Disciplinas Regulares

Regular Disciplines

Coordination: Ana Maria Moura da Silva, Denise Vilarinho Tambourgi,Sandra Coccuzzo Sampaio Vessoni,

Workload:78

Credit: 5

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This discipline presents fundamental concepts of toxinology, addressing the origin of toxins, mechanisms of action and effects on victims of accidents with venomous animals. Basic notions for deepening in optional disciplines: poisons and toxins, venomous animals and poisonings. Program Content: 1- Natural history of the main groups of venomous animals: Evolution, Ecology, Classification; 2- Poisoning by venomous animals, Clinical symptoms of poisoning by animals of medical importance, Therapeutic approaches; 3- Toxins and biological systems: Neurotoxins, Toxins affecting hemostasis, Toxins and inflammatory response, Cytotoxins; 4 - Seminars.

Bibliography:
1- Animais peçonhentos no Brasil: Biologia, clínica e terapêutica dos acidentes. Cardoso et al., São Paulo, Sarvier, 2003, 1ª. Ed. 2- Handbook of Clinical Toxicology of Animal Venoms and Poisons. Jurg Meier, Julian White. 3- Handbook of animal toxins. R. Stocklin, 2003. 4- Journal articles specialized in Toxinology and basic areas of knowledge such as biochemistry, pharmacology, immunology and cell biology, all bringing recent advances in the area.

Coordination: Roxane Maria Fontes Piazza, Luis Roberto de Camargo Gonçalves,

Workload:15

Credit: 1

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The analytical capacity is summed to the quality of the research object exposure. To stimulate scientific exchange and the collective production of knowledge, the Discipline constructs the environment of interaction: 1. It enables students to present and discuss their results and fosters the integration of students from various research lines, stimulating multidisciplinarity. 2. It encourages Doctorate students to present their project and results in English. These seminars would be an opportunity to train and improve students and to stimulate knowledge of the various areas within Toxinology. Thus, it is intended that the student present his results and scientific articles related to themes, in a clear and didactic way in the context of an updated literature. This will allow discussion of results, learning of updated methodologies, adequacy of experimental approaches and development of the critical analysis of their research project. In addition, since the Program is encouraging the internationalization of its activities, it is imperative that students, at least as a doctorate candidate, be able to present and discuss their results in English. Program content: Presentation of the projects and / or results obtained in the dissertations or thesis by the Graduate Program students, and the students of Doctorate will present in English; Discussion of the work presented.

Bibliography:
Not applicable.

Coordination: Roxane Maria Fontes Piazza,

Workload:15

Credit: 1

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To offer postgraduates lectures and mini workshops with themes relevant to the program and to Butantan Institute with invited researchers from both the Institution and from other Institutions in Brazil and abroad. Through lectures and mini workshops it is intended to broaden the knowledge of the student on various topics as well as provide an environment conducive to contact with new themes, professionals in the field, as well as stimulate the student to discuss the aspects of interest presented. Program Content: There is no specific content. The programming of the seminars and lectures is carried out by a Commission designated for this purpose that will define the line of the lectures to be realized in a certain period.

Bibliography:
Not applicable. Eventually the invited researchers provide elements of their scientific production related to the topic to be presented as a way to provide elements to deepen the discussions to be carried out in the lecture.

Coordination: Sonia Aparecida de Andrade Chudzinski,

Workload:45

Credit: 3

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Inserir os alunos de pós-graduação do programa de Toxinologia do Instituto Butantan na estruturação, criação e aplicação de aulas práticas e atividades para os olímpicos durante a fase de capacitação prática da Olimpíada Brasileira de Biologia, que é organizada por essa instituição desde 2017. Os alunos deverão participar da elaboração, planejamento e execução de propostas educativas, especialmente aulas práticas para os olímpicos classificados para a fase de capacitação prática oferecida pelo Instituto Butantan. Na capacitação as práticas oferecidas envolvem diferentes áreas da biologia e remetem as metodologias usadas pelos pós-graduandos em suas pesquisas de mestrado ou doutorado. Nessa fase, ainda são aplicadas provas e, dessa forma, os olímpicos são selecionados para a participação nas Olimpíadas Internacionais de Biologia. Serão realizadas discussões entre pesquisadores, educadores e alunos de pós-graduação acerca do planejamento das atividades, da questão e da importância das mesmas para a capacitação dos nossos jovens talentos da biologia, tanto para a participação nas Olimpíadas Internacionais de Biologia, quanto no desenvolvimento da pesquisa e inovação do país.

