1) cells and stem cell therapy

Somatic Stem Cells;
1.1 Somatic Stem Cells;
1.2 pluripotent Stem Cells;
1.3 Clinical and Clinical Studies Pre;
1.4 Stem Cell and Cell Therapy, Transfer, Dissemination and Popularization of knowledge.

2) normal and neoplastic cell differentiation:
2.1 Neoplastic Stem Cells;
2.2 Pre Clinical Studies and Clinical Oncology;
Markers Tumorais.Entre 2.3 somatic stem cells include the hematopoietic stem cells (HSC), Mesenchymal Stem Cells (MSC) Endothelial Progenitor Cells (EPC) and Neoplastic Stem Cells (CSC).

Among the pluripotent cells include embryonic stem cells and induced pluripotent stem cells (IPS). These cells will be isolated, characterized , and morphologically and functionally cultured to become objects will focus on the studies that elucidate functional properties and molecular identification mechanism and epigenetic gene involved in the induction and control of cell differentiation.

A large set of tools and methodologies dominated by the participants will be employed in these studies, including: genomic methodologies, proteomics, citogenômicas, genetics, immunology, embryology, biological and cell culture and systems biology.

These cells are also grown on a large scale to be utilizadass in preclinical studies and clínicos. Specifically for animal studies are proposing to structure a Center for Pre-Clinical Studies of a Bank of stem cells from animals in order to allow animal studies of various sizes (histricomorfs and rodents, rabbits, sheep, pigs, dogs, cattle, and primates).

This Research Center will be formed by integrating the FMVZ USP, FZEA, Primates National Center Evandro Chagas Institute of Belém – PA, and the studies of laboratory models Animals of INCTC – National Institute of Science and Technology in Stem Cells and Cell Therapy.

The transfer, dissemination and popularization of knowledge on the subject will be treated as one of the lines of research conducted by experts with a view to strengthen the ties of relationship Community-University-Enterprise.
The program will aim to create opportunities aggregation of the basic and applied sciences, involving their students in specific training and acquisition of skills in addition to leadership, focusing on the development of critical spirit necessary to think of new challenges.

Subjects:

Models  in vitro  and  in vivo  for the Study of the pathophysiology of acute leukemia

Goals:

To enable students to graduate student to critically analyze the experiments, the assumptions and leukemogenesis models available in the literature, as well as design, execute and analyze genetic manipulation models of cells and animals useful for studies on fisiopatogenênese and therapy of human acute leukemias.

Content (menu):

Theoretical class 1: Physiology of hematopoiesis

Theoretical Lecture 2: Important trasncrição factors in the regulation of hematopoiesis

Theoretical Lecture 3: chromosomal translocations and important hybrid genes in myeloid acute leukemia

Theoretical Lecture 4: Chromosomal translocations and important hybrid genes in acute lymphoblastic leukemia

Theoretical class 5: Molecular abnormalities in acute myeloid leukemia with normal karyotype

Theoretical Lesson 6: Transgenic mice, knock in and knock out

Seminar 1: Murine models of acute promyelocytic leukemia

Practical Approach 1: Extraction of DNA, RNA and proteins

Practical Approach 2: polymerase chain reaction

Seminar 2: polymerase chain reaction

Practical Approach 3: Transfection of mammalian cells using retroviral

Seminar 3: Cloning Methods, vectors and transfection

Classroom Practice 4: murine embryo manipulation

Classroom Practice 5: Test of hematopoietic colonies in methylcellulose

Practical Approach 6: In vitro assays for analysis of cell differentiation and apoptosis

Seminar 4: regulatory pathways of apoptosis

Practical class 7: Genotyping and monitoring of hematopoiesis

Practical class 8: In vitro and in vivo for cell cycle analysis

Seminar 5: Cell cycle

Cytogenomic in Hematologic Malignancies: Concepts and Applications

Objectives:

To provide students graduate concepts of organization and genome architecture, with an emphasis on recombination mechanisms leading to genomic instability. In the context methodological tools will be presented classical and molecular cytogenetics: G -banding karyotype of, by fluorescence in situ hybridization (FISH) , and Single Nucleotide Polimorphism Array (SNP-A). The ultimate goal is that students are able to understand how Cytogenomic tools contribute to the understanding of the pathophysiology of hematologic malignancies and advances in therapy.

