Course in Biomedical Science

B.Sc. (Hons) Course in Biomedical Science

Preamble The B.Sc. (Hons) Biomedical Science was started as an interdisciplinary course at University of Delhi. The course has been very successful in terms of the career options taken up by the students after graduation over the years. The course in its annual mode prior to 2009 and in the semester mode after 2009 has been structured to reinforce the basic exposure that students get in the higher secondary school and to gradually build on this knowledge-base. The proposed syllabus has taken advantage of the credit system to gradually make the transition from simple to complex concepts relevant to the interdisciplinary nature of undergraduate program in Biomedical Science.

In structuring the course two points have been considered primarily: one the load on the student in each course is reduced in comparison to what was existing and to offer a comprehensive skill and the knowledge base for the students keeping in mind, the employability of the students. The Core courses of the first two semesters are introductory courses in organic chemistry relevant to biology, biology of the cell, the basic building units of an organism, human physiology a glimpse at the orchestrated functioning of organ systems and the basic principles of genetics as seen in nature. At the end of the second year, a student will have basic knowledge of cell biology, genetics, bioorganic chemistry, human physiology, biochemistry, medicinal chemistry, basic molecular and immunobiology. Along with this they will have hands-on training in medical lab techniques, epidemiological data analysis, tools used in forensic science and modern biology under the Skill enhancement (SE) courses. In the second year the students would build on what is introduced in the I & II semesters; for instance building on basic bioorganic chemistry the students will learn more about proteins, the work-horses of the cell running the biochemical factory. The concepts in pharmacology, toxicology, pathology and biophysics are vital to Biomedical Sciences and these are introduced in the final year of the course. In the third year the courses include more complex concepts of mechanisms of achieving regulated functioning of the biological systems, biophysical principles of biological systems, human genetics, genome organization, medical biotechnology and biochemistry and some of the recent excitement in biology and the application of bioinformatics in Biomedical Science as part of Discipline specific elective (DSE) courses along with project work. One or two papers in the final year therefore have a longer list of learning material to be drawn from different sources; however the actual length of the material for reading/teaching is minimal. This also introduces the students to resources for self-study.

The Generic elective (GE) courses are designed to give the essential exposure to the interdisciplinary nature of Biomedical Sciences. For example, biological chemistry, bioethics and biosafety, biostatistics, immunology, biotechnology, pharmacology and toxicology are combined into one paper, bioinformatics, pathophysiology combining human physiology in the context of diseases, tools and model organism in biomedical research are part of GE courses.

The syllabus before you is the joint effort of all the teachers involved in teaching Biomedical Science in University of Delhi.

COURSE STRUCTURE

SEMESTER I SEMESTER II C1 BMS-101: Biological Chemistry C3 BMS-201: Principles of Genetics C2 BMS-102: Cell and Radiation Biology C4 BMS-202: Human Physiology and Anatomy I AECC AECC 1 English/MIL Communication or EVS 2 EVS or English/MIL Communication GE1 Generic Elective GE2 Generic Elective

SEMESTER III SEMESTER IV C5 BMS-301: Biochemistry C8 BMS-401: Immunobiology C6 BMS-302: Human Physiology and Anatomy II C9 BMS-402: Molecular Biology C7 BMS-303: Medical Microbiology C10 BMS-403: Medicinal Chemistry SEC1 Skill Enhancement Course SEC2 Skill Enhancement Course GE3 Generic Elective GE4 Generic Elective

SEMESTER V SEMESTER VI C11 BMS-501: Biophysics C13 BMS-601: Human Pathology C12 BMS-502: Pharmacology C14 BMS-602: Toxicology DSE1 Discipline Specific Elective DSE3 Discipline Specific Elective DSE2 Discipline Specific Elective DSE4 Discipline Specific Elective

C: Core Courses; GE: Generic Elective; AECC: Ability Enhancement Compulsory Course; SEC: Skill Enhancement Courses; DSE: Discipline Specific Elective