Bibliography:
Vida: A Ciência da Biologia: Volumes 1, 2 e 3 – Sadava - Ed. Artmed; Biologia Molecular da Célula - Alberts - Ed. Artmed; Biologia Vegetal - Raven - Ed. Guanabara Koogan; Fisiologia e Desenvolvimento Vegetal - Taiz - Ed. Artmed; Invertebrados - Brusca - Ed. Guanabara Koogan; Imunologia Celular e Molecular - Abbas - Ed. Guanabara Koogan; Farmacologia - Rang & Dale - Ed. Guanabara Koogan; Princípios de Bioquímica - Lehninger - Ed. Artmed; Introduction to Bioinformatics - Lesk - Ed. Oxford;

Coordination: Ana Leonor Abrahão Nencioni,

Workload:60

Credit: 4

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To show the neurotoxins present in poisons or other natural sources as a tool for the study of nervous structures, physiological or pathological processes as well as possible therapeutic uses. Discuss the mechanisms of action of these toxins by relating them to their applicability. Venomous, poisons and products of bacterial origin are rich sources of substances selected by nature in the course of evolution which, in addition to having their function in the life cycle of those who produce them, may have multiple applicability as a tool for studies of several biological processes. In this panorama, we highlight the neurotoxins that have been used to elucidate the structure and the functioning of the localities where they bind. In addition, several possibilities exist as therapeutic or biological control products already used and that can still be developed from the study of its mechanisms of action. Program content: Theoretical classes: 1- Toxins as a tool for the study of sodium channels; 2- Toxins as a tool for the study of potassium channels; 3 - Toxins as a tool for the study of calcium channels; 4- Therapeutic aspects of conotoxins; 5. Neurotoxins of microbial origin (botulinum and tetanum toxins) and their applications; 6- Therapeutic aspects of conotoxins; 7- Neurotoxins of microbial origin (botulinum and tetanic toxins) and their applications; 8- Convulsive neurotoxins; Anticonvulsive neurotoxins; 10- Antimicrobial and cytolytic peptides; 11- Phospholipases A2; 12- Alpha-elapidic neurotoxins and their applications; 13- Dendrotoxins; 14- Neurotoxins and the treatment of neoplasias. Seminars: 1 - Scorpion neurotoxins; 2- Spiders neurotoxins; 3- Snake neurotoxins; Conus neurotoxins; 5- Neurotoxins of microbial origin; 6- Neurotoxins and development.

Bibliography:
Arias, H. R. and Blanton, M.P., Alpha-conotoxins. Int.J.Biochem.Cell Biol. 32: 1017-1028, 2000. 2- Catterall, W.A .; Cestele, S .; Yarov-Yarovoy, V .; Yu, F. H .; Konoki, K. and Scheuer, T. Voltage-gated ion channels and gating modifier toxins. Toxicon 49: 124-141, 2007. 3- Cestele, S. and Catterall, W.A. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82: 883-892, 2000. 4- Davletov, B .; Basshrs, M. and Binz, T .. Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins. Trends Neurosci. 28: 446-452, 2005. 5- Gurevitz, M .; Karbat, I .; Cohen, L .; Ilan, N .; Kahn, R .; Turkov, M .; Stankiewicz, M .; Stuhmer, W .; Dong, K. and Gordon, D .. The insecticidal potential of scorpion beta-toxins. Toxicon 49: 473-489, 2007. 6- Harvey, A. L .; Bradley, K. N .; Cochran, S.A .; Rowan, E. G .; Pratt, J.A .; Quillfeldt, J. A. and Jerusalinsky, D. A .. What can toxins tell us for drug discovery? Toxicon 36: 1635-1640, 1998. 7- Harvey, A. L .. Twenty years of dendrotoxins. Toxicon, 39: 15-26, 2001.

