toxic proteins drive brazil-italy connections · célia regina carlini laboratory of toxic proteins...
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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 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
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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
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Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012
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Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012
200 documents W-of-S+ 7000 citations
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Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012
Prof. Stirpe and Celia Carlini
September 2004
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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.
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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
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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
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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
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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
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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
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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
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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
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Ureases are nickel-dependent enzymes
Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012
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Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012
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Toxic proteins drive Brazil-Italy connections - Célia R. Carlini - Rome, March 2012
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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
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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