Informação para Programa MIT-Portugal

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Informação para Programa MIT-Portugal

Name: Rui M. Meireles Brito

Position: Tenured Assistant Professor Department of Chemistry

Faculdade de Ciências e Tecnologia

Universidade de Coimbra, Coimbra, Portugal. E-mail address: [email protected]

Research area: Structural and Computational Biology Education

1993 Equivalence to the degree of "Doutor" Universidade de Coimbra, Coimbra, Portugal

1992 PhD in Biochemistry

Department of Biochemistry and Cell Biology Rice University, Houston, Texas, U.S.A. 1984 "Licenciatura" in Biochemistry

Universidade de Coimbra, Coimbra, Portugal Previous positions

2004 Visiting Scientist (1 month)

Johns Hopkins University

Baltimore, USA

1993-1998 Assistant Professor

Universidade de Coimbra, Coimbra, Portugal. 1996 Visiting Scientist (3 months)

NMR Facility, Medical School

University of Cincinnati, Cincinnati, Ohio, U.S.A. 1993-1995 Manager of NMR Facility

Universidade de Coimbra, Coimbra, Portugal.

1992-1993 Post-Doctoral Fellow

Oxford Center for Molecular Sciences Oxford University, Oxford, United Kingdom

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(Advisor: Professor Christopher M. Dobson). 1985-1992 Graduate Study at:

Department of Biochemistry and Cell Biology Rice University, Houston, Texas, U.S.A. (Advisor: Professor Frederick B. Rudolph) Joint Research at:

Biochemical Magnetic Resonance Laboratory

The University of Texas Medical School, Houston, Texas, U.S.A. (Advisor: Professor Paul R. Rosevear)

1984-1985 Teaching Assistant

Universidade de Coimbra, Coimbra, Portugal

Research activities

MAIN SCIENTIFIC AREA OF RESEARCH:

Structural and Computational Biology MAIN RESEARCH TOPICS:

Protein structure, stability and folding: their relationship to function and pathology. Molecular mechanisms of amyloid formation. Peptide conformational plasticity and molecular mechanisms of biomembrane insertion.

MAIN RESEARCH METHODOLOGIES:

NMR, CD, Fluorescence, Molecular Modeling and Molecular Dynamics. FELLOWSHIPS: 1985-1986 Graduate Studentship

Rice University

Houston, Texas, U.S.A.

1985-1992 Fulbright Fellow

Fulbright Travel Grant, U.S.A.

1986-1992 Graduate Studentship

Robert Welch Foundation

Texas, U.S.A.

1996 NATO Science Fellowship (3 months)

Visiting Scientist

NMR Facility, Medical School

University of Cincinnati, Cincinnati, Ohio, U.S.A. 1997 The Wellcome Trust Travel Grant, U.K.

Short Term Collaborative Research Visit Oxford Centre for Molecular Sciences Oxford University, Oxford, U.K. 1997 INIDA Program (Portugal/Germany)

Short Term Collaborative Research Visit Biozentrum, University of Wuerzburg, Germany 2002 Luso-American Foundation Travel Grant

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Rice University, Houston, USA.

2004 Luso-American Foundation Short Term Fellowship

Visiting Scientist

Johns Hopkins University, Baltimore, USA.

RESEARCH 1996-1999 Program “Base de Investigação Científica e

GRANTS: Tecnológica”, Portugal

(PBICT/C/BIO/1973/95)

"Structure, Stability and Dynamics of Interleukin-4 Mutants: Lessons for Protein Engineering in Four-Helix Bundles"

1996-1999 Program PRAXIS XXI, Portugal

(PRAXIS/2/2.1/SAU/1287/95)

"Tridimensional Structure, Stability and Dynamics of Transthyretin Variants"

1997-2000 Program PRAXIS XXI, Portugal

(PRAXIS/PCNA/P/BIO/73/96)

"Experimental and Theoretical Studies on Protein Folding: Small Changes, Different Structures, Large Consequences"

1998-2001 BIOMED 2, European Union

(BMH4-CT98-3689)

"TTR-Associated Amyloidosis, Mechanism for Amyloid Formation and Development of Therapeutic Strategies" 1999-2001 Program PRAXIS XXI, Portugal

(PRAXIS/SAU/14095/98)

“Molecular Mechanisms of Amyloidogenesis by Transthyretin”

2001-2004 Program POCTI, Portugal

(POCTI/BIO/35685 /2000)

“The Role of Disulphide Bridges on Human Interleukin-4 Stability, Folding and Biological Activity”

2004-2007 Programa POCTI, Portugal

(POCTI/BME/49583/2002)

"Amyloid Fibril Formation by Transthyretin: searching for the amyloidogenic intermediates"

2005 Programa Nacional de Re-Equipamento Científico

(REEQ-1028/BIO/2005)

"Estrutura e Função de Proteínas"

2006 Programa Nacional de Re-Equipamento Científico

(REEQ-481/QUI/2006)

"Small Molecule High Resolution Nuclear Magnetic Resonance Facility"

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Teaching activities

GRADUATE AND 1984-1985 Teaching Assistant UNDERGRADUATE Faculdade de Ciências e Tecnologia

COURSES Universidade de Coimbra, Coimbra, Portugal.

