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Annex A M. PHIL PROGRAMME IN MOLECULAR”BIOLOGY, VIROLOGY and IMMUNOLOGY NATIONAL CENTRE OF EXCELLENCE IN VIROLOGY AND IMMUNOLOGY For M. Phil Degree, 24 credit hours course work +06 credit hours for one year of original research work and for Ph.D degree additional 18 credit hours course work + 30 credit hours of original research work will be required. M Phil. Semester-I Course No. Course Title Credit Hours Status MVI-800 Gen & Mol. Virology 3 Core MVI-810 Cell and Mol. Biology 3 Core MVI-930 Biosafety and Bioethics 3 Core MVI-830 Gen & Mol. Immunology 3 Core Semester –I Total Credits 12 M.Phil. Semester-II Course No. Course Title Credit Hours Status MVI-804 Bacteriophage Biology 3 Core MVI-860 Viral Pathology 3 Core MVI-850 Signal Transduction 3 Core MVI-901 Bioinformatics 3 Elective MVI-xxx Elective – II 3 Elective Semester – II Total Credits 12 M Phil. Thesis Research 6 Total Credits 30 MVI-899 List of Elective_II. Courses MVI-810 Recombinant DNA techniques MVI-820 Microbiology MVI-834 Immune Pharmacology MVI-880 Molecular & General Toxicology MVI-920 Lab. Diagnostic Techniques (3 Credit Hours) (3 Credit Hours) (3 Credit Hours) (3 Credit Hours) (3 Credit Hours) 1 Compulsory Annex B PH D COURSE WORK IN MOLECULAR”BIOLOGY, VIROLOGY and IMMUNOLOGY NATIONAL CENTRE OF EXCELLENCE IN VIROLOGY AND IMMUNOLOGY PhD. Semester-I Course No. Course Title Credit Hours Status MVI-810 Adv. in Mol. Biology 3 Core MVI-801 Adv. in Virology 3 Core MVI-xxx Elective – I 3 Elective Scientific writing and presentation skills Total Credits PhD. Semester-II Course No. Non credit course 9 Course Title Credit Hours Status MVI-851 Medical Genetics 3 Core MVI-870 Vaccinology 3 Core MVI-xxx Elective – II 3 Elective Total Credits 9 PhD Thesis Project: 30 Total Credits (excluding MPhil Credits) 48 MVI-999 Elective Courses: MVI-840 Trends in Pharmacology MVI-852 Immunogenetics MVI-861 Molecular Mechanisms of Disease MVI-910 Stem Cell Studies MVI-940 Experimental Therapeutics MVI-950 Plant viruses and diseases 2 Annex C NCVI Core Curriculum MPhil/PhD program Following is the list of course that will be initially offered in NCVI. With the induction of more students and faculty, additional course will be offered and some will be modified. The changes will be made periodically by the academic body of NCVI and sent to Academic and Examination (A & E) body of NUST for final approval. Major Courses CODE List Course Title Serial No Course Code 1 MVI-80 Virology 2 MVI-81 Molecular and Cell Biology 3 MVI-82 Microbiology 4 MVI-83 Immunology/Immune disorders 5 MVI-84 Pharmacology (Viral, Immune etc) 6 MVI-85 Medical Genetics/ Targeted Gene Therapy 7 MVI-86 Viral Pathology 8 MVI-87 Vaccinology 9 MVI-88 Metabolism/Toxicology 10 MVI-89 Biotechnology/Fermentation 11 MVI-90 Bioinformatics 12 MVI-91 Stem Cell Studies 13 MVI-92 Lab Diagnostic Techniques/Instrumentation 14 MVI-93 Biosafety/Bioethics 15 MVI-94 Experimental Therapeutics 16 MVI-95 Plant viruses and diseases Each course has further Subdivisions as listed below. 3 . Serial No MVI-80 1 Virology MVI-81 2 Molecular Biology/Cell Biology MVI-82 3 Microbiology MVI-83 4 Immunology/Immune Disorders MVI-84 5 Pharmacology (Viral, Immune etc) MVI-85 6 Course Title Course Code Medical Genetics/ Targeted Gene Therapy CODE 800 801 802 803 804 805 CODE 810 811 812 813 814 815 CODE 820 821 822 823 824 825 CODE 830 831 832 833 834 835 CODE 840 841 842 843 844 845 CODE 850 851 852 4 . CONTENTS GENERAL VIROLOGY Basic Concepts in Virology ADVANCES IN VIROLOGY MECHANISTIC VIROLOGY Bacteriophage Biology CONTENTS MOLECULAR BIOLOGY CELL BIOLOGY-I CELL BIOLOGY -II GENOMICS AND PROTEOMICS CONTENTS MOLECULAR MICROBIOLOGY_1 MOLECULAR MICROBIOLOGY_2 CONTENTS CLINICAL IMMUNOLOGY 1 CLINICAL IMMUNOLOGY 2 ANTIVIRAL IMMUNOLOGY CONTENTS PHARAMACOLOGY CONTENTS GENERAL GENETICS MEDICAL GENETICS IMMUNOGENETICS MVI-86 7 Microbial Pathology MVI-87 8 Vaccinology MVI-88 9 Metabolism/Toxicology MVI-89 10 Biotechnology/Fermentation MVI-90 11 Bioinformatics MVI-91 12 Stem Cell Studies 853 854 855 CODE 860 861 862 863 864 865 CODE 870 871 872 873 874 875 CODE 880 881 882 883 884 885 CODE 890 891 892 893 894 895 CODE 900 901 902 903 904 905 CODE 910 911 912 913 5 GENETHERAPY CONTENTS Viral Pathology Molecular Mechanisms of Disease CONTENTS VACCINOLIOGY CONTENTS MOLECULAR TOXICOLOGY CONTENTS BIOTECHNOLOGY CONTENTS BIOSTATISTICS BIOINFORMATICS CONTENTS STEM CELL STUDIES MVI-92 13 Lab Diagnostic Techniques/Instrumentation MVI-93 14 Biosafety/Bioethics MVI-94 15 Experimental Therapeutics MVI-95 16 914 915 916 CODE 920 921 922 923 924 925 CODE 930 931 932 933 934 935 CODE 940 941 942 943 944 945 CODE 950 951 Plant Viruses and Diseases 952 953 954 955 6 CONTENTS LAB DIAGNOSTICS/INSTRUMENTATION CONTENTS ISO-9007 CONTENTS EXPERIMENTAL THERAPEUTICS CONTENTS PLANT VIROLOGY STRATEGIES TO COMBACT PLANT VIRUSES MVI-800: GENERAL VIROLOGY (3 CREDIT HOURS) COURSE CONTENTS: This is an introductory level course that describes the history of virology, development of the concepts of viruses, and various biological and molecular aspects of bacterial, animal and plant viruses. The course is divided into 3 parts. COUSRE CONTENTS: 200 years of discoveries General aspects of virology Viral Classification and Structure Modes of infection Cellular Models of virus propagations Replication and pathogenesis in a comparative fashion. Host-virus interactions Transformation and oncogenesis Immunopathology Host defense mechanisms Antiviral pharmacology and applied virology Bacteriophages Plant viruses and their associated diseases What is next for Virology? MVI-800: BASIC CONCEPTS IN VIROLOGY (3 CREDIT HOURS) LEARNIG OBJECTIVES: Viral life cycle, mode of replication and infection will be discussed. Cytopathic effects of viral infection, lytic and lysogenic infection and viral gene expression and host defenses will be discussed. COURSE CONTENTS: Introduction to Bacteriophages and viruses Virus Genomes/ Viral Genetics: Linear, Circular, DNA