Coordination: Inácio de Loiola Meirelles Junqueira de Azevedo, Solange Maria de Toledo Serrano,

Workload:60

Credit: 4

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To learn the molecular techniques currently employed in the study of toxins that are based on the investigation of cDNAs and genomes. Provide extensive knowledge about the proteomic / peptidomeric complexity of animal toxic secretions, the classes of toxins that constitute each type of toxic secretion, and the methodological approaches for its analysis. Review the main literature in the area and discuss their contributions. After decades of biochemical studies aimed at characterization of specific toxins, the spread of omic sciences (genomic, transcriptomic and proteomics) has brought new perspectives to a global understanding of venoms. The speed of information and the possibility of gene manipulation are attractive for omic sciences. Through this path, various venoms have been characterized and new toxins discovered. The transcriptomic and proteomic analyzes also allow the discovery of new toxins and / or biological or therapeutic tools. This course aims to develop a critical view of the benefits and limitations of the various experimental approaches used in the study of toxins, where the students are able to understand and use such methodologies when necessary. Program content: - Relations between Genome, Transcriptome and Proteome; - Classical methods for the analysis of transcripts and genomes; - New Generation Sequencing Platforms (NGS); - RNAseq as a tool for the discovery of toxins; - Basic bioinformatics for analysis of gene expression; - Classical methods for the isolation of proteins and peptides; - Sequencing of peptides and proteins by Edman degradation; - Basic concepts on the analysis of peptides and proteins by mass spectrometry; - Two-dimensional protein electrophoresis; - Identification of proteins by in vitro digestion with trypsin and mass spectrometry analysis; - Analysis of complex protein mixtures by trypsin digestion, two-dimensional chromatography analysis and mass spectrometry analysis; - Articles seminars on the above themes throughout the course.

Bibliography:
1- Available at the beginning of the course. 2- Bases Moleculares da Biotecnologia. H. Ulrich (Ed.). Editora Roca, São Paulo, 2008, 218p. 3- Bioquímica. D. Voet e J. G. Voet. 3ª. Edição, Artmed, 1596p. 4- Lehninger Princípios de Bioquímica. D. L. Nelson e M. M. Cox, 4ª. Edição, Sarvier, 1232p. 5- Protein Sequencing and Identification Using Tandem Mass Spectrometry. M. Kinter and N.E. Sherman (Wiley Interscience, 2000), 301p. 6- Other Molecular and Genomic Biology Books. 7- Review Articles. 8- Websites of NGS Platforms and Bioinformatics.

Coordination: Ana Marisa Chudzinski Tavassi,

Workload:60

Credit: 4

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This discipline aims to deepen students' knowledge about the mechanisms of hemostatic disorders induced by animal toxins, using a molecular approach linked to the pathophysiological systems of mammals. Animal poisons and secretions, derived from snakes, arthropods, hematophagous, induce significant changes in control of hemostasis. It is of fundamental importance to understand the mechanisms and the therapeutic action of poisonings and to identify molecules that may have therapeutic application, or to use as a biological tool for human pathologies linked to hemostasis disorders. Programmatic Content: 1- Biochemical characterization and mechanism of action of toxins or active molecules with the following action: in the coagulation system, fibrinolysis, platelet aggregation, endothelial cells, basement membrane and components of the extracellular matrix; 2- Seminars; 3- Evaluation.

Bibliography:
1- Haemostasis and Thrombosis Basic Principles and Clinical Practice. Colman,R.W. et al, Philadelphia, J.B. Lippincott Company, 2006, 5a Ed. 2- Animais peçonhentos no Brasil: Biologia, clínica e terapêutica dos acidentes. Cardoso et al., São Paulo, Sarvier, 2003, 1ª. Ed. 3- Handbook of Clinical Toxicology of Animal Venoms and Poisons: Jurg Meier, Julian White. 4- Handbook of animal toxins: R. Stocklin, 2003. 5- Selistre-de-Araujo, H. S. (Org.); Souza, D. H. F. (Org.) . Métodos em Toxinologia: Toxinas de serpentes. 1. ed. São Carlos: EDUFSCar, 2007. 1. 258p. 6- Journal articles specialized in Toxinology and basic areas of knowledge such as biochemistry, pharmacology, immunology and cell biology with recent advances of the area.