Undergraduate Courses: "Biophysics" and "Enzymology"

1986-1987 Tutorial Leader

Department of Biochemistry and Cell Biology Rice University, Houston, U.S.A.

Undergraduate Course: "General Biochemistry"

1993-present Assistant Professor

Universidade de Coimbra, Coimbra, Portugal.

Undergraduate Courses in the Department of Biochemistry: "Physical Biochemistry", "Biochemical Technology II", "Biochemistry I".

Undergraduate Courses in the Department of Chemistry: “Introduction to Chemical Laboratories”, “Protein Physical-Chemistry”, “Bio-Organic Chemistry”, “Seminar in Biological Macromolecules”.

1994 Co-organizer and Lecturer in the Graduate Course: "NMR in Biochemistry and Biophysics"

PhD Program in Biomedicine

Instituto de Biologia Experimental e Biomedicina Universidade de Coimbra, Coimbra, Portugal. 1994 Lecturer in the Graduate Course:

"Structure and Function of Macromolecules", Doctorate Program in Molecular Biology

Fundação Calouste Gulbenkian, Lisboa, Portugal. 1994 Lecturer in the Undergraduate Course:

"Structure and Function of Proteins"

Instituto de Ciências Biomédicas Abel Salazar Universidade do Porto, Porto, Portugal. 1995 Lecturer in the Graduate Course:

"From Primary to Three-dimensional Structure of Proteins: Concepts, Methods and Applications"

Doctorate Program in Molecular Biology

Fundação Calouste Gulbenkian, Lisboa, Portugal. 1995-1998 Lecturer in the Graduate Course:

"Biochemistry G200: Proteins" M.Sc. Program in Cell Biology

Universidade de Coimbra, Coimbra, Portugal. 1998 Lecturer in the Undergraduate Course:

"Structure and Function of Proteins"

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Universidade do Porto, Porto, Portugal. 1999-present Lecturer in the Graduate Course

"Spectroscopic Methods"

M.Sc. Program in Chemistry Department of Chemistry

Universidade de Coimbra, Portugal 2004-present Lecturer of the Graduate Course

"Elementos Químicos da Vida"

M.Sc. Program in "Ensino de Física e Química" Department of Chemistry

Universidade de Coimbra, Portugal 2006 Co-organizer of the Graduate Course

"Structural Biology: Amyloidosis"

http://cnc.cj.uc.pt/BEB/courses0506/strucbiol.php

PhD program in Experimental Biology and Biomedicine

Universidade de Coimbra

2006 Co-organizer and Lecturer in the Graduate Course "Structural Biology - Protein Structure: Why study it? How to study it?"

http://cnc.cj.uc.pt/BEB/course0607.php

PhD program in Experimental Biology and Biomedicine

Universidade de Coimbra

SCIENTIFIC CONCLUDED THESIS:

ADVISING:

1995 Gadolinium Chelates as Paramagnetic Relaxation

Agents in the Study of Protein Surfaces Rui de Albuquerque Carvalho

MSc in Cell Biology

Universidade de Coimbra, Portugal

1995 Preparation and Characterization of Sacarose

Derivatives for Enzyme Imobilization Francisco Pedro da Silva Pinto

“Licenciatura” (BSc) Thesis in Biochemistry Universidade de Coimbra, Portugal

1995 Study of Protein Surfaces and Stability using

Gadolinium Chelates

Joaquim Rui de Castro Rodrigues

1996 Multidimensional NMR Comparative Study between

Recombinant Human Wild-Type Interleukin-4 and the C24T Mutein

Artur Jorge Figueira de Freitas

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1997 Structural Characterization and Dynamics of the C24T Variant of Human Interleukin-4 by Multidimensional NMR

Daniela Maria Barroso de Moura Cipreste Vaz “Licenciatura” (BSc) Thesis in Biochemistry Universidade de Coimbra, Portugal

1997 Study of the Aggregation State in Solution of Wild Type Transthyretin and one Amyloidogenic Variant

Filomena Maria Marques da Silva

1997 Study of the Isotopic Effect on Protein Stability Nuno Ricardo Santos Loureiro da Silva Ferreira “Licenciatura” (BSc) Thesis in Biochemistry Universidade de Coimbra, Portugal