or RNA Viral Infection: Attachment, penetration, uncoating Viral Gene Expression: Early and late gene expression Viral Replication: Lytic and latent life cycles 7 Viral Pathogenesis: Virulence, Cytopathic effects, Host responses Virus spread through insect vectors Phenotype mixing and pseuodtypes Viral Transformation Prions, Viroids and Virosoids RNA transforming viruses DNA transforming viruses Host Defense Mechanisms Apoptotic or Anti-apoptotic Viruses Immune activation Anti-Viral Pharmacology Antiviral drugs BOOKS RECOMMENDED: Lytic mode of lambda development by D. Freidman and M. Gottesman, cold spring harbor laboratory, cold spring harbor, N.Y. Single stranded DNA by R.L. Sinsheimer. Principles of Virology by S.J. Flint. Fields Virology by B. Fields Principles of Virology by Knipe. Principles of Virology by Alan J. Cann. MVI-802: ADVANCES IN VIROLOGY LEARNING OBJECTIVES: (3 CREDIT HOURS) Details of the life cycle of different classes of viruses will be thought. This course is deigned in such as way that students will be able to distinguish target specific pathways of various classes of viruses. By understanding the common factors that contribute to diseases caused by viral infections, it will help students to develop strategies to prevent or resolve such infections. COURSE CONTENTS Hepresvirues (HSV-1, HSV-2, HCMV, EBV, PRV, VZV, HSV-6, HSV-8) Retroviruses (HIV-1, HIV-2, HTLV-1, HTLV-2) Defective Retroviruses and Endogenous Retrotransposons 8 Hepatitis viruses (HAV, HBV, HCV, HDV, HEV, HGV) Entroviruses (Coxsackieviruses, Echovirus, Hepatitis A, Norwalk and Norwalk like viruses, Reovirus, and Rotavirus) Influenza and cold viruses Neurotropic viruses [lymphocytic choriomeningitis virus (LCMV) and Measles virus (MV)] Adenoviruses (Ad-1, Ad-2, Ad-6) Picornaviruses (Poliovirus, rhinovirus) Togaviruses (Rubella, Yellow fever, encephalitis) Polyoma viruses (SV40, JC, and Papilloma) Coronaviruses Parvoviruses (ssDNA) Reoviruses (dsRNA) Poxviruses Plus stranded RNA viruses vs. Negative-stranded RNA viruses Yeast viral like particles (VLPs) (Ty-1, Ty-2, Ty3) Insect viruses (Dengue, Tick born) Primate viruses (Ebola and Marburg) Avian viruses (Bird flu) BOOKS RECOMMENDED: Hepatitis B and C carrier to cancer by Sarin. Retroviruses by Coffin and John M. Human Retroviruses by Bryan R. Interaction by retroviruses and Herpes viruses by H. J. Kung. Human Papilloma viruses by D.J.McCance. Human Papilloma viruses by Clare (EDT) Davy. The coronaviridae by Stuart G. Siddenn. Molecular Biology of Hepatitis B virus by Koshy. 9 MVI-803: MECHANISTIC VIROLOGY LEARNING OBJECTIVES: (3 CREDIT HOURS) Details of the potential mechanism(s) of viral replication and transcription and translation control will be thought. This course is deigned in such as way that students will be able to design antiviral approaches that will target specific pathways of viral life cycle. COURSE CONTENTS Oncogenic viruses and potential role of oncogenes Neurotropic viruses and neurovirulence Balance between neuroprotection and immunopathogenesis Mechanism(s) of latency Packaging/Encapsidation of viral genome Mechanisms of replication of RNA viruses Mechanisms of replication of DNA viruses Control for viral RNA processing Control of RNA transport and stability Mechanism of antiviral therapy Cell to cell spread of viruses Glycobiology relevant to viral pathogenesis and control Intracellular Transport mechanism(s) of mature viral particles Signal transduction pathways perturbed by viral infection and/gene expression Cellular and animal model of virus propagation Use of viral vectors as gene therapy Development of surrogate/pseudo type models for viral genes expression LAB PRACTICALS Bacteriophage Isolation (M13, lambda, Mu) Transduction vs. transposition assay Purification of replicative forms of M13 ssDNA Viral isolation and Plaque Assay (Hepresviruses, HSV-1 and HCMV) 10 MVI-804: BACTERIPHAGE BIOLOGY (3 CREDIT HOURS) LEARNING OBJECTIVES: Historical overview of pages will be presented. The structural organization, genetics, attachment, penetration and their replication will be discussed. The bacteriophages of marine bacteria constitute the highest amount of biodiversity in nature which will be compared with terrestrial bacteriophage ecology. The use of bacteriophages as therapy to cure multi-drug resistant bacteria, for cleaning the contaminated polluted rives/garbage will be discussed COURSE CONTENTS: General properties of phages Historical overview of phages Classification of gram positive and gram negative phages Large DNA, small DNA and RNA phages Attachment and Penetration Synthesis of protein and nucleic acids Bacteriophage lysis: Mechanism and regulation Phages and transposable elements (Mu Biology) Lambda phage T3, T7 and T4 phages P1 (Cre lox) system Defective phages and phage-like objects Evolution and natural biology of phages Evolutionary conservation and relation to eukaryotic viruses Relation of bacteriophages to bacterial ecology The health value of bacteriophages (Phage Therapy) Synthetic bacteriophages Use of bacteriophages in Physics (Nano wires and electrodes) Biocide bacteriophages for environmental surfaces Bacteriophages of industrial importance Control of bacteriophage contamination 11 MVI-810: MOLECULAR BIOLOGY (3 CREDIT HOURS) LEARNING OBJECTIVES: This course will discuss basic principles of molecular biology, structures of macromolecules with emphasis on the mechanisms that dictate the fundamental processes for the transfer of DNA->RNA-> protein. COURSE CONTENTS: Structure and origin of RNA and DNA Molecular structure and organization of Genes, Genome and Chromosomes Gene Transcription Regulation of Transcription Initiation, role of GTF and TSFs DNA Replication DNA Recombination (site specific and non-homologous) RNA Processing, Nuclear Transport, and Post-Transcriptional Control Control of Translation Selection of mRNAs to be translated mRNA degradation and interference Protein activity: Post-translational