GE 1-4: Generic Electives (any one per semester in semesters 1-4) BMS-G1: Basics of Immunology BMS-G2: Biosafety and Bioethics BMS-G3: Biostatistics BMS-G4: Bridging Information Technology and Biotechnology BMS-G5: Concepts in Biotechnology BMS-G6: Concepts in Medicinal Chemistry and Drug Development BMS-G7: Introduction to Bioorganic Chemistry BMS-G8: Pathological Basis of Diseases BMS-G9: Pharmacology and Toxicology BMS-G10: Tools and Model Organisms in Biomedical Research

SEC 1-2: Skill Enhancement Courses (any one per semester in semesters 3-4) BMS-S1: Methods in Epidemiological Data Analysis BMS-S2: Medical Laboratory Diagnostics (MLD) BMS-S3: Techniques for Forensic Science BMS-S4: Tools in Modern Biology

DSE 1-4: Discipline Specific Elective (any two per semester in semesters 5-6) BMS-A: Biosafety and Bioethics BMS-B: Computational Biology and Drug Design BMS-C: Genome Organization and Function BMS-D: Human Genetics BMS-E: Medical Biochemistry BMS-F: Medical Biotechnology BMS-G: Project Work (can be chosen only in semester 6)

Core Courses (Theory + Practical*)

Semester I BMS-101: Biological Chemistry BMS-102: Cell and Radiation Biology

Semester II BMS-201: Principles of Genetics BMS-202: Human Physiology and Anatomy I

Semester III BMS-301: Biochemistry BMS-302: Human Physiology and Anatomy II BMS-303: Medical Microbiology

Semester IV BMS-401: Immunobiology BMS-402: Molecular Biology BMS-403: Medicinal Chemistry

Semester V BMS-501: Biophysics BMS-502: Pharmacology

Semester VI BMS-601: Human Pathology BMS-602: Toxicology

*(Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

B.Sc. (Hons) Course in Biomedical Science I Year Semester I and II Semester I BMS 101: Biological Chemistry

Preamble: Biological Chemistry is a discipline that integrates organic chemistry and biochemistry. It aims at understanding the relevance of biological processes using the fundamental concepts of organic chemistry. This course includes basic principles of organic chemistry like concepts of acids and bases, molecular forces responsible for the activities of biomolecules, principles of stereochemistry and their importance in understanding various biomolecular reactions along with introduction to biomolecules.

THEORY Total Lectures: 48

Unit I: Aqueous solutions (06 lectures)

Water, pH and buffers, concept of pKa (titration curves of amino acids), Henderson- Hasselbach equation, buffering zone, buffer index, concept of pI and zwitter ion.

Unit II: Concept of acids and bases (04 Lectures)

Arrhenius concept, Bronsted Lowry concept, Lewis concept, the levelling effect, effect of pH on the structure of biomolecules.

Unit III: Chemical bonding and molecular forces (06 Lectures)

Introduction to ionic interactions and covalent bond, inter-molecular and intra-molecular forces, types of intermolecular forces and their characteristics: ion-dipole, dipole-dipole, dipole-induced dipole and dispersion (London) forces, hydrogen bond (intra-molecular and inter-molecular), effect of inter/intra-molecular forces on structure of different biomolecules.

Unit IV: Stereochemistry (08 Lectures)

Optical isomerism: Optical activity, specific rotation, enantiomerism, D and L designation, racemic modification, R and S sequence rules, diasteroisomers. Conformational isomers: Conformation of ethane and butane, interconversion of projection formula, cyclohexane (mono- and di-substituted), resolution, optical purity, Geometrical isomerism: Definition, nomenclature– E and Z.

Unit V: Introduction to biomolecules

(i) Carbohydrates (05 Lectures) Monosaccharides- cyclization of aldoses and ketoses, conformations, concept of mutarotation, anomers, epimers, Disaccharides- structure, reducing and non-reducing sugars. Polysaccharides- Starch, glycogen and cellulose.

(ii) Lipid (02 Lectures) Fatty acids, triacylglycerols, steroids (cholesterol).