Content (menu):

Structure of DNA, chromosomes and cell division
genomic instability
principles of classical and molecular cytogenetics: conventional karyotyping, FISH and SNP-A
cytogenetic of importance in research and clinical practice in hematological malignancies

Practical classes:

-Culture of lymphocytes and tumor cells for karyotype analysis –
analysis and chromosome karyotyping
-Hibridização fluorescent in situ
-Analysis The SNP-data

Topics in Basic and Applied Immunology to Therapy and Biotechnology

Goals:

Aims to consolidate and / or update concepts, providing integration and critical view of the current knowledge in Basic and Applied Immunology. The objective discipline achieve these goals through discussions about revisions and recent scientific papers giving priority to the issues related to innate and adaptive immunity, humoral immune mechanisms and cellular mechanisms regulating the immune response, tumor immunity, immunological mechanisms involved in various inflammatory diseases and autoimmune diseases, immunotherapy, immunology applied to biotechnology, immunological methods applied research.

Content (menu):

The course will be taught in three – week period and will consist of presentation followed seminar discussion / debates and lectures by visiting scholars on topics of current scientific literature in Basic Immunology area and Applied therapies and biotechnology, with emphasis on:
– innate immunity: induction of innate immunity, activation of cells involved, the types of patterns receptors present on cells and their ligands present on pathogen intracellular signaling resulting from activation of such receptor interactions of the innate immunity with adaptive immunity.
– humoral immunity: biology and differentiation of B lymphocytes, antigen processing and presentation by B lymphocytes, activation of B cells, B cell subtypes, functions of B cells
– cell immunity: processing and presentation of antigens to lymphocytes, biology and differentiation T lymphocytes, activated T lymphocytes, T cell subtypes, functions of T cells
– regulation of the immune response: regulatory mechanisms of humoral and cellular mechanisms of neuroendocrine regulation of the immune system, imunometabolismo.
– Immune mechanisms involved in autoimmune, inflammatory and oncological diseases; Immunological mechanisms involved in transplant; Immunological mechanisms involved in immunotherapy.
– Immunology applied to biotechnology: and immunological methods used in biotechnology research.

Techniques Gene Expression Analysis – Basic Principles and Applications.

Goals:

This course aims to introduce the students with a solid foundation in cellular and molecular biology, the basic principles and applications of functional genomics techniques aimed at analysis of gene expression and its regulation, with analysis tools freely available on the Internet (online open-source tools), enabling him to interpret their results, as well as apply them to specific problems of their research.

Content (menu):

1. Signaling pathways, gene expression and its transcriptional regulation (epigenetic factors and transcription) and post-transcriptional (microRNAs). 2. Microarrays, Next Generation Sequencing – NGS, Protein Mass Spectrometry and High-Content Screening – HCS. 3. Functional genomics techniques aimed transcriptomics (microarray, RNA-Seq, fluorescent in situ sequencing RNA – FISSEQ), epigenetic (DNA-protein interactions: chromatin immunoprecipitation – ChIP-Chip, Chip-Seq; Modifications in the DNA: Methylated DNA immunoprecipitation – MEDIP) and RNA-protein interactions (RNA Immunoprecipitation: RIP, and PAR-CLIP CLIP). 4. Basic Data and Repositories (UCSC Genome Browser, Gene Expression Omnibus – GEO, ArrayExpress, etc). 5. Analysis using supervised and unsupervised speech data. 6. Inferring transcriptional regulatory mechanisms (Promoter regions, transcription factors and ChIP data). 7. Inferring post-transcriptional regulatory mechanisms (3`UTR regions and microRNAs expression data and RIP). 8. Analysis of signaling pathways and functional interaction networks. 9. functional enrichment analysis (gene ontology). 9. Practical application of analysis to biological problems defined: Presentation and discussion of scientific study projects.
In addition, scientific studies involving the concepts and content of the discipline, will be discussed after its presentation by the students.

Mass Spectrometry Applied to the Study of Proteome

Goals:

The course aims to promote the connection between determination of macromolecular structures and biological functions with emphasis on the application of mass spectrometry. This goal will be achieved through the presentation and discussion of review articles and seminars on scientific studies with proven relevance and impact on mass spectrometry area, published in international journals. The subject matter will give students the opportunity to learn and increase their knowledge in the application of analytical methodology as well as to develop critical thinking and problem solving skills related to biopolymers structures.