2000 Effect of the Chemical Environment on the

Tridimensional Structure of the Peptide δ-toxin from Staphilococcus aureus

Carla Sofia Fernandes Barreira

“Licenciatura” (BSc) Thesis in Industrial Chemistry Universidade de Coimbra, Portugal

2002 Clues for the Understanding of the Molecular

Mechanisms of Amyloid Fibril Formation by Transthyretin

Alexandre Luís de Matos Botica Côrtes Quintas PhD in Biological Chemistry

2002 Study of the Dissociation Equilibrium in Variants of Transthyretin

Margarida Isabel Ramos Roque

“Licenciatura” (BSc) Thesis in Chemistry Universidade de Coimbra, Portugal

2002 Unfolding Kinetics and Amyloidogenesis in

Transthyretin

Bárbara Joana de Almeida Henriques “Licenciatura” (BSc) Thesis in Chemistry Universidade de Coimbra, Portugal

2003 Human Interleukin-4 Conformational Stability: the role of disulphide bridges

Daniela Maria Barroso de Moura Cipreste Vaz MSc in Cell Biology

2003 Amiloidogenesis, Protein Stability and

Protein-Membrane Interactions in Transthyretin and Prions Joana Rita Simões Correia

BSc Thesis in Chemistry

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2004 Studies on the Interaction of Transthyretin with Small Ligands

Carina Maria da Silva Costa BSc Thesis in Chemistry

2005 Studies on the Aggregation of the Protein Transthyretin Bruno Emanuel Correia

BSc Thesis in Chemistry

Universidade de Coimbra, Portugal 2006 Refolding Studies in Transthyretin Variants

Zaida Catarina Lourenço Almeida BSc Thesis in Chemistry

2006 Molecular Dynamics Studies of Subunit Denaturation of Transthyretin at High Temperature

Tirsa Leonor Dias Romão Lobo dos Santos BSc Thesis in Chemistry

Selected publications PEER-REVIEWED PUBLICATIONS:

1. Brito, R. M. M. and Vaz, W. L. C. (1986). Determination of the Critical Micelle Concentration of Surfactants Using the Fluorescent Probe N-phenyl-1-naphtylamine. Anal. Biochem. 152, 250-255.

2. Brito, R. M. M., Reddick, R., Bennett, G. N., Rudolph, F. B., and Rosevear, P. R. (1990). Characterization and Stereochemistry of Cofactor Oxidation by a Type II Dihydrofolate Reductase. Biochemistry 29, 9825-9831.

3. Sweeney, H. L., Brito, R. M. M., Rosevear, P. R. and Putkey, J. A. (1990). The Low-Affinity Ca2+-Binding Sites in Cardiac / Slow Skeletal Muscle Troponin C Perform Distinct Functions: Site I alone cannot trigger contraction. Proc. Nat. Acad. Sci. USA 87, 9538-9542.

4. Brito, R. M. M., Rudolph, F. B., and Rosevear, P. R. (1991). Conformation of NADP+ Bound to a Type II Dihydrofolate Reductase. Biochemistry 30, 1461-1469.

5. Brito, R. M. M., Putkey, J. A., Strynadka, N. C. J., James, M. N. G., and Rosevear, P. R. (1991). Comparative NMR Studies on Cardiac Troponin C and a Mutant Incapable of Binding Calcium at Site II. Biochemistry 30, 10236-10245.

6. Krudy, G. A., Brito, R. M. M., Putkey, J. A., and Rosevear, P. R. (1992). Conformational Changes in the Metal-Binding Sites of Cardiac Troponin C Induced by Calcium Binding. Biochemistry 31, 1595-1602.

7. Brito, R. M. M., Krudy, G. A., Negele, J. C., Putkey, J. A., and Rosevear, P. R. (1993). Calcium Plays Distinctive Structural Roles in the N- and C-terminal Domains of Cardiac Troponin C. J. Biol. Chem. 268, 20966-20973.

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8. Lin, X., Krudy, G. A., Howarth, J., Brito, R. M. M., Rosevear, P. R. and Putkey, J. A. (1994). Assignment and Calcium Dependence of Methionyl εC and εH Resonances in Cardiac Troponin C. Biochemistry 33, 14434-14442.

9. Quintas, A., Saraiva, M. J. M., Brito, R. M. M. (1997). The Amyloidogenic Potential of Transthyretin Variants Correlates with their Tendency to Aggregate in Solution. FEBS Letters 418, 297-300.

10. Gasmi-Seabrook, G. M. C., Howarth, J. W., Finley, N., Abusamhadneh, E., Gaponenko, V., Brito, R. M. M., Solaro, R. J., and Rosevear, P. R. (1999). Solution Structures of the C-Terminal Domain of Cardiac Troponin C Free and Bound to the N-C-Terminal Domain of Cardiac Troponin I. Biochemistry 38, 8313-8322.

