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Home > Research Leaders > A to G > Anne Bertolotti
Anne Bertolotti nb

Anne Bertolotti

Understanding and preventing the deposition of misfolded proteins


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Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS) are devastating and affect an increasing number of individuals in the ageing population. Theses diseases are caused by the progressive dysfunction and death of specific nerve cells in selective regions of the brain due to the accumulation of specific proteins of aberrant shape.

The disease-causing proteins are expressed throughout life but neurodegenerative diseases are mostly late-onset. This suggests that the different disease-causing proteins gradually become detrimental over time. While it is now well established that misfolded proteins cause distinct neurodegenerative diseases, why they accumulate remains largely unclear. Cells normally strive to ensure that proteins get correctly folded and indeed all cells have powerful and sophisticated protein quality control systems that very efficiently handle potentially harmful proteins for decades. However, the protein quality control mechanisms seem to gradually fail with age, leading to the accumulation of misfolded proteins with the resulting catastrophic consequences for cells and organisms.

My long-term goal is to understand the mechanisms that govern the deposition of misfolding-prone proteins, why they persist in aged cells and to identify strategies that could reduce the burden of misfolded proteins for cells and organisms.

We have made some progress towards this goal and contributed to our understanding of the mechanisms governing aggregation of disease-related proteins. Moreover, we have identified potent strategies to rescue cell survival under protein misfolding stress, a condition underlying many diseases.

The work of my lab focuses on fundamental cell biological processes with the view that some of our discoveries will benefit human health.

Fully funded post doc positions available

Protein-Misfolding

Selected Papers

  • Krzyzosiak, A., Sigurdardottir, A., Luh, L., Carrara, M., Das, I., Schneider, K., & Bertolotti, A. (2018)
    Target-Based Discovery of an Inhibitor of the Regulatory Phosphatase PPP1R15B.
    Cell 174(5): 1216–1228.e19.
    • iBiology Talk - Protein Phosphatases
  • Carrara, M., Sigurdardottir, A., & Bertolotti, A. (2017)
    Decoding the selectivity of eIF2α holophosphatases and PPP1R15A inhibitors.
    Nat Struct Mol Biol. 24(9): 708-716.
  • Rousseau, A., Bertolotti, A. (2016)
    An evolutionarily conserved pathway controls proteasome homeostasis.
    Nature 536(7615): 184-9.
    • Paper in Nature and pdf
    • Nature News & Views
  • Das, I., Krzyzosiak, A., Schneider, K., Wrabetz, L., D'Antonio, M., Barry, N., Sigurdardottir, A. and Bertolotti, A. (2015)
    Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit.
    Science 348: 239-242.
    • Editor’s Choice. Science Signaling. (2015). 8(372),ec96-ec96.
    • Research Highlights. Nat. Chem. Biol. (2015). 11(6), 380–380.
    • Research Highlights. Nat. Rev. Mol. Cell. Biol. (2015). 16(6), 328–328.
    • Research Highlights. Nature Reviews Drug Discovery. (2015). 14(386).
    • Recommended by Faculty of 1000.
    • Abstract, Reprint and Full Text
  • Hanssum, A., Zhong, Z., Rousseau, A., Krzyzosiak, A., Sigurdardottir, A. and Bertolotti, A. (2014)
    An inducible chaperone adapts proteasome assembly to stress
    Mol. Cell 55: 566-577.
    • Journal Cover
    • Editor’s Choice. Science. (2014). 345.
    • Research Highlights. Nat. Rev. Mol. Cell. Biol. (2014). 15. 562-563.
  • Suraweera, A. , Münch, C., Hanssum, A. and Bertolotti, A. (2012)
    Failure of amino acid homeostasis causes cell death following proteasome inhibition.
    Mol. Cell 48(2): 242-253.
  • Tsaytler, P., Harding, H. P., Ron, D. and Bertolotti, A. (2011)
    Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis.
    Science 332: 91-94.
    • Comment in Science. 2011 Apr 1;332(6025):44-5.
  • Munch, C., O'Brien, J. and Bertolotti, A. (2011)
    Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells.
    Proc Natl Acad Sci U.S.A. 108: 3548-3553.

Group Members

  • Claudia De Miguel
  • Agnieszka Fatalska
  • George Hodgson
  • Shashank Rai
  • Maria Szaruga-Bracke
  • Sigurdur Thorkelsson

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Research Leaders

  • A to G
    • Matteo Allegretti
    • Radu Aricescu
    • David Barford
    • Buzz Baum
    • Anne Bertolotti
    • Tanmay Bharat
    • Mariann Bienz
    • Simon Bullock
    • Albert Cardona
    • Andrew Carter
    • Jason Chin
    • Gerry Crossan
    • Emmanuel Derivery
    • Michel Goedert
    • Julian Gough
    • Ingo Greger
  • H to M
    • Michael Hastings
    • Ramanujan Hegde
    • Richard Henderson
    • Philipp Holliger
    • Leo James
    • Gregory Jefferis
    • Patrycja Kozik
    • Madeline Lancaster
    • Jan Löwe
    • Kate McDole
    • Andrew McKenzie
    • Harvey McMahon
    • Liz Miller
    • Sean Munro
    • Garib Murshudov
  • N to S
    • Kelly Nguyen
    • John O’Neill
    • Lori Passmore
    • Lalita Ramakrishnan
    • Venki Ramakrishnan
    • Felix Randow
    • Jing Ren
    • Christopher Russo
    • Benjamin Ryskeldi-Falcon
    • Julian Sale
    • William Schafer
    • Sjors Scheres
    • Marta Shahbazi
    • John Sutherland
  • T to Z
    • Chris Tate
    • Marco Tripodi
    • Ana Tufegdžić Vidaković
    • Roger Williams
    • Joseph Yeeles
    • Suyang Zhang
    • Marta Zlatic
  • Emeritus
    • Brad Amos
    • Tony Crowther
    • Phil Evans
    • Alan Fersht
    • Michael Gait
    • Rob Kay
    • John Kendrick-Jones
    • John Kilmartin
    • Peter Lawrence
    • Andrew Leslie
    • David Neuhaus
    • Hugh Pelham
    • Daniela Rhodes
    • Murray Stewart
    • Andrew Travers
    • Nigel Unwin
    • Greg Winter
  • LMB Fellows
  • Molecular Immunity Unit

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