modifications, activation, localization, and degradation Protein structure and function LAB PRACTICALS Nucleic Acid Biochemistry and Analysis: DNA isolation (Plasmid and Chromosomal) Agarose and Polyacrylamide Gel Electrophoresis Electrophoresis Mobility Shift Assays (EMSA) Chromatography Spectrophotometer Techniques Molecular Cloning and subcloning Vector preparation, restriction mapping Polymerase chain reaction (PCR) of a target gene Agarose gel electrophoresis of gene PCR product 12 Analysis of restriction digest, ligation into a vector Transformation to E. coli and yeast Selection and Screening, Plasmid preparation and large scale purification Southern Blot vs. Northern blot analysis DNA sequencing and Alignments-Review bioinformatics tools Protein Translation: Open Reading Frames BOOKS RECOMMENDED Molecular Biology of the Gene by Watson, J. D., T. A. Baker, S. P. Bell, A. Gann, M. Levine, and R. Losick, Eds., (2003). (5th edition) New York, Benjamin Cummings ISBN 0-8053-4635-X The Cell by Bruce Albert and Dennis Bray, (3rd Edition), Garland Publishing Inc, New York and London Gene VIII By Lewin Benjamin Eds 2004. Oxford University press, Inc, New york. Biochemistry by Victor L. Davidson, Donald B. Sittman. 3rd Edition, 1993, Harwal Publication Co. Cell and Molecular Biology by Gerald Karp.1996 John Willey and Sons, Inc. London. Genetics by Peter J. Russel. 5th Ed. 1997, Benjamin-Cummings Publishing Company. MVI-811: CELL BIOLOGY-I (3 CREDIT HOURS) LEARNING OBJECTIVES: This course is designed to help students understand workings of the cell structure and function at cellular and molecular level. In this course molecular basis of cell structure and function is discussed which will provide students a detailed account of functional physiology of the cells. COURSE CONTENTS: Introduction Cell Organization Cell Architecture Membrane Structure and Function Bio Transport Vesicular Transport Transport Signals Nuclear Transport Bio Energetic Mitochondrial Energy Conversion 13 Chloroplast Energy Conversion Cytoskeleton Cell Shape Cell Contractility Cell to cell Communication Electrochemical Signaling Synaptic and Sensory Transduction Biochemical Signaling Receptor Ligand Interactions Second Messengers Signaling Cascades Cell Cycle and Apoptosis Phases of Cell Cycle and Cell Division Regulation of Cell Growth and Death Specialized Cell Systems BOOKS RECOMMENDED: Gene VIII By Lewin Benjamin, Eds 2004. Oxford University press, Inc, New york. Molecular Biology of the Gene by Watson, J. D., T. A. Baker, S. P. Bell, A. Gann, M. Levine, and R. Losick, 5th Ed. 2003. New York, Benjamin Cummings ISBN 0-8053-4635-X Molecular Biology of the Cell by Bruce Albert and Dennis Bray, 3rd Ed. Garland Publishing Inc, New York and London. Biochemistry by Victor L. Davidson, Donald B. Sittman. 3rd Ed. 1993, Harwal Pub Co. Cell and Molecular Biology by Gerald Karp.1996 John Willey and Sons,Inc. London. MVI-812: MEMBRANE TOPOLOGY & SIGNAL TRANSDUCTION (3CREDIT HOURS) LEARNING OBJECTIVES: This course is designed to help students understand workings of the cell structure and function at cellular and molecular level that various viruses utilize in their life cycles. In this course molecular basis of cell structure and function is discussed which will provide students a detailed account of 14 functional signaling cascade physiology of the cells. Furthermore, this course will discuss the key components of the immune system at cellular and molecular level. COURSE CONTENTS: Cell Adhesion and ECM Cell adhesion molecules and protein targeting Collagen Matrix and Non-collagen Matrix Metastasis Protein sorting An overview of protein targeting Peroxisomal protein targeting Secretary protein targeting Membrane proteins Functions of cell surface receptors Post-translation modifications Golgi protein sorting Vesicular Transport Cytoskeleton and force generation Actin dynamics and Actin myosin interaction and regulation Microtubule dynamics (dynamic instability model) MAPS and microtubule motors Cilia and flagella structure and movement Pathways of intracellular signal transduction P38 MAPK, JNK, ERK pathways RAS and RAF pathways Oxidative stress and anti-stress signaling (GST, MnSOD) GTPase and their role in cancer Ion channels expression, regulation and its relations to diseases Purinergic signaling (p2X and p2Y) PKA, PKB (AKT) PKC pathways 15 JAK/STAT and TGF- /smad pathways NF- B signaling Hedgehog Wnt and Notch pathways G-Protein coupled membrane receptors signaling Steroid hormones and nuclear receptors signaling Neurotransmitters, Opioids receptors and Eicosanoids signaling Peptide hormones and growth factors signaling Feedback and crosstalk signaling network Cell Signaling and its Applications in Disease and Therapeutics CELL BIOLOGY LAB PRACTICALS Cell and Tissue Culture Membrane fractionation Transient and Stable DNA Transfections Tissue processing Immunohistochemistry Microscopy Chromatin Immunoprecipitation (01 CREDIT HOUR) BOOKS RECOMMENDED: Gene VIII By Lewin Benjamin Eds 2004. Oxford University press, Inc, New york. Molecular Biology of the Gene by Watson, J. D., T. A. Baker, S. P. Bell, A. Gann, M. Levine, and R. Losick, 5th Ed. 2003. New York, Benjamin Cummings ISBN 0-8053-4635-X The Cell by Bruce Albert and Dennis Bray, 3rd Ed. Garland Publishing Inc, New York and London. Biochemistry by Victor L. Davidson, Donald B. Sittman. 3rd Ed. 1993, Harwal Pub Co. Cell and Molecular Biology by Gerald Karp. 1996, John Willey and Sons,Inc. London. NCVI-813: GENOMICS AND PROTEOMICS 16 (3 CREDIT HOURS) LEARNING OBJECTIVES: This course aims at offering an insight into genomics and proteomics of biological systems, their diversity and various aspects as well. COURSE CONTENTS: Yeast genome as a model eukaryotic genome system Genome diversity and evolutionary time-scale Human Genome project, it implications on viral infections Quantitative genetics Linkage, crossing over and gene mapping in Prokaryotes Linkage, crossing over gene mapping in Eukaryotes Introduction to DNA microarrays Expression profiling using microarrays DNA microarray experimental design DNA microarray data analysis and interpretation Application of functional genomic research in the study of viruses Proteome analysis Techniques of proteomics Proteomes in health and viral disease Limitations and future development BOOKS RECOMMENDED Genomics, Proteomics and Bioinformatics by A. Malcolm Campbell and Laurie J. Heyer. 