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Toxic proteins drive Brazil-Italy connections Célia Regina Carlini Laboratory of Toxic Proteins Dept. Biophysics & Center of Biotechnology Universidade Federal do Rio Grande do Sul Porto Alegre, RS - Brazil Rome , March 2012

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  • Toxic proteins drive Brazil-Italy connections

    Célia Regina Carlini

    Laboratory of Toxic Proteins

    Dept. Biophysics & Center of Biotechnology

    Universidade Federal do Rio Grande do Sul

    Porto Alegre, RS - Brazil

    Rome , March 2012

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    Toxic proteins in plants: role in defense mechanisms – abundant in seeds

    – lethal to vertebrates, invertebrates, bacteria, fungi, viruses

    Classes of toxic proteins in plants:

    Lectins: binding to carbohydrate

    Ribosome-inactivating proteins (RIPs): inhibition of protein synthesis

    Inhibitors of enzymes: anti-nutrional effects

    Ureases: enzymatic and non-enzymatic effects

    Etc…

    Ribosome-inactivating proteins (RIPs): inhibition of protein synthesis

    Ureases: enzymatic and non-enzymatic effects

  • Ribosome-inactivating proteins from plants:

    Ricin (castor bean)

    among the deadest toxins ever known

    Abrin (Abrus precatorius)

    �lethal dose in mammals: nanograms/kg

    �Mechanism of action: enzymes that modify ribosomes causing

    inhibition of protein synthesis

    �Biological role: plant protection against viruses ?

    �Potential applications:

    �Chemical weapons – murder of KGB dissidents in London - Cold War

    �Immunotoxins– “custom-made” drugs against cancer

    – enzymatic portion of a RIP fused to

    an anti-cancer immunoglobulin

    – very active field of research

    W-of-S: 3630 documents (140 in 2011-12)

    Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    A

    Bricin

    antibody

    immunotoxin

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    200 documents W-of-S+ 7000 citations

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    Prof. Stirpe and Celia Carlini

    September 2004

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    In 2004, I invited Prof. Stirpe to contribute a

    review article on RIPs to a special issue of

    Toxicon, which I edited.

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    Visit to Bologna, April 2006: Jorge Guimarães, Sybil Stirpe, Fiorenzo Stirpe and Célia Carlini

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    Ph.D. thesis of Lucia Bertholdo Vargas

    RIPs are involved in plant protection against insects

  • CO + NH2 3NH3

    H O2

    2NH

    O

    CUrease

    NH2 C

    O

    NH2

    Urease

    Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    – non-enzymatic properties ?

    2001 – first report by our group showing that ureases display several biological

    properties not related to hydrolysis of urea

  • Helicobacter pyloriHelicobacter pyloriHelicobacter pyloriHelicobacter pylori

    � Gram-negative bacterium, causative agent of gastritis, ulcers and stomach cancer

    � 10%-15% of the bacterium total protein is urease; alkalinization of the stomach acidity due to

    urease activity is important for gastric colonization by the bacteria.

    Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    XVI World Congress of International Society on Toxinology – Brazil, 2009

    Célia Carlini

    President of the Scientific Committee

    Conferences:Prof. Cesare Montecucco

    Universitá di Padova

    Redi Award lecture - Clostridial Toxins

    Prof. Fiorenzo Stirpe

    Universitá di Bologna

    Toxic and non-toxic RIPS

    Dr. Marina De Bernard

    Venetian Institute of Molecular Medicine

    Helicobacter pylori toxins

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    Cesare Montecucco (Italy), Dulcineide Magalhães (Brazil), Célia Carlini (Brazil), Marina De

    Bernard (Italy), Yoshio Yamaoka (USA)

    XVI World Congress of the International Society on Toxinology

    Recife, PE, Brazil – march 2009

    Symposium: Helicobacter pylori Helicobacter pylori Helicobacter pylori Helicobacter pylori toxins

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    Dra. Marina De Bernard

    Dr. Deiber Olivera-Severo

    CAPES post-doctoral fellow

    10 monthsBacterial and plant ureases

  • Ureases are nickel-dependent enzymes

    Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

  • Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012

    Universitá di Bologna, September 2010:

    Deiber Olivera-Severo, Rafael Real Guerra (3 months – Brazilian research grant), Celia Carlini, Barbara Zambelli, Francesco Musiani, Stefano Ciurli

    On-going studies on Urease-derived peptides and accessory proteins

  • Thank you for your attention.

    Visit us at www.ufrgs.br/laprotox

    Laboratory of Toxic Proteins

    UFRGS, Porto Alegre, RS

    Brazil

    Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012