Content (menu):

Themes of the current literature in the area of mass spectrometry in the structural determination of proteins / peptides, carbohydrates, glycolipids , and glycosphingolipids. Introduction to mass spectrometry, principles and applications. Types of instruments. Forms of ionization. Collection and interpretation of mass spectra and bioinformatics applied to the use of this methodology in the area of Clinical Oncology, Stem Cells and Cell Therapy.
I- GENERAL PRINCIPLES OF MASS SPECTROMETRY
Mass Spectrometry Concept
Definition of terms used in mass spectrometry
types of mass spectrometers
Ionization puts eltrospray liquid phase (ESI)
ionization on the solid phase by matrix assisted laser desoption ionization
(MALDI)
II- MS application The peptides and proteins
preparation and appropriate samples for MS
molecular weight determination of protein
molecular weight peptides Determination of
peptide fragments
dissociation inert gas induced collision (CID-MS / MS)
amino acid sequence deduction into peptides via CID-MS / MS
interpretation of mass spectra
identification database protein (Genbank Swiss-prot, etc.)
III – MODIFICATIONS oF CHARACTERIZATION posttranslational by MS
Enrichment phosphoproteins
Determination of phosphorylation sites by mass spectrometry
characterization of carbohydrates by mass spectrometry m wings
Use MS in “parent” and “neutral loss” for phosphopeptides identification and glycopeptides
IV – glycoconjugates CHARACTERIZATION AND glycolipids
chemical and enzymatic treatment for isolation of carbohydrate
profile of isolated carbohydrate proteins or lipids by MS
permethylation of carbohydrates to MS analysis
Gancliosídeos by MS and glycolipids

Advanced Methods for Molecular Biological Research

Goals:

The course aims to provide knowledge of molecular methods applied in the development of research in different areas of research.

Content (menu):

– Fundamentals in Genetics, Molecular and Cell Biology and Genetics of microorganisms
– recombinant DNA technology.
– Molecular tools: Isolation of nucleic acids from different tissues, nucleic acid amplification methods (PCR, real time PCR), DNA sequencing, next generation sequencing, single-cell genomic analysis.
– Applications in transfusion medicine (imunohemantologia and transfusion transmitted disease), cell therapy, genetic diseases and cancer.
– Biosafety and Bioethics Applied Research
– Quality Control

Embryonic Stem Cells and Induced pluripotent (iPS): Theory and Practice

Goals:

Provide the first theoretical and practical contact graduate students with the pluripotent stem cell biology.

Content (menu):

Theory: historical, fundamentals of derivation, small and large-scale cultivation, manipulation, passage, freezing, thawing, karyotyping and characterization of embryonic stem cells and iPS mice and human.
Practice: cultivation, manipulation, pass, freezing, thawing differentiation of embryonic stem cells and human iPS, morphological, by immunocytochemistry

Methodology and Scientific Communication

Goals:

Make students understand the structure of scientific methodology and communication, and the structures of the scientific documents in its various forms. Through the analysis of scientific literature documents and those prepared by the students in the classroom and at home, students will gain experience in scientific writing and the ability to criticize prepared work for themselves and others. The main emphasis will be on scientific work, but the differences between them and reports, dissertations, thesis and oral presentations will be identified and discussed. At the end of the course, each student will present a detailed account of full scientific work related to the research that he developed or developing, or planned to graduate. Lectures will be used to present the main ideas related to the information and exercises, which will be discussed in the seminars of the following week, where students will present their texts and criticize those of others. texts will be analyzed in Portuguese and English in all areas of biomedical, leaving students the choice of one of two languages ​​for the preparation of the texts.

Content (menu):

The following are the topics to be addressed in lectures, seminars and homework: scientific method; Types of scientific documents; Criteria for publication in a scientific journal. The language as a communication tool; Comparison of the structure and content of texts in particular daily, daily newspapers, weekly magazines, history books, laboratory protocols and scientific works, encyclopedias; Structure of scientific work: The scientific writing – a developed skill through exercise; The language to be used in the preparation of the document will not necessarily be the one used in the final version; scientific work of reading in terms of structure and content; Foreigners to write scientific work based on the structure; contribution of the analysis of the results to be presented – originality; Sketch work in writing, identifying the most important information; magazine choose which will be submitted work; Exercise writing.

Week 1 :

• Scientific method
• Types of scientific documents
• Criteria for publication in a scientific journal
• The language as a communication tool
• Comparison of the structure and yet texts in private journals, daily newspapers, weekly magazine, history books, laboratory protocols and scientific encyclopedias work.
• Structure of scientific work.
• The scientific writing – a skill developed through exercise
• The language to be used in the preparation of the document will not necessarily be the one used in the final version.
• scientific work of reading in terms of structure and content.
• Strategies to write scientific work based on the structure.
• contribution of the analysis of the results to be presented – originality.
• Sketch work in writing, identifying the most important information
• Identification reader.
• magazine choose which submitted work
• Exercise writing.