2002. Benjamin Cumming Publishing Company. Proteomics: From protein sequence to function by Pannington, S and M.J.Dunn. 2001. Spring Verlag. Introduction to Proteomics, Tools for the New Biology by Daniel C. Liebler. 2001. Humana Press. DNA Microarray: A molecular cloning manual by David Bowtell and Joseph Sambrook. 2003. Cold Spring Harbor Laboratory Press, New York. 17 MVI-820: MOLECULAR MICROBIOLOGY (3 CREDIT HOUR) LEARNING OBJECTIVES: This is an introductory level course that describes various biological and molecular aspects of bacteria. Our coverage will focus almost entirely on bacteria that infect humans and cause serious disease. COURSE CONTENTS: The Bacterial Cell: An introduction to the structure of the bacterial cell. Bacterial identification in the diagnostic laboratory versus taxonomy. Taxonomic characterization of bacteria. Approaches to rapid diagnosis Nutrition, Growth and Energy Metabolism: Anaerobic and aerobic metabolism. Metabolism of sugars and fatty acids Cell Envelope, spores and Macromolecular Biosynthesis: Structure and synthesis of the cell walls of gram-positive and gram negative bacteria Antibiotics - Cell Envelope: The mode of action of beta-lactate antibiotics. Antibiotics - Protein Synthesis, Nucleic Acid Synthesis and Metabolism: The mode of action of antibacterial chemotherapeutic agents. Antibiotic susceptibility testing. Genetic Exchange: The mechanisms of gene transfer in bacteria; Insertion sequences, transposable genetic elements and plasmids. Genetic Regulatory Mechanisms: The structure and transcription of bacterial genes. The molecular mechanisms that bacteria use to regulate gene activity. Inducible and repressible operons. The molecular mechanisms involved in catabolite repression and attenuation. The ways bacteria regulate enzyme activity. Enterobacteriaceae: Enterobacteriaceae, Vibrio, Campylobacter and Helicobacter Streptococci: Groups A, B and D streptococcus, pathogenesis, diagnosis. Streptococcus pneumonia and Staphylococci. Streptococcus and pneumonia, Staphylococcus infections, food poisoning, toxic shock Neisseria and Spirochetes: Syphilis, Lyme disease, leptospirosis, gonorrhea, meningitis. Anaerobes and Pseudomonas - Opportunistic Infections. Clostridia, gas-gangrene, tetanus, botulism, pseudomonads. Zoonoses: Listeria, Francisella, Brucella, Bacillus and Yersinia Plague, Anthrax, Brucellosis, Listeriosis. 18 General Aspects of Bacterial Pathogenesis: Exotoxins and endotoxins LAB PRACTICALS General Microbiological Laboratory Techniques Media preparation Identification of gram negative and positive strains Growth curves for bacteria Bacteriophage isolation Bacterial conjugation for Plasmids transfer Genetic complementation Biosafety Guidelines BOOKS RECOMMENDED Medical Microbiology & Immunology by Warren Levinson & Ernest Jawetz. 7th Ed. 2003. McGraw-Hill Publications. ISBN 0-07-122973-6. Principles of Virology, Molecular Biology, Pathogenesis, and Control by S.J. Flint, L.W. Enquist, R.M. Krug, V.R. Racaniello, and A.M. Skalka. 2nd Ed. 2000. ASM Press. Fundamental Virology edited by D.M. Knipe and P.M Howley. 4th Ed. 2001, Lippincott Williams and Wilkins. MVI-830: BASIC IMMUNOLOGY LEARNING OBJECTIVES: (3 CREDIT HOURS) This course will cover basic concepts of immunology and the mechanism by which T and B lymphocytes acquire high level of specificity. Surface molecules will be described in detail, followed by accessory and natural killer cells and human lymphocyte antigen. Autoimmunity and tolerance will also be discussed. COURSE CONTENTS: The immune system Origins of the immune system Antibody structure and function and antibody diversity Helper T cells and their activation Organs of the lymphatic system 19 T lymphocyte development and differentiation B cell lymphocyte Development and Differentiation Cell-cell interaction (T cells and Antigen presentation cells) Non specific Defense Cells (Natural Killer cells) Monocytes and Dendritic cells HLA system (genomic organization, molecule structure, class I/II alleles and antigen presentation). The complement system Innate immunity Leukocyte migration Pathological Immune mechanisms and tolerance BOOKS RECOMMENDED Introduction to Immunolgy by J.W. Kinhall, 1983, Macmillan Pub Co. Immunology by Richard A.Goldsby, Thomas j.Kindt, Barbara A. Osborne, Janis Kuby, 2005. W.H Freeman and Co. Cellular and Molecular Immunology by Abbas, 2005. Elsevier Pub Co. Color Atlas of Immunology by G.R. Burmester, A. Pezzutto, 2006. Thieme Stuttgart, New York. MVI-831: LABORATORY APPLICATIONS OF IMMUNOLOGY ( 3 CREDIT HOURS) COURSE OBJECTIVE: This course is designed to describe techniques for antibody production, antigen detection, Immunofluorescence, and Immunohistochemistry. COURSE CONTENTS Antibody production (monoclonal and polyclonal) Antigen-Antibody interaction Definitions and precipitation techniques Techniques of electrophoresis Agglutination Techniques/complement binding Reaction ELISA, RIA, and Immunoblotting Immunrofluorescence, Immunohistology Cellular Immunity 20 Cell Isolation techniques Test of T cell Functions Antigen-specific Test Assay procedure for characterizing antigen specific T cells Humoral Immunity Test for B-cell Function Molecular Biological Methods Analytical Techniques MVI-832: IMMUNE DISORERS. (3 CREDIT HOURS) LEARNING OBJECTIVES: Major human diseases attributed due to defects in immune system will be discussed and immunological mechanism that governs the onset of key human diseases will be eluded for their potential as therapeutic potential. Genes that contributes for these defects will also be