Coordination: Catarina de Fátima Pereira Teixeira, Gisele Picolo,Vanessa Olzon Zambelli,Cristina Maria Fernandes,

Workload:80

Credit: 5

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The aim of the course is to provide the student with up-to-date knowledge in the area of toxins, with emphasis on inflammatory, anti-inflammatory, nociceptive and analgesic effects, and to enhance the students’ critical capacity for using toxins as scientific tools for studies on inflammation and pain. In the last two decades, the area of toxinology has enhanced the discovery of animal toxins with important pharmacological activities, useful as scientific tools for the understanding of physiological and pathophysiological processes. On the other hand, the search for new compounds with more effective anti-inflammatory and analgesic activity and with fewer adverse effects, became intense. In this context, animal toxins represent an important source of information and are important models for the design of new therapeutic agents. The Brazilian biodiversity, still under-explored, and the formation of human resources in science, trained to investigate natural active products in the area of inflammation and pain, is of paramount importance. Program content: Theoretical lectures will be devoted to general concepts of the pathophysiology of inflammation and pain and its control, as well as the mechanisms involved in the inflammatory, nociceptive, anti-inflammatory and analgesic effects of different groups of toxins and other substances obtained from animal poisons. Theoretical classes will consist of the following topics: i) general aspects of inflammation - acute, chronic and resolution; Vascular phenomena; Cellular components and functions; Adhesion molecules and inflammatory mediators; Ii) molecular aspects of inflammation-receptors and signal transduction; Iii) general concepts about peripheral and central sensitization, nociception, hypernociception, hyperalgesia and allodynia; Iv) activation of nociceptors, chemical mediators and ion channels responsible for the transduction and transmission of nociceptive information; V) peripheral and central pain transmission channels; Vi) endogenous mechanisms of pain modulation; Vii) mode of action of analgesic and anti-inflammatory drugs; Viii) animal toxins with inflammatory activity and mechanisms of action; Ix) animal toxins with anti-inflammatory activity and mechanisms of action; X) cellular and molecular, peripheral and central mechanisms involved in pain caused by poisons / animal toxins; Xi) animal toxins with analgesic activity: mechanisms of action. Theoretical concepts will be consolidated and discussed in seminars. In addition, practical classes will be taught to show experimental models in vivo and ex vivo, for studies of inflammation and video classes for pain studies in vivo. The models for the study of inflammation will be: peritonitis, paw edema, induction of plasma extravasation (vascular permeability) and alterations of microcirculatory network and phagocytosis. For the study of pain, students will have the opportunity to know different behavioral models such as: rat paw pressure test, electronic von Frey, hot plate, tail flick, thermal hyperalgesia evaluated by Hargreaves model among others; using video classes, they will be able to follow an assay of acute hyperalgesia evaluated by the rat paw pressure test and a thermal stimulation through tail flick. From the application of these models, theeffects of toxins with activities already described will be studied.

Bibliography:
Bibliography: 1- Cells, Tissues and Disease. Eds. Majno, G.; Joris, I.. Blackwell Sci, USA, 2004. 2- Robbins Pathologic basis of disease. Eds: Cotran, R.S.; Kumar, V.; Collins, T.. 6a ed., W.B. Saunders Com., Philadelphia, USA, 2014. 3- Medzitov, R. Origin and physiological roles of inflammation. Nature 454, 428-435, 2008. 5- Sugimoto, M. A., Sousa, L. P., Pinho, V., Perretti, M., Teixeira, M. M. Resolution of inflammation: what Controls its Onset? Front. Immunol. 7: 160, 2016. 6- Serhan, C.N., Savill, J.. Resolution of inflammation: the beginning programs the end. Nature Immunol.6, 1191-1197, 2005. 7- Henson, P. M. Dampening inflammation. Nature Immunology, 6: 1179-1205, 2005. 8- Cury, Y., Oliveira-Filho, R.M., DeLucia R. Opióides In: Farmacologia Integrada.3 ed.Rio de Janeiro : Livraria e Editora RevinterLtda, v.31, p. 267- 281, 2007. 9- Deuis J R, Dvorakova L S, Vetter I. Methods Used to Evaluate Pain Behaviors in Rodents. Frontiers in Molecular Neuroscience10:284, 1-17, 2017 10- Napadow V, Sclocco R, Henderson LA. Brainstem neuroimaging of nociception and pain circuitries. Pain Rep. 7;4, e745, 2019. 11- Pennington M W, Czerwinski A, Norton R S. Peptide therapeutics from venom: Current status and potential. Bioorganic & Medicinal Chemistry 26:2738–2758, 2018. 12- Robinson SD, Undheim EAB, Ueberheide B, King GF. Venom peptides as therapeutics: advances, challenges and the future of venom-peptide discovery. Expert Rev Proteomics. 14(10):931-939, 2017. 13- Schaible, H. G.; Richter, F. Pathophysiology of pain. Langenbecks Arch. Surg., 389: 237-243, 2004. 14- Smith J E. Advances in understanding nociception and neuropathic pain. J Neurol. 265(2):231-238, 2018. 15- Wool, C.J. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann. Intern. Med. 140: 441-451, 2004.