11. Quintas, A., Saraiva, M. J. M., Brito, R. M. M. (1999). The Tetrameric Protein Transthyretin Dissociates to a Non-Native Monomer in Solution: A Novel Model for Amyloidogenesis. J. Biol. Chem. 274, 32943-32949.

12. Shnyrov, V. L., Villar, E., Zhadan, G. G., Sanchez-Ruiz, J. M., Quintas, A., Saraiva, M. J. M., and Brito, R. M. M. (2000). Comparative Calorimetric Study of Non-amyloidogenic and Amyloidogenic Variants of the Homotetrameric Protein Transthyretin. Biophysical Chem. 88, 61-67.

13. Egas, C., Lavoura, N., Resende, R., Brito, R. M. M., Pires, E., Lima, M. C. P., and Faro, C. (2000). The Saposin-like Domain of the Plant Aspartic Proteinase Precursor is a Potent Inducer of Vesicle Leakage. J. Biol. Chem. 275, 38190-38196.

14. Quintas, A., Saraiva, M. J. M., and Brito R. M. M. (2000). "New Insights into Amyloid Fibril Formation by Transthyretin" in "Lipid Metabolism and Related Pathology”, Vol. I, pp 93-99, Ed. M. J. Halpern.

15. Quintas, A., Vaz, D. C., Saraiva, M. J. M., and Brito, R. M. M. (2001). “Partial Unfolding of the Non-Native Monomer is the Key Event in Transthyretin Amyloidogenesis” in "Amyloid and Amyloidosis", Proceedings of the IXth International Symposium on Amyloidosis, Budapest, Hungary, Ed. Miklos Bely and Agnes Apathy, pp. 337-340.

16. Quintas, A., Vaz, D. C., Cardoso, I., Saraiva, M. J. M., and Brito, R. M. M. (2001). Tetramer Dissociation and Monomer Partial Unfolding Precedes Protofibril Formation in Amyloidogenic Transthyretin Variants. J. Biol. Chem. 276, 27207-27213.

17. Brito, R. M. M., Damas, A. M., and Saraiva, M. J. S. (2003). Amyloid Formation by Transthyretin: From Protein Stability to Protein Aggregation (review). Current Medicinal Chemistry - Immun. Endoc. & Metab. Agents 3, 349-360.

18. Brito, R. M. M., Dubitzky, W., and Rodrigues, J. R. (2004). Protein Folding and Unfolding Simulations: a New Challenge for Data Mining. OMICS A Journal of Integrative Biology 8, 153-166.

19. Rodrigues, J. R. and Brito, R. M. M. (2004). How important is the role of compact denatured states on amyloid formation by transthyretin? In "Amyloid and Amyloidosis", pp. 323-325, Eds. Gilles Grateau, Robert A. Kyle and Martha Skinner, CRC Press.

20. Stahl, F., Berrar, D., Silva, C., Rodrigues, J. R., Brito, R. M. M. and Dubitzky, W. (2005). Towards Data Warehousing and Mining of Protein Unfolding Simulation Data. J. Clinical Monitoring and Computing 19, 307-317.

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21. Azevedo, P. J., Silva, C. G., Rodrigues, J. R., Loureiro-Ferreira, N. and Brito, R. M. M. (2005). Detection of Hydrophobic Clusters in Molecular Dynamics Protein Unfolding Simulations Using Association Rules. Lecture Notes in Computer Science 3745, 329-337. 22. Bertrand, A., Brito, R. M., Alix, A. J. P., Lancelin, J. M., Carvalho, R. A., Geraldes, C. F. G.

C., and Lakhdar-Ghazal, F. (2006). Conformation study of HA(306-318) antigenic peptide of the haemagglutinin Influenza virus protein. Spectrochimica Acta Part A 65, 711-718. 23. Correia, B. E., Loureiro-Ferreira, N., Rodrigues, J. R. and Brito, R. M. M. (2006). A

structural model of an amyloid protofilament of Transthyretin. Protein Sci. 15, 28-32.

24. Vaz, D. C., Rodrigues, J. R., Sebald, W., Dobson, C. M. and Brito, R. M. M. (2006). Enthalpic and entropic contributions mediate the role of disulfide bonds on the conformational stability of Interleukin-4. Protein Sci. 15, 33-44.

25. Ferreira, P.G., Azevedo, P.J., Silva, C.G and Brito, R.M.M. (2006). Mining approximate motifs in time series. Lecture Notes in Artificial Intelligence 4265, 89-101.

26. Silva, C.G., Ostropytskyy, V., Loureiro-Ferreira, N., Swain, M., Berrar, D., Dubitzky, W., and Brito, R.M.M. (2006). P-found: The Protein Folding and Unfolding Simulation Repository. Proceedings of the 2006 IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology - CIBCB06.