studied. COURSE CONTENTS Immunodeficiencies (Sever combined immunodeficiency syndrome) Humoral and cellular Immunodeficiencies Granulocytic Deficiencies Complement Deficiencies and Defects HIV Structure and Replication Course of HIV Infection Diagnosis and Treatment of HIV Infection Hemolytic diseases and cytopenias ABO blood group system Rhesus and other blood group systems Mechanisms of hemolytic and antigen detection autoimmune diseases Drug induced hemolysis Hemolytic due to warm antibodies Hematological Diseases Acute Leukemias Overview of Lymphoma Classification 21 Hodgkin’s disease T-Cell Lymphomas B-Cell Lymphomas Plasma Cell Dyscrasias Multiple Myeloma Cryoglulinemia Amyloidsis Tumor Immunology Detection and identification of Tumor Antigens Immune Escape Mechanisms of Tumor Antigens Immunotherapeutic Strategies (I) Immunotherapeutic Strategies (II) Transplantation of Autologous Bone Marrow/Heatopoietic Stem Cells Transplantation of Allogenic bone Marrow/Hematopietic Stem Cells Clinical Aspects of Organ Transplantation MVI-833: CLINICAL IMMUNOLOGY 2 (3 CREDIT HOURS) COURSE OBJECTIVE: Major human diseases attributed due to defects in immune system will be discussed and immunological mechanism(s) that governs the onset of key human diseases will be elucidated for their therapeutic potential. COURSE CONTENTS Musculoskeletal Diseases Clinical features of Rheumatoid Arthritis Synovial Changes in Rheumatoid Arthritis Pathogenesis of Rheumatoid Arthritis Juvenile Chronic Arthritis Clinical features of Spondylarthritis Pathogenesis of Spondylarthritis Gout, Ploychondritis, and Bechet’s syndrome 22 Skin Diseases Urticaria Contact Allergies Atopic Dermatitis and Leukocytoclastic vasculities Psoriasis and Bullous Skin Diseases Gastrointestinal Diseases Atrophic Gastritis, Whipple’s disease and Sprue Chronic Inflammatory Bowl Diseases Autoimmune Liver Diseases Respiratory Diseases Bronchial Asthma and Allergic Rhinitis Sarcoidosis and Idiopathic Pulmonary Fibrosis Extrinsic Allergic alveolitis Tuberculosis Renal Diseases Immunological mechanisms Glomerulonephritis (I) Glomerulonephritis (II) and Interstitial Nephritis Metabolic Diseases Autoimmune Thyroid Diseases Diabetic Mellitus and Autoimmune Polyglandular Syndrome Heart disease Rheumatic fever, Myocarditis, and Postinfection syndrome Neurolgical Diseases Multiple Sclerosis Autoantibody-mediated Diseases Myasthenia Gravis and Lambert-Eaton syndrome Ophthalmic Diseases Anatomy and Pathogenesis Extraocular inflammations Uveitis (I) 23 Uveitis (II) and Ocular Manifestation of Systemic Disease Reproduction Immunology Reproduction immunology Gene therapy Modern approaches and tools for gene therapy JOURNALS RECOMMEDED ANNUAL REVIEW OF IMMUNOLOGY, JOURNAL OF IMMUNOLOGY, EUROPEAN JOURNAL OF IMMUNOLOGY, IMMUNOLOGY TODAY, ADVANCES IN IMMUNOLOGY, CRC CRITICAL REVIEWS IN IMMUNOLOGY and HUMAN GENE THERAPY MVI-840: PHARMOCOLOGY (Viral, Immune) Immune Pharmacology (NSAIDS) and Glucocorticoids Antimetabolites, Cyclophosphamide, Sulfasalazine, and Gold Cyclosporin A, Mycophenolate, and Leflunomide Nucleoside and non-nucleoside analogs ATP-signaling and Viral response Antiretroviral update Xenobiotic Transport defects Side effect of drugs and liver metabolism Troxacitabine in acute leukemia Varicella vaccine and fatal outcome in leukaemia MVI-850: GENERAL GENETICS (3 CRDIT HOURS) (3 CREDIT HOURS) LEARNING OBJECTIVES: Medical genetics involves any application of genetics to medical practice. The objectives of this course is to provide students with breadth and depth of knowledge to make them realize the role of genetics in medicine and why the knowledge of medical genetics is important for today’s health care facilitators and also for scientists and clinical researchers who are interested in conducting research to elucidate the genetic basis of inherited disorders whose numbers is increasing rapidly. 24 COURSE DESCRIPTION: This course includes detailed presentation of structure and function of genes, DNA analysis, chromosomes and chromosomal aberrations; gametogenesis, Mendalian versus Non-Mendelian inheritance; genomics and population genetics. COURSE CONTENTS: Medical Genetics in Perspective: Developmental genetics-basic concepts The human chromosomes The life cycle of somatic cell Meiosis Human gametogenesis and fertilization Medical relevance of mitosis and meiosis The Human Genome: Structure and Function of Genes and Chromosomes: DNA structure; A brief view The central dogma: DNA RNA Fundamentals of gene expression Structure of human chromosome Variation in gene expression and its relevance in medicine Techniques of Gene Analysis: Analysis of individual DNA and RNA sequences Methods of nucleic acid analysis In Situ Hybridization to chromosomes DNA sequence analysis Methods of protein analysis Pattern of Single-Gene Inheritance: Terminology Genetic disorders with Classical Mendelian Inheritance Autosomal recessive inheritance Pattern of autosomal dominant inheritance X-linked inheritance Protein 25 Atypical pattern of inheritance Genetic Variation in Populations: Genetic diversity in human populations Phenotypes, genotypes and gene frequencies The Hardy-Weinberg law Frequency of X-linked genes and genotypes Factors that disturb Hardy-Weinberg equilibrium DNA profiling- a practice test of Hardy-Weinberg assumptions Gene Mapping and Human Genome Project: Physical mapping of human genes Mapping human genes by linkage analysis Applications of human genome mapping The human genome project RECOMMENDED BOOKS: Essential of Genetics by William Klug, Michael Cummings. Pearson Pretice Hall 2005. Human Genetics by Ricki Lewis. McGraw Hill 2005 Genetics in Medicine: Robert Nussbauon, Roderide Mclnnes by Huntington Willard Thompson and Thompson. Saunder 2004 Medical Genetics by Lynn Jorde, John, Michael Bamshad, Raymond White. Mobsy 2003. Medical Genetics at a Glance by Dorian Pritchard, Bruce Korf. Blackwell S. Publications 2003. MVI-851: MEDICAL GENETICS (3 CREDIT HOURS) LEARNING OBJECTIVES: Emphasis is placed on the clinical application of Genetics. Such topics include genetic assessment and counseling with prenatal diagnosis; chromosomal disorders; single gene defects attributed due to viral integration; immunogenesis and cancer genetics; multifactorial disorders congenital malfunctions; population screening; prevention and control; treatment of genetic autoimmune immune diseases. Clinical Cytogenetic: Introduction to Cytogenetic Chromosomal abnormalities 26 Mendelian disorders with Cytogenetic effects Cytogenetic analysis in cancer Disorders of autosomes and sex chromosomes Principles of Molecular Diseases: Effect of mutation on protein function Mutations disrupting the functions of biologically normal proteins Hemoglobinopathies and HIV/HCV infection correlations Molecular and Biochemical Basis of Genetics: Diseases due to mutations in different classes of proteins Enzyme Defects critical for viral infection Defects in viral receptors proteins (chemokine receptors) Disorders of structural proteins Neurodegenerative disorders Pharmacogenetic diseases Genetics of Disorders with Complex Inheritance: Genetic analysis of qualitative disease traits Genetic analysis of quantitative traits Genetic mapping of complex traits Diseases with complex inheritance Cancer Genetics: Cancer as a genetic disorder Characteristics of cancer cells Genes that cause cancer-oncogenes; tumor suppressor p53, WLM, Rb, BRCC1 Genetic changes that cause some cancer-case studies Cancer prevention, diagnosis and treatment Diagnosis Strategies for Genetic Disorders: Indication for prenatal diagnosis Genetic counseling for prenatal diagnosis Methods of prenatal diagnosis Emerging technologies for prenatal diagnosis 27 Laboratory investigations Effect of prenatal diagnosis on the prevention and management of genetic diseases Population screening (neonatal screening) Overall impact of genetic disease Types of genetic diseases Current state of treatment of genetic diseases Special consideration in treating genetic diseases Treatment strategies Genetic Counseling and Risk Assessment: Genetic counseling Case management in genetic counseling Determining recurrence risks Genetics and Society: Population screening for genetic diseases Ethical issues in medical genetics Eugenic and dysgenic effects on gene techniques RECOMMENDED BOOKS: Genetics in Medicine by Robert Nussbauon, Roderide Mclnnes. Huntington Willard Thompson and Thompson. Saunder 2004. Essential of Genetics by William Klug, Michael Cummings. Pearson Pretice Hall 2005. Human Genetics by Ricki Lewis. McGraw Hill 2005. Medical Genetics by Lynn Jorde, John, Michael Bamshad, Raymond White. Mobsy 2003. Medical Genetics at a Glance by Dorian Pritchard, Bruce Korf. Blackwell S. MVI-852 IMMUNOGENETICS (3 CREDIT HOURS) INTRODUCTION Genetics of AB and TCR genes Mechanism of AB diversity Somatic recombination Somatic hypermutation 28 B-cell receptor genes T-cell receptor genes RAG genes, Knockout mice Inherited immune disorders. Hyper Sensitivity Autoimmunity Immune Suppression. MVI-860: VIRAL PATHOLOGY LEARNING OBJECTIVES: (3 CREDIT HOURS) Major objective of this course will be to understand the viral induced pathogenesis. The symptomatic of the disease and its progression into fatalities will be discussed. The molecular pathways that lead to the induction of viral induced oral hairy leukoplakia, insulin resistance, encephalitis, demyelination hemophagocytic Lymphohistiocytosis, choleostasis hemorrhagic fever, hepatic fibrosis, cirrhosis and hepatocellular Carcinoma (HCC) will be studied. COURSE CONTENTS HCV -induced hepatic fibrosis Viral induced fatty liver diseases (steatosis) Hepatocellular carcinoma (HCC) Viral induced arthrosclerosis Viral induced ascitis Viral induced insulin resistance Viral meningitis and encephalitis CMV retinitis Falvi and foliovirus induced hemorrhagic fever Antibody dependent enhancement (ADE) of Dengue Virus Oncogenic viral pathology Viral induced choleostasis HIV/EBV induced Oral Hairy Leukoplakia (OHL) Kaposi’s Sarcoma Viral induced karatitis and conjunctivitis 29 Viral induced myocarditis and inflammatory cardiomyopathy Viral induced Emphysema Virus induced autoimmune diseases Virus Induced Demyelination EBV-induced Hemophagocytic Lymphohistiocytosis MVI-870: VACCINOLIOGY (3 CREDIT HOURS) LEARNING OBJECTIVES: This course is deigned in such as way that students will be able to design vaccines and their testing in yeast and mammalian cell, eggs and various animal models. The history of vaccine, their efficacy, potential draw back/risks, impurities, cost effective, methods will be discussed. COURSE CONTENTS History of vaccines Viral proteins as potential targets for vaccine Live versus attenuated vaccines Role of multinational companies in vaccines production DNA as vaccine Peptide & Subunits vaccine Adjuvants in vaccines Population Genetic analysis: immunity to vaccine Recombinant vaccine Animal models of vaccine testing Cost-effective approaches for production of new vaccines Human testing and efficacy of vaccines: ethical issues Recommendations of the Advisory Committee on Immunization Practices (ACIP) Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions Understanding the demand and supply of popular vaccine Launching of vaccine and clinical trials Anti-rabies immunoglobulin preparation based on F(ab')2 fragments Effect of Panavir/Zanamivir on influenza A virus reproduction 30 Vaccine safety RECOMMENDED BOOKS: Recombinant vectors in vaccine development by Fred Brown. The Vaccine book by Barry R. Bloom. Vaccine S by Plotkin_Orenstein. Mass vaccine global aspect-progress and obstacles by Plotkin. Pre-clinical and Clinical development of new vaccines by Fred Brown. JOURNALS RECOMMENDED: VACCINE, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, MEDICAL MICROBIOLOGY AND IMMUNOLOGY MVI-880: MOLECULAR TOXICOLOGY (3 CREDIT HOURS) LEARNING OBJECTIVES: This course will provide a general understanding of the science of toxicology as it relates to mankind