Anne BertolottiFMedSci[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]
Anne Bertolotti
Alma mater
University of Strasbourg, France
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)
Scientific career
Fields
Biochemistry
Cell Biology
Neuroscience
Institutions
IGBMC
Skirball Institute of Biomolecular Medicine in the New York University School of Medicine
Ecole Normale Superieure, Paris France
Inserm
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 careeredit
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]
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]
^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.
^ abcd"Hooke Medal Winner 2014 – Anne Bertolotti | British Society for Cell Biology". Retrieved 2020-03-07.
^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.
^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.
^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.
^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. PMC470729. PMID 15210964.
^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.
^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. PMC2615503. PMID 18986984.
^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. PMC2927901. PMID 20399791.
^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. PMC3048161. PMID 21321227.
^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. PMC5852416. PMID 29496740.
^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. PMC3482661. PMID 22959274.
^"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.