Coordination: Luis Roberto de Camargo Gonçalves,

Workload:90

Credit: 6

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To present and discuss the pathophysiology of poisonings by opossums, arachnids and Lepidoptera, in which the symptomatology results in changes in hemostasis and / or lesions at the site of the bite. Most of venomous animals of medical importance in Brazil have poisons that induce haemostatic alterations and / or alterations at the location of the bite. Many have toxins that act on various components of the hemostatic system (coagulation, platelets, fibrinolysis, vessels, etc.) causing bleeding coagulopathies. In addition to hemostatic disorders, lesions at the site of the bite can cause serious sequelae. Serotherapy, which is efficient in reversing hemostatic disorders, does not have the same efficiency in local lesions observed in these poisonings. Thus, it is essential that specialists in toxinology have basic knowledge of the pathophysiology of experimental and / or accidental human poisoning and the efficacy of the treatment. Program content: 1- Epidemiology of accidents by venomous animals; 2 - Clinical aspects of poisoning by opossums, arachnids and lepidópteros; 3 - Normal hemostasis and actions of animal poisons in hemostasis; 4- Haemostatic alterations in accidents by venomous animals; 5- Pathophysiology of local actions induced by animal poisons; 6- Serotherapy: limitations and perspectives.

Bibliography:
1- Cardoso, J.L.C.; França, F.O.S.; Wen, F.H.; Málaque, C.M.S.; Haddad Jr., V.. Acidentes por animais peçonhentos: Biologia, clínica e terapêutica dos acidentes. São Paulo, Sarvier, 2003. 2. Scientific articles provided during the course.

Coordination: Daniel Carvalho Pimenta, Ivo Lebrun,

Workload:75

Credit: 5

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The study of peptides and their mechanisms of action have gained increasing importance due to structural advantages (synthesis and generation of analogues) and pharmacological (specificity and bioavailability) and the importance in the modulation of pathophysiological processes. Recently the possibility, non-existent before, for the large-scale production and development of new compounds for drug delivery has created the possibility of real use of these compounds as pharmaceutical prototypes and even as drugs. Therefore, the study and the understanding of the role played by these compounds as well as the understanding of the strategies for the isolation and elucidation of the structure is fundamental for the student who wishes to expand the knowledge in this area. Objectives of the course 1 - to give an overview of the importance of peptides in physiological processes and a systematic view of the different approaches in this area. 2- Study of the main families of bioactive peptides already characterized (kinins, enkephalins, endorphins, etc.) and their mechanism of action. 3 - Strategies for the isolation of peptides and definition of their structure (HPLC, FPLC, mass spectrometry and Edman degradation sequencing). 4- Types of strategies for the definition of three-dimensional structure (X-ray diffraction, circular dichroism, nuclear magnetic resonance) and peptide synthesis (solid phase solution) or molecular biology. 5- Importance of peptides in the enzymatic processes (kinetics and inhibition) and as effectors in ion channels. 6- Biological activity of peptides and definition of effects through experimental models in biological preparations. 7- Perspectives in the use of peptides as drugs. The course will be taught through lectures, seminars and eventually practical demonstrations. Program content: 1- Presentation of the course; 2 - General Aspects of the Theme; 3- Methods of purification and isolation of peptides; 4- Determination of the structure of peptides; 5- Synthesis of peptides; 6- Biological methods for the characterization of peptides; 7- Peptides as substrates or inhibitors of enzymes; 8- Main "families" of bioactive peptides and their importance in pathophysiological processes; 9- Perspectives for the use of peptides as biopharmaceuticals.

Bibliography:
1- The Pharmacological Basis of Therapeutics. Tenth Edition Goodmann & Gillman, McGraw-Hill, Biochemistry Stryer; 4th Edition; Freeman & Co. 2-Structural and mechanism in protein science -Alan Fersht; Freeman & Co. 3-Mass Spectrometry of proteins and peptides. John R. Chapman; Human Press. 4- Practical HPLC method development. Second Edition; Snyder, Kirkland, & Glajch; John Wiley & Sons, Inc. 5- Will be selected, In addition to these basic references, recent articles on the topics covered for presentation and discussion.

