Dr Anne Bertolotti
Dr Anne Bertolotti is pleased to consider applications from prospective PhD students.
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.
Amyotrophic lateral sclerosis
Molecular and cell biology
No collaborators listed
Hanssum A, Zhong Z, Rousseau A, Krzyzosiak A, Sigurdardottir A, Bertolotti A (2014), “An Inducible Chaperone Adapts Proteasome Assembly to Stress.” Mol Cell Details
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
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
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
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
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
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
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
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
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
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
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
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
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