and the environment at macro and molecular levels. COUSE CONTENTS: Fundamental concepts of Toxicology Dose-response relationships Effect of and viral infection and vaccines on liver toxicity Absorption of toxicants, distribution and storage of toxicants Biotransformation and elimination of toxicants. Classes of toxins and their respective toxic effects on humans, animals and the environment. The mechanisms of toxicity, describes medical, biochemical and genetic aspects of toxicology including regulation of gene expression Regulatory Toxicology, i.e., risk assessment and the chemo dynamics of viral contaminants in the environment. COURSE CONTENTS: Part I: Basic Concepts History and Basic Principles of Toxicology Measurement of Toxicity: Toxicokinetics during viral infection Absorption, Distribution, Storage, Elimination Biotransformation: Metabolism and bioactivation of toxins 31 Part II. Various classes of Toxicants: Chemical Toxins Toxicology of gaseous pollutants Hydrocarbons Halogenated hydrocarbons Aromatic amines and N-nitroso compounds Metals Polymers Cosmatics Biochemical toxins Insecticides and pesticides Animal venoms and poisons Plant toxins Microbial toxins Food and water borne toxins Drugs and biopharmaceuticals Part III. Mechanisms of Toxicity: Organ System Toxicology Hematotoxicity Hepatotoxicity Pulmonotoxicology Nephrotoxicology Neurotoxicology Dermatotoxicology Oto-oculartoxicology Immunotoxicology Genotoxicology Carcinogenesis: DNA damage, DNA repair Toxicogenomics: Induction and regulation of gene expression by toxins Regulatory Toxicology: 32 Toxicity assays Risk Assessment Controlling health hazards Detoxification during and after viral infections Bioremediation Phytoremediation BOOKS RECOMMENDED Principles of toxicology by Williams and Roberts. 2nd Ed. A wiley Interscience publication.John wiley and sons, Inc, New york Toxicology by Hans Marquardt, Siegfried Schafer, Roger O. McClellan 1999. Academic Press Inc. London. Industrial Toxicology by Williams and Burson. 1989. John Willey and Sons.Inc. Environmental Toxicology by Sethi, Iqbal, Satake, Mido. 2nd Ed. Casarette & Doull’s Essentials of Toxicology by Curtis D.Klassen. John B. Watkins. 2003. Mc Graw Hill. Molecular Toxicology by P. David Josephy. Oxford University press. Handbook of Toxicology by Michael Derelanko and Manfred Hollinger CRC Press 2004. MVI-890: BIOTECHNOLOGY (3 CREDIT HOURS) LEARNING OBJECTIVES: This course addresses the isolation, genetic manipulation, use of organisms (commonly genetically modified) or their fermented food production, agriculture, pharmaceutical discovery and production, molecular diagnosis, vaccine production, transgenic animal formation, human gene therapy, forensic applications, microbial-base bioprocessing pharming, bioterrorism and future of biotechnology. The course will consist of three parts: COURSE CONTENTS: Approaches of biotechnology Specific applications Social issues I. APPROACHES OF BIOTECHNOLOGY: 33 Structural Genomics: Genome sequencing Protein structure determination Functional Genomics: Bioinformatics DNA microarray Proteomics ii) Modifying Protein Production and Function: Protein engineering Antisense technology II. SPECIFIC APPLICATIONS: Food Biotechnology: Viral infection in food Animals and microbes Human Health and Diagnosis: Viral diagnostics. Forensic applications Industrial Applications: Bioprocessing Microbial-based bioprocessing and Farming Biosensors for detection of viruses Recovering viral genomes and sequences Environmental Applications of virus infection: Bioremediation 34 Waste management with virus contamination Phytoremediation Biofertilizers SOCIAL ISSUES: Rights and Privileges: Intellectual property Ethical implications Risk and regulations Perception and Fears about Viruses and Biotechnology: Contrasting public and scientific perceptions of vaccines Bioterrorism and bio defense Biotechnology: The Future: Purpose and expected outcomes Technological advances in the pipeline Third world participation in vaccine and biotechnology-bridging the gap RECOMMENDED BOOKS: Understanding Biotechnology: George Acquaah, Pearson Prentice Hall (2004). MVI-900: BIOSTATISTICS LEARNING OBJECTIVES: (3 CREDIT HOURS) This course is designed for students to understand different computational biological algorithms, construct data models, use of molecular databases, use of commonly available software for the analysis of bimolecular sequences and structures in viral and cellular genes. They should be able to interpret the results, describe common post-genomic experimental technologies associated with high-throughput data production. COURSE CONTENTS: Descriptive Biostatistics Types of numerical data Data sampling methods 35 Graphical display of Data Measurement of central tendency Measurement of dispersion Probability and probability distributions Chi-Square Test T-Test Module II: Inferential Biostatistics Sampling Distributions Confidence Intervals Baye’s Theorem Hypothesis Testing Experimental Design Introduction to operating systems Basics of Linux operating system Words Processing, Spreadsheet and Presentation Skills Internet for Biologists Introduction to programming languages Introduction to perl programming language Programming skills in perl Perl applications in bioinformatics Introduction to databases COBRA – Common Object Request Broker Architecture MySQL database management system MVI-901: BIOINFORMATICS Module I: ( 3 CREDIT HOURS) Introduction to Bioinformatics Definitions of bioinformatics and related fields Objective and scope of bioinformatics Kind of data used in bioinformatics Data integration and data analysis 36 Major biological databases Module II: Sequence Alignment Pairwise Sequence Alignment Methods and tools of sequence alignment Multiple Sequence Alignment Module III: Phylogenetic Analysis Phylogenetic trees Methods of Phylogenetic analysis Methods of evaluating phylogenies Module IV: Gene Prediction Introduction Methods of gene prediction Gene prediction tools