Coordination: Roxane Maria Fontes Piazza, Hugo Vigerelli de Barros,Claudia Trigo Pedroso de Moraes,

Workload:60

Credit: 4

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Content To review and update the molecular mechanisms of cell signaling, to study toxins that interfere with signaling, as well as to highlight the most used techniques in the area of intracellular signaling. The increasing number of intracellular systems involved in signaling shows the importance and complexity of the cellular response, such as contraction, secretion, growth, differentiation, etc. The understanding of these systems is of fundamental importance for the development of researches in the area of toxinology, to study of the mechanism of action of toxins. This study may favor the discovery of pharmacological tools important for the study of signaling as well as therapeutic agents. Program content: Understanding Receptors, Understanding Molecular Mechanisms of Intracellular Signaling, Bacterial Toxins Definition and Classification; Mechanisms and target of action; Group I toxins (superantigens and thermostable toxin); Group II toxins (cell membrane damaging toxins); Group II toxins (A / B toxins type). Toxins interfering in signaling, Techniques applied to the study of signaling; Techniques applied to detect the bacterial toxins production.

Bibliography:
1-Signal Transduction, Ed. By Heldin, CH & Purton, M, 1st edition, Published by Chapman & Hall, London, 1996. 2-Molecular Biology of the Cell, Ed. By Alberts, B. et al., 3rd edition, Garland Publishing, Inc., New York & London, 1994. 3- Cell Biology, A Laboratory Handbook, Ed. By Celis, J.E., 2nd edition, Academic Press, San Diego, 1998. 4- Signal transduction protocols, Ed. By Kendall, DA & Hill, SJ, Human Press, Totowa, 1995. 5- Handbook of Cell Signaling, Ed. By Bradshaw, RA & Dennis, EA, Academic Press, 2004, 3 volumes. 6-Guidebook to protein toxin and their use in cell biology, Ed. By Rappuoli, R & Montecucco, C, Sambrook & Tooze Publication, 1997.

Coordination: Ronaldo Zucatelli Mendonça, Geraldo Santana Magalhães,

Workload:60

Credit: 4

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Provide to students the necessary concepts to develop projects involving the expression, production and study of recombinant proteins. In order to find new molecules with potential pharmacological use, a large number of toxins of different animal species have been studied. However, a limitation in these studies is precisely the difficulty of obtaining the toxins of interest isolated and available in large quantities for tests of biological action. At present, to solve these problems, several genetic engineering techniques are used to isolate genes from different toxins and then express them in different organisms such as bacteria, yeast, insect or mammalian cells. This procedure not only guarantees a large amount of the toxin of interest, but also allows manipulation of the DNA sequence of the cloned toxin. The choice for different cell types to express recombinant toxins takes into account, among other factors, the ease of manipulation of the organism, the complexity of the molecule to be expressed and the operational cost of producing the recombinant protein. In this way, the present course aims to study the biology of the different cellular expression systems, to explore the choice of each of these systems to perform these expressions and to present methodologies of cloning and gene analysis through bioinformatics. Program Content: 1) Cells as bioreactors in the production of toxins: - prokaryotic and eukaryotic cells, - cell cultures; 2) Protein and gene expression in prokaryotic and eukaryotic cells: - structure of DNA and genetic code, - transcription and control of gene transcription, - protein translation and targeting; 3) Use of bioinformatics as a tool for gene analysis and cloning: - using databases with nucleotide and protein sequences, - searching for similarity in databases, - designing primers for PCR, - construction of multiple sequence alignment, - some useful bioinformatics resources; 4) Cloning and expression of toxins in heterologous organisms: - bacteria, - yeast, - baculovirus, - mammalian cells; 5) Analysis of recombinant expression of proteins: - analysis of mRNA expression by real-time PCR, - analysis by immunochemical methods (SDS-PAGE / Western Blot, ELISA, immunofluorescence), - biological activity analysis; 6) Structural analysis of recombinant proteins: - secondary structure (circular dichroism), - working with 3D structures of proteins, - structure and function: comparative examples between native and recombinant proteins.

