Dr Anne Bertolotti

Anne Bertolotti

University position

Programme leader

Dr Anne Bertolotti is pleased to consider applications from prospective PhD students.

Institutes

Medical Research Council Laboratory of Molecular Biology

Home page

http://www2.mrc-lmb.cam.ac.uk/group-l...

Research Theme

Cellular and Molecular Neuroscience

Interests

Diverse neurodegenerative diseases share a common cause: aggregation of a specific protein in selective regions of the brain.

The disease-causing proteins are expressed throughout life but neurodegenerative diseases are mostly late-onset. In fact, 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.

Our aim is to identify approaches to prevent degenerative diseases and promoting healthy ageing. Image courtesy of Leo Hillier.
Our aim is to identify approaches to prevent degenerative diseases and promoting healthy ageing. Image courtesy of Leo Hillier.
Click image to view full-size

Research Focus

Keywords

Protein misfolding

Chaperones

Proteasome

Protein aggregation

Prions

Clinical conditions

Amyotrophic lateral sclerosis

Huntington's disease

Equipment

Molecular and cell biology

Collaborators

No collaborators listed

Associated News Items


    Publications

    2015

    Das I, Krzyzosiak A, Schneider K, Wrabetz L, D'Antonio M, Barry N, Sigurdardottir A, Bertolotti A (2015), “Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit.” Science 348(6231):239-42 Details

    2014

    Hanssum A, Zhong Z, Rousseau A, Krzyzosiak A, Sigurdardottir A, Bertolotti A (2014), “An Inducible Chaperone Adapts Proteasome Assembly to Stress.” Mol Cell Details

    2012

    Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Martin MG, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, Bushell M, Mallucci GR (2012), “Sustained translational repression by eIF2α-P mediates prion neurodegeneration.” Nature 485(7399):507-11 Details

    Suraweera A, Münch C, Hanssum A, Bertolotti A (2012), “Failure of amino acid homeostasis causes cell death following proteasome inhibition.” Mol Cell 48(2):242-53 Details

    2011

    Münch C, Bertolotti A (2011), “Self-propagation and transmission of misfolded mutant SOD1: Prion or prion-like phenomenon?” Cell Cycle 10(11):1711 Details

    Münch C, O'Brien J, Bertolotti A (2011), “Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells.” Proc Natl Acad Sci U S A 108(9):3548-53 Details

    Tsaytler P, Harding HP, Ron D, Bertolotti A (2011), “Selective Inhibition of a Regulatory Subunit of Protein Phosphatase 1 Restores Proteostasis.” Science Details

    2010

    Münch C, Bertolotti A (2010), “Exposure of hydrophobic surfaces initiates aggregation of diverse ALS-causing superoxide dismutase-1 mutants.” J Mol Biol 399(3):512-25 Details

    2009

    Rousseau E, Kojima R, Hoffner G, Djian P, Bertolotti A (2009), “Misfolding of proteins with a polyglutamine expansion is facilitated by proteasomal chaperones.” J Biol Chem 284(3):1917-29 Details

    2007

    Dehay B, Weber C, Trottier Y, Bertolotti A (2007), “Mapping of the epitope of monoclonal antibody 2B4 to the proline-rich region of human Huntingtin, a region critical for aggregation and toxicity.” Biotechnol J 2(5):559-64 Details

    2006

    Dehay B, Bertolotti A (2006), “Critical role of the proline-rich region in Huntingtin for aggregation and cytotoxicity in yeast.” J Biol Chem 281(47):35608-15 Details

    2004

    Rousseau E, Dehay B, Ben-Haïem L, Trottier Y, Morange M, Bertolotti A (2004), “Targeting expression of expanded polyglutamine proteins to the endoplasmic reticulum or mitochondria prevents their aggregation.” Proc Natl Acad Sci U S A 101(26):9648-53 Details

    2002

    Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L (2002), “Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha.” Mol Cell Biol 22(24):8506-13 Details

    2001

    Bertolotti A, Ron D (2001), “Alterations in an IRE1-RNA complex in the mammalian unfolded protein response.” J Cell Sci 114(Pt 17):3207-12 Details

    Bertolotti A, Wang X, Novoa I, Jungreis R, Schlessinger K, Cho JH, West AB, Ron D (2001), “Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice.” J Clin Invest 107(5):585-93 Details

    2000

    Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D (2000), “Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response.” Nat Cell Biol 2(6):326-32 Details

    Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D (2000), “Perk is essential for translational regulation and cell survival during the unfolded protein response.” Mol Cell 5(5):897-904 Details

    Urano F, Bertolotti A, Ron D (2000), “IRE1 and efferent signaling from the endoplasmic reticulum.” J Cell Sci 113 Pt 21:3697-702 Details

    Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D (2000), “Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1.” Science 287(5453):664-6 Details

    1999

    Bertolotti A, Bell B, Tora L (1999), “The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties.” Oncogene 18(56):8000-10 Details

    1998

    Bertolotti A, Melot T, Acker J, Vigneron M, Delattre O, Tora L (1998), “EWS, but not EWS-FLI-1, is associated with both TFIID and RNA polymerase II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of TFIID and RNA polymerase II complexes.” Mol Cell Biol 18(3):1489-97 Details

    1996

    Bertolotti A, Lutz Y, Heard DJ, Chambon P, Tora L (1996), “hTAF(II)68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II.” EMBO J 15(18):5022-31 Details