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Elena Giulotto

Academic position:
Full Professor
E-mail:
elena.giulotto (at) unipv.it
Phone number:
+39 0382 985541 (office); +39 0392 985540 (lab)
Fax:
+39 0382 528496
Website:
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Department:
Department of Biology and Biotechnology "Lazzaro Spallanzani"

Courses

2017/2018
Advanced Molecular Biology
2016/2017
Advanced Molecular Biology

Exams

No exams

Curriculum vitae

Elena Giulotto obtained a degree in Biology cum laude at the University of Pavia and was postgraduate student in Genetics in the same University.
She was postdoctoral fellow in the Biochemistry Department, Stanford University, Stanford, USA (1980-1983) and at the Imperial Cancer Research Fund, London, UK (1984-1986).
She is now Full Professor in Molecular Biology at the University of Pavia, Faculty of Sciences.
Elena Giulotto is head of the Molecular and Cellular Biology Laboratory, Department of Genetics and Microbiology. The laboratory is funded by grants from European Community, Ministry of Education, Fondazione Cariplo, Biotecnological Companies. The research activity is focused on the cellular and molecular biology of mammalian cells, addressing particularly the m
echanisms of chromosomal instability.

Summary of recent and ongoing research 
Telomeres
Mammalian chromosomes are linear DNA molecules containing peculiar structures at their termini, called telomeres, which are essential for the maintenance of chromosome integrity. Genomic instability associated with telomere dysfunction can lead to tumorigenesis. Telomeric DNA is composed of tandem repetitions of the TTAGGG hexamer, synthesized by the specialized enzyme telomerase. In addition to their location at terminal positions, telomeric-like repeats are also present at internal sites (ITSs). Using molecular, cytogenetic and bioinformatic approaches we addressed the question as to how such sequences arise and showed that they were inserted in the genomes during the repair of DNA breaks that occurred in the germ-line during evolution. Our analysis strongly suggested that ITSs were inserted at break sites by telomerase, indicating that this enzyme, besides its role in telomere maintenance, may be involved in DNA repair. We are currently studying the role of human ITSs in the regulation of gene expression and chromosome stability. We recently described, in collaboration with the group of Joachim Lingner (Lausanne), another new function of telomeric DNA; telomeres, that were thought to be “silent” regions of the genome, are actively transcribed producing a heterogeneous fraction of RNA molecules (2). The involvement of this RNA fraction in telomere regulation is under study.
Centromeres
Besides telomeres, the main structure required for chromosome stability is the centromere. We discovered that, in the genus Equus (horses, asses and zebras), several centromeres are characterized by a simple sequence organization because they are evolutionarily very recent; we are therefore using them as model systems to study the molecular organization, function and evolution of mammalian centromeres.
Gene amplification
Another manifestation of genomic instability is gene amplification (copy number increase of a DNA sequence), a key mechanism for oncogene activation and drug resistance in tumor cells involving DNA breakage and repair. To study the molecular mechanisms generating amplified DNA we measured the amplification ability in tumor cells in which the expression of genes involved in the repair of DNA breaks was inhibited by “RNA interference”. These cells are hypersensitive to ionizing radiations and more prone to gene amplification than normal cells, indicating that the cellular ge
netic background can affect the response to therapy and the probability of tumor progression. Some of these studies are still ongoing with particular attention to the homologous and non-homologous pathways of DNA double-strand break repair. Taking advantage of our background in gene amplification we set up an efficient method for the construction of mammalian cell lines over-expressing exogenous proteins; joint projects with pharmaceutical companies are under way aimed at the production of recombinant therapeutic proteins.

 

10 SELECTED PUBLICATIONS

Piras FM, Nergadze SG, Magnani E, Bertoni L, Attolini C, Khoriauli L, Raimondi E, Giulotto E. (2010). Uncoupling of satellite DNA and centromeric function in the genus Equus. PLoS Genetics, 6:e1000845

 

Mondello C, Smirnova A, Giulotto E. (2010). Gene amplification, radiation sensitivity and DNA double strand-breaks. Mutation Research, 704:29-37

 

Nergadze SG, Farnung BO, Wischnewski H, Khoriauli L, Vitelli V, Chawla R, Giulotto E, Azzalin CM. (2009). CpG-island promoters drive transcription of human telomeres. RNA,  15: 2186-2194

 

Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, Macleod JN, Penedo MCT, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC. (2009). Genome sequence, comparative analysis and population genetics of the domestic horse (Equus caballus). Science, 326:  865-867

 

Salzano A, Kochiashvili N, Nergadze SG, Khoriauli L, Smirnova A, Ruiz-Herrera A, Mondello C, Giulotto E. (2009). Enhanced gene amplification in human cells knocked down for DNA-PKcs. DNA Repair, 8: 19-28

 

Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. (2007). Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science, 318: 789-801

 

Nergadze SG, Santagostino M, Salzano A, Mondello C, Giulotto E. (2007). Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution. Genome Biology, 8: R260

 

Carbone L, Nergadze SG, Magnani E, Misceo D, Cardone MF, Roberto F, Bertoni L,  Attolini C, Piras MF, De Jong P, Raudsepp T, Chowdhary BP, Guerin G, Archidiacono N, Rocchi M, Giulotto E. (2006). Evolutionary movement of centromeres in horse, donkey and zebra. Genomics, 87: 777-782

 

Rebuzzini P, Khoriauli L, Azzalin CM, Magnani E, Mondello C, Giulotto E. (2005). New mammalian cellular systems to study mutations introduced at the break site by non-homologous end-joining. DNA Repair, 4: 546-555

 

Nergadze SG, Rocchi M, Azzalin CM, Mondello C, Giulotto E. (2004). Insertion of telomeric repeats at intrachromosomal break sites during primate evolution. Genome Research, 14: 1704-1710

 

 

 

 

 

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