Bibliography:
1- Molecular Biology of the Cell, 5th edition. Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts and Peter Walter (New York: Garland Science, 2007) - ISBN-10: 0815341059 / ISBN-13: 978-0815341055. 2- Real-Time PCR Current Technology and Applications. Julies Logan, Kirstin Edwards and Nick Saunders (Caister Academic Press- Norfolk, UK). ISBN: 978-1-904455-39-4. Gene Cloning and DNA Analysis: An Introduction 5th edition (March 3, 2006) - ISBN: 1405111216. 4- Protein Expression: a practical approach (Practical Approach Series) [Paperback]. S. J. Higgins (Editor), B. D. Hames (Editor). 5- From Genes to Cells. Stephen R. Bolsover, Jeremy S. Hyams, Steve Jones, Elizabeth A. Shephard and Hugh A. White (Wiley-Liss, 1997) - ISBN 0-47459792-9.

Coordination: Irina Kerkis, Hugo Vigerelli de Barros,

Workload:45

Credit: 3

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The objectives of the discipline are to promote modern knowledge about: a) toxins as therapeutic agents and their action in cell cultures; b) use of stem cells in drug toxinology; c) possible use of stem cells in the study of cellular and anticancer drugs from toxins; d) to use stem cells as therapeutic agents. The pharmaceutical industry has great interest in stem cell research, since these tools have become biotools for the development and testing of new drugs. Toxins from animals, on the other hand, encompass large families of biologically active polypeptides, which differ considerably from one another in terms of primary sequences, structural architecture and specifically the cellular target toxicity. Toxins constitute a very attractive source of natural molecules of great interest for the development of new biopharmaceuticals, considering nature molecular diversity. Research into the composition of a particular venom and the study of mechanism of action of a toxic individual component in its target receptor (group of cells, tissues and whole organism) contributes to the deepening and understanding of the pharmacological action of biopharmaceuticals derived from toxins. In addition, the development of new drugs from stem cells should become a reality uniting studies of pharmacology and cell biology, because the range of substances produced by stem cells in culture could open new frontiers for pharmacology. Program content: 1. Introduction. Current knowledge about stem cells. 2. Stem cells as a model for studying the toxicity of drugs. 3. Toxins: primary sequences, structural architecture and target cell toxicity 4. Toxins and stem cells as a platform for the development of new drug. 5. Stem cells as medicinal signaling agents and their therapeutic use. 6. Seminars, presentation of papers on the topics covered.

Bibliography:
1.Ulrich H et al.; 2008. Bases moleculares de biotecnologia. Ed.: ROCA, São Paulo, 1 edição, p. 217. 2. Estevan et al., 2011. Embryonic stem cells in toxicological studies. P.213-231. In: Embryonic stem cells-basic biology to bioengineering Ed .: by Michael S. Kallos, 478 pages. Publisher: InTech.http // www.intechopen.com / books / embryonic-stem-cells-basic-biology-to bioengineering / embryonic-stem-cells-in-toxicological-studies. 3. Kang KS, Trosko JE. 2011. Stem cells in toxicology: fundamental biology and practical considerations. Toxicol Sci .; 120Suppl 1: S269-89. 4. Stummann, TC and Bremer, S. 2008. The potential impact of human embryonic stem cells on safety pharmacological and toxicological assessments in drug discovery and drug development. Current Stem Cell Research & Therapy, 3 (2): 117-130 (Annex 1). 5. Caplan AI. 2009. Why are MSCs therapeutic? New data: new insight. J. Pathol., 217 (2): 318-324. 6. Kerkis I, Silva Fde S, Pereira A, Kerkis A, Rádis-Baptista G. 2010. Biological versatility of crotamine-a cationic peptide from the venom of a South American rattlesnake. Expert Opin Investig Drugs, 19 (12) 1515-25. 7. Rádis-Baptista G. Kerkis, I. 2011. Crotamine, a small basic polypeptide myotoxin from rattlesnake venom with cell-penetrating properties. Curr Pharm Des. 17 (38): 4351-61.