week 2

• Study of the structure of the papers presented in magazines
• Structure of scientific work. Interrelations between sections
• Results section (selection of the most important results – “The message”, experimenting with forms of presentation, presentation of the results: Logic vs chronological order, presentation of other results that support the message).
• Relationship with the methods section.
• Relationship with the discussion and
• Analysis of the writing exercises of the students.

week 3

• Section methods (study examples of similar work in the journal which the work will be submitted). What should be emphasized.How many details. How much documentation. Use of tables and figures captions to detail, extend and complement the information the methods section. Special considerations for “methodological work”).
• Compared with the results section.
• Relationship with the discussion.
• Relationship with aINTRODUCTION
• Analysis of the writing exercises of the students.

week 4

Introduction – Examples of study similar work in the journal which the work will be submitted. Reading and organization of information in the literature. Definition of the issue to which the research was directed. Identification of the contribution of the research. The use of review articles eliminates the need to quote Louis Pasteur and Emil Fisher. Setting the magazine reader.

Discussion – Emphasize the most important results, without mention summarize or not relevant results. Identify the originality of its results. Discuss the most relevant results in terms of methods.

Immunotherapy Therapies and Specific Target in Cancer

Goals:

Introduce the principles of anti-cancer therapies directed at specific molecular targets. Students will have the opportunity to review main concepts relating to therapy and immunotherapy small molecule inhibitors of specific signaling pathways in diseases of contexts in which each of these therapies or is studied and used in clinical practice. Through careful analysis of scientific papers in seminars in the classroom and at home, supervised by teachers, students will mature prior knowledge and knowledge gained during the inaugural classes of each subject (taught by teachers).

Content (menu):

The following are the topics to be addressed in lectures, seminars and home study:

Module immunotherapy:

Week 1

• Theoretical class 1: Immunological Bases Cancer
• Seminar 1: dendritic cell vaccines in non-haematological malignancies

week 2

• Seminar 2: Monoclonal Antibodies in Hematologic Malignancies
• Seminar 3: Monoclonal Antibodies in non Hematologic Neoplasms

week 3

• Seminar 4: Cell Therapy – allogeneic transplantation of hematopoietic stem cells nonmyeloablative
• Seminar 5: Cell Therapy – Infusion of Donor Lymphocytes

Small molecules module

week 4

• Lecture: Cell Signaling and Cancer
• Seminar 6: tyrosine inhibitors – Kinase in Hematological Malignancies

week 5

• Seminar 7: tyrosine inhibitors – Kinase in Hematological Malignancies No
• Seminar 8: m-TOR inhibitors

week 6

• Lecture: Cancer Cell Biology – Mitochondria and Proteasome
• Seminar 9: Therapies Mitochondrial targets

week 7

• Seminar 10: Proteasome Inhibitors
• Seminar 11: New Perspectives targets under study

Experimental Models in Oncology

Goals:

The course aims to update knowledge concerning the experimental models used in scientific development in oncology, provide methodological support for research into cancer and enable an integrated view of the process of differentiation and evolution of cancer. Promote interdisciplinary collaboration and expand translational knowledge of biological and molecular mechanisms, investigation of causal factors, risk, progression and response to treatment of cancer. Greater emphasis on elucidating the ways and present opportunities as well as challenges in cancer diagnosis, classification, prevention and treatment.

Content ( huge):

The topics will be covered in lectures, practical classes, seminars, papers and homework, with emphasis on studies of the most relevant issues and news in the cancer biology. 1.Modelos chemical and physical animal carcinogenesis.

2. experimental cancer models in genetically modified animals.

3. Methods for evaluation of factors that influence the development of cancer.

4. Models of cellular and molecular studies of the genesis, evolution and treatment of cancer.

5. Analysis and Critical methodological implementation of experimental models for the understanding of human neoplasms.

6. Mechanisms of action of risk and protective factors for cancer.

7. Validation of the experimental studies and biological principles for the treatment of cancer.

8. Molecular mechanisms of DNA damage produced by ionizing radiation / biochemical repair of DNA damage.

9. Animal models for evaluation of the radiation in different animal tissues and biological materials.

10. Factors modulating the cellular response produced by ionizing radiation.

11. Interaction of chemotherapy and radiotherapy.

12. Physical aspects of ionizing radiation. TCP / NTCP.

Preclinical tests

Goals:

Promote discussion on the feasibility of pre-clinical tests applied to animal models. To enable graduate with the procedures used in preclinical testing. Demonstrate the main results of preclinical tests.

