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. ISSN 0021-9533. PMID 11590247.
  8. "Anne Bertolotti • iBiology". iBiology. Retrieved 2020-09-30.
  9. "Bertolotti A[Author] - Search Results - PubMed". PubMed. Retrieved 2020-09-30.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. "Protein Phosphatases • iBiology". iBiology. Retrieved 2020-09-30.
  24. "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.
  25. "EMBO report 2004" (PDF).
  26. "Dr. Anne Bertolotti – Building Bridges in Medical Sciences". Retrieved 2020-09-30.
  27. User, Super. "EMBO announces new members for 2013". EMBO. Retrieved 2020-03-07.
  28. "7 novembre 2019: Prof. Anne Bertolotti - Frontiers in biomedicine - UNIGE". www.unige.ch. 2019-08-08. Retrieved 2020-09-30.
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