Coordination: Ana Marisa Chudzinski Tavassi, Gisele Picolo,

Workload:75

Credit: 5

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Objectives: This course aims to develop students' interest in innovation processes and intellectual protection, as well as the steps for the development of innovations and entrepreneurship. Rationale: Although there is a critical mass in Brazil, with scientific conditions for the discovery, patent and development of new products in biomedical areas, there is a shortage of specialized human resources or even infrastructure for proof of concept, obeying the requirements demanded by regulators, as well as for preclinical testing. These activities are still under construction in Brazil, requiring trained personnel to perform them. This is particularly important at Butantan Institute, which has, within its mission, strong performance in the development of population health products, including serums and vaccines, and more recently, diagnostic kits and secretion-derived molecules from animals with biotechnological, pharmaceutical, veterinary, and cosmetology applications, etc. For this reason, it is necessary to train personnel at various points in the innovation and entrepreneurship chain, encompassing the understanding of its importance and the different aspects of these processes, such as intellectual protection, technology transfer, quality assurance, strategies for development of innovations, start-up creations, among others. Thus, this course, over this period, provides the core knowledge involved in the process, and involves theoretical and practical activities (brainstorming and design thinking); group discussion activities, seminar presentation and proposal writing. Program content: 1- Process of new product discovery and innovation of biological products; 2- Market intelligence; 3- Definition of patentability and patents; Role of NITs in Institutions: 4- Quality system concepts; 5- Proofs of concept and stages of development; 6- Project management; 7- Scientific entrepreneurship and statistics in the health area; 8-Seminars; 9- Evaluation

Bibliography:
Bibliography: 1- Brown, Tim. Design Thinking: Uma metodologia poderosa para decretar o fim das velhas ideias. Editora Elsevier, 2010. 2- Davidson A and Farid SS. Innovation in Biopharmaceutical Manufacture. BioProcess Internatioinal. 2014; 12 (1): 28. 3- Harvey AL. Toxins and drug Discovery. Toxicon. 2014; 92: 193-200. 4- Kinch MS. An overview of FDA- approved biologics medicines. Drug Discov Today. 2015; 20 (4): 393-8. 5- Norman, G.A.V. Drugs, Devices, and the FDA: An Overview of Approval Processes for Drugs. JACC: Basic to Translational Science. Vol. 1, n. 4, 2016. 6- Osterwalder, A. Business Model Generation: Inovação em Modelos de Negócios. Editora Alta Books, 2011. 7- Palfrey, J. “Intellectual Property Strategy”, MIT Press Essential Knowledge, 2011. 8- Schuurman J, Graus YF, Labrijn AF, Ruuls S, Parren PW. Opening the door to innovation. MAbs. 2014; 6 (4): 812-9. 9- Silva PJ, Scaibley VM, Ramos KS. Academic medical centers as innovation ecosystems to address population-omics challenges in precision medicine. J Transl Med. 2018; 6 (1): 28. 10- Talele TT, Khedkar SA, Rigby AC. Successful applications of computer aided drug Discovery: moving drugs from concept to the clinic. Curr Top Med Chem. 2010; 10 (1): 127-4. 11- Teixeira LAC, Nascimento PTS, Yu A, Chudzinski-Tavassi AM. A Technology transfer Model from Public to Private Sector in Biopharmaceutical Industry. Proceedings of PICMET’16: Technology Management for Social Innovation, 2016; pp 2887-2893. 12- Zambelli VO, Pasqualoto KF, Picolo G, Chudzinski-Tavassi AM, Cury Y. Harnessing the knowledge of animal toxins to generate drugs. Pharmacol Res. 2016;112: 30-36. Periodicity of Proposition: Biennial

Coordination: Ivo Lebrun, Joanita Lopes Fernandes da Costa,

Workload:45

Credit: 3

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Bibliography:

Coordination: Adriana Rios Lopes,

Workload:60

Credit: 4

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Objectives: To transmit the knowledge of basic Enzymology, mainly enzymes applied in physiological systems and poisoning. Justification: Enzymes are involved in all physiological processes, including the poisoning process. Therefore, knowledge of Enzymology is essential for any development in this and other areas. Program Content: 1. History of enzyme studies; 2. Enzyme classification and nomenclature; 3. Catalytic mechanisms; 4. Enzymatic kinetics: basic principles; 5. Enzymes and physiological systems: the poisoning process; 6. Enzyme application and innovation.

Bibliography:
Bibliography: Polaina, J., MacCabe, AP, 2007. Industrial enzymes: structure, function and application. Segel, I. H., 1993. Enzyme Kinetics: Behavior and analysis of rapid equilibrium and steady-state enzyme systems. Rawlings, N.D., Savlvesen, G.S., 2013. Handbook of proteolytic enzymes. Purich D. 2010. Enzyme kinetics: catalysis and control. Ulber, R., Sell, D., 2007. White Biotechnology (Advances in Biochemical Engineering / Biotechnology). Updated reviews of the subject in several journals. Proposal frequency: Biennial