Module V: Protein Folding/Structure Protein structure and its classification Protein classification methodology and tools Protein structure databases and visualization tools Protein structure prediction Protein function prediction Module VI: Genomics and Proteomics Introduction to genomics Tools for genome analysis Approaches for Genome-wide scan Introduction to proteomics Tools for proteome analysis 37 LAB PRACTICLES: Familiarization with Linux OS Introduction to perl scripting Creating a simple bioinformatics database Accessing the publicly available databases Pair wise and multiple sequence alignment BLAST database and genome annotation An Introduction to the vector/primer design Program Protein structure prediction for known folds Protein structure prediction for unknown folds Visualization of biomolecular structures BOOKS RECOMMENDED: Fundamentals of Biostatistics by Bernard Rosner, Duxbury 2000. An Introduction to Biostatistics by Glover & Mitchell, McGrawHill 2002. Beginning of Perl for Bioinformatics by J Tisdall, O’Reilly 2002. Bioinformatics: Sequence and Genome Analysis by DW. Mount, Clod Spring Harbor 2002. Bioinformatics: Genes, Proteins & Computers by C.A. Orengo, Advanced Text 2003. Bioinformatics: A practical guide to the analysis of genes and proteins by Baxevanis & Ouellette, Wiley 2005. TUTORIAL/ PRESENTATION (2 CREDIT HOURS) SKILL ENHANCEMENT LEARNING OBJECTIVES: This is a presentation skill enhancement course, which will enable students to prepare seminar of assigned topics covering recent knowledge in the field. Evaluation will be based on the quality of the review, oral presentation and comprehension of the subject. The exact details of the activities will be described by the faculty accordingly. 38 MVI-903: RESEARCH SEMINAR. (2 CREDIT HOURS) PROPOSAL ASSIGNMENTS LEARNING OBJECTIVES: NCVI will encourage working with clinicians and/other scientists to develop translational overlaps so the field of investigation could be enhanced. This is a skill enhancement course, which will enable students to participate in to variety of activities of their choice. These will include either preparing a review in a given subject or preparing a research proposal covering recent knowledge in that field. The exact details of the activities will be described by the faculty time to time accordingly. MVI-910: STEM CELL STUDIES (3-CREDIT HOURS) This course is designed to educate students about the new concepts of stem cell research. Primary cell culture techniques, pluripotent cell isolation, dentriatic cells injection techniques will be taught. COURSE CONTENTS Hematopiotic stem cell/lineage Bone marrow transplantation Embryonic vs. Endodermal lineage. Mesenchymal vs. Neural lineage Proliferation markers Cytokines & growth factor for stem cell culture In vitro cell tracking (flowcytometry/FACS) Chemical labeling of proteins and cells Stable isotope labeling in culture medium Bead based separation systems Fluorescent and Colorimetric labeling & detection HLA-typing T-cell receptor gene transfer by lentiviral vectors in adoptive cell therapy Karyotyping. MVI-920 LAB DIAGNOSTICS/INSTRUMENTATION 39 (3 Credit hours; TO BE OFFERED) MVI-930 BIOETHICS/BIOSAFETY (3 Credit hours) LEARNING OBJECTIVES: This course will be offered into 2 parts. First part is designed to educate students about work ethics, creating a culture for dedicated research, honesty/scientific credibility, sexual harassment, clinical misconduct, patients confidently and plagiarism. Second part will deal with safe handling of key chemicals, solvents, safe acids, base, liquid nitrogen fire, viruses, bacteria and carcinogens. Proper Instrumental handling to protect oneself in case of accidents MVI-940: EXPERIMENTAL THERAPEUTICS (3 Credit hours) LEARNING OBJECTIVES: This course is designed to search for the potential approaches that will arrest the viral-induced pathogenesis and leukemia. The oxidative and anti oxidative signaling pathways that are perturbed in many viral and immune diseases will be studied. COURSE CONTENTS: Introduction Experimental drug design A virological benefit from an induction/maintenance strategy: the Forte trial Interferon: cellular executioner Therapeutic issues in HIV/HCV-coinfected patients Tumor therapy mediated by lentiviral expression of shBcl-2 and S-TRAIL Antihyperalgesic effect of a recombinant herpes virus Silymarin (milk tussle) as potential therapeutics for oxidative stress Flavinoid and Opinopid compounds as antiviral Antioxidant therapies for cancer and viral infection (SAM, NAC) Mucosal immunotherapy for alzheimer's disease with viral vectors Genetic polymorphisms in the chemokine and chemokine receptors Transition metal therapies during viral infection (zinc supplementation) Role of cyclic nucleotide phosphodiesterase inhibitors as novel therapeutic agents for the treatment of human lymphoid malignancies. PDE4 inhibitors in primary human chronic lymphocytic leukemia (B-CLL) AND-34, an SH2 domain-containing protein their role in viral diseases 40 Focal adhesion protein p130Cas and role in human breast cancer cells Hsp90, thioredoxin reductase, and other cytosolic translocation factors as therapeutics Caspase and protease inhibitors to arrest viral replication SiRNA/ShRNA and antisense approaches to arrest gene expression BOOKS RECOMMENDED: (List to be provided later) MVI-95: PLANT VIRUSES AND DISEASES (3 CREDIT HOURS) Plant Viruses and their nomenclature Sugar Cane Viruses Woody plant virus Cotton Curl Leaf virus Other Cash crop viruses Delivery of foreign genes into plants (Agro bacterium Ti based vs. shotgun approaches) Plant viruses life cycle Host interactions Spread through insect vectors Possible Antiviral approaches for Plant viruses Viroids, Virosoids. RECOMMENDED BOOKS: Interaction between plant viruses and their vectors by R T Plumb. Plant viruses and viral diseases volume XIII by Frans. Identification of plant viruses methods and experiments by Nordun. Atlas for insects and insects plant viruses by Karl. 41