Content:

– vivarium procedures.
– Techniques of preparation and choice of animal species as models.
– Access roads in the experimental model.
– Ethics in the use of laboratory animals.
– Pre-clinical studies. Results.

Advanced Topics in hematopoiesis and Diseases Stem Cell hematopoietic

Goals:

Discuss the cellular mechanisms to molecular control of hematopoiesis, maintenance of pluripotency and differentiation of hematopoietic stem cell.

Discussing the regulatory mechanisms of hematopoiesis that are abnormal in hematological diseases, particularly in bone marrow failure and the myeloid neoplasms.

Content (imenta):

Lectures on (1) hematopoiesis and (2) bone marrow failure. Seminars on pluripotency, hematopoietic differentiation, cellular reprogramming, Immunology hematopoiesis, niche, DNA repair, biology of telomeres, clonality in hematopoiesis, clonal evolution and neoplastic, epigenetic and research tools: Southern blot, Western blot, co-immunoprecipitation, qPCR PCR-array gene sequencing, colony forming assays, immunophenotyping

Mobile multiparameter analysis by Quantitative Microscopy

Objectives:

This course aims to make students able to plan functional cellular assays based on microscopy and quantitatively analyze the images obtained. Also aims to enable the student to interpret the results of studies of different applications of the techniques covered.

Content (menu):

1. Principles of multiparameter cell analysis (High Content Analysis): Development and optimization of cellular assays compatible with HCA (cultivation and distribution of cells, transfection, fluorescent reagents and functional assays).
2. optical and fluorescence microscopy Understanding (and confocal widefield): Properties of light (wavelength, reflection, diffraction, refraction, absorption, resolution), the human eye (rods and cones), objective lens (focal plane, aberrations spherical and chromatic magnification and field of view aperture and depth of field), and transmitted light fluorescence microscope (type of illumination, fluorescence excitation, emission filters).
3. Processing and quantification of images: digital image sensors (CCD and CMOS sensors, pixel resolution and image size, binning, intensity, dynamic range, exposure, saturation, bits, and RGB gray scales), basic image processing (digital images, arrays, intensity histograms, locations and space operations / filters, binary image segmentation).
4. Image processing using the software Fiji (ImageJ).
5. Automated image analysis using CellProfiler software (importing images and metadata capture, application of morphological tools on the images to highlight cellular features, segmentation of objects, feature extraction, data export).
6. Data analysis using the software CellProfiler Analyst (export of CellProfiler data, results visualization, assisted classification of cell types.
7. Data Analysis Using the Software KNIME (data import, data manipulation, data visualization methods aggregation and normalization, clustering methods / clustering).
8. fluorescence image acquisition using an automated microscope HCS.
9. advanced Topics in multiparameter cell analysis (High Content analysis.): Presentation and discussion of scientific papers
10. practical application the techniques of quantitative microscopy defined biological problems: Presentation and discussion of scientific study projects

Change impact of Epithelial Biology in Development Carcinomas

Goals:

Provide students with an understanding of how changes in properties of the cell and epithelial tissue are related to the development of carcinomas and adenocarcinomas.
Specific: To
provide students with information that will identify and recognize the main aspects of the normal biology of cells and epithelial tissue.
Providing the student ‘s knowledge of various examples of changes in impact molecules and pathways that control aspects of epithelial biology (polarity, adhesion, cell plasticity and dynamics of stem cells) develop carcinomas.
Provide conditions for the student to develop the ability to critically analyze the results derived from complex scientific studies and to draw appropriate conclusions based on these studies.
Provide the student with knowledge of the most current scientific approaches used to unravel changes in epithelial biology contributing to the imbalance of epithelial tissue and tumor development.

Content (menu):

The course will cover an introductory part of review of the epithelial tissue biology-five topics relating aspects of epithelial biology to the development of carcinoma / adenocarcinoma. The introductory topic will be taught by the teacher. In each of the remaining topics, there will be a review of the subject class, taught by the teacher, and two classes, taught by students, with thepresentation of recent scientific papers, examples of studies on the topic area. The content covered is as follows:
1. Introduction: review of the biology of epithelial cell and the dynamics of differentiation and renewal of epithelial tissue.
2. polarity changes of epithelial cells in the development of epithelial tumors.
3. Changes in cell communication (cell-cell, cell matrix) and in carcinogenesis epithelial tissue.
4. Role of the intracellular trafficking of vesicles in the development of epithelial malignancies.
5. Disorders dynamics of epithelial stem cells and cells of epithelial tumors.
6. Plasticity epithelial cell, epithelial-mesenchymal transition and metastasis mechanisms.

Summary of Program Disciplines