(iii) Amino Acids (08 Lectures) Structure and classification of amino acids, ionization, chemistry of peptide bond, non- ribosomal peptide bond formation, essential and non-essential amino acids, amino acids as precursors of other bioactive compounds, zwitterion, isoelectric point, optical properties of amino acids.

Peptide conformation: Definition of a peptide, peptide unit, peptide group, bond length, cis and trans conformation, primary, secondary (alpha helix, beta sheet, beta turn, collagen helix), tertiary and quaternary structures (with examples).

(iv) Nucleotides (02 Lectures) Sugars and Bases, conformation of sugar phosphate backbone, hydrogen bonding by bases, tautomers of bases.

Unit VI: Biologically significant name reactions: (07Lectures)

Aldol (Glucogenesis), Retro-aldol (Glycocolysis), Benzoin condensation (umpolung- decarboxylation of pyruvate in the presence of TPP) Claisen condensation (Synthesis of fatty acids), Michael addition (Dehydrases), Cannizzaro (Sugar metabolism), Baeyer Villiger reaction (FAD dependent ketone synthesis), Pinacole-pinacolone rearrangement (1,2-carbon carbon shift).

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium like videos/virtual labs etc.)

SUGGESTED READINGS 1. Concise Inorganic Chemistry, 5th edition (1999), J. D. Lee; Wiley-Blackwell, ISBN-13: 9780632052936. 2. Organic Chemistry, 6th edition (1996), I L Finar; ELBS, Longman Higher Education. ISBN- 13: 978-0582305601. 3. Lehninger: Principles of Biochemistry, 5th edition (2008), David L. Nelson and Michael M. Cox; Prentice Hall Publishers, ISBN-13: 978-0321707338 4. Biochemistry, 4th edition (2003), Campbell, M. K. and Farrel, S. O. Brooks/Cole, Cengage Learning (Boston), ISBN: 0030348498. 5. An Introduction to Practical Biochemistry, 3rd edition (1987), Plummer, McGraw-Hill College; ISBN-13: 978-0070841659 6. Organic Chemistry, 6th edition (1992), R. T. Morrison and R. N. Boyd; Pearson Education. ISBN-13: 9780136436690. 7. Biochemistry, J. M. Berg, J. L. Tymoczko and L. Stryer, 6th edition (2006), W. H. Freeman and Co.,ISBN-13: 978-0716787242 8. Bioorganic Chemistry, 3rd edition (1999), Hermann Dugas; Springer Verlag. ISBN-13: 978- 0387989105

Semester I BMS 102: Cell and Radiation Biology

Preamble: Biology is essentially the study of life in all of its varied forms. Because cells are the basic unit of life, the study of cells can be considered one of the most important areas of biological research. This course will provide information about cells, including their composition, their function and cell-cycle checkpoints. The module on radiation biology will help to explore and gain insight into radiation-induced biological responses at molecular, cellular and tissue levels.

THEORY Total Lectures: 48

Unit I: The cell (02 Lectures)

Historical background, significant landmarks, cell theory, structure of prokaryotic and eukaryotic cells, mycoplasma, viruses, viroids, prions.

Unit II: Cell membrane (04 Lectures)

Functions, different models of membrane structure, types of membrane lipids, membrane proteins: types, methods to study membrane proteins (detergents, RBC ghosts), RBC membrane as a model, membrane carbohydrates, membrane asymmetry and fluidity, Lipid rafts.

Unit III: Membrane transport (05 Lectures)

Transport of small molecules: Passive transport (simple diffusion and facilitated diffusion) and active transport and their types (P, V, F and ABC transporter) with example of Na+/K+ pump. Transport of macromolecules: Endocytosis (pinocytosis, phagocytosis), exocytosis.

Unit IV: Cell organelles (14 Lectures)

Structure and functions of various organelles: A. Nucleus: Different components, nuclear envelope- its structure, pore complex, nucleo- cytoplasmic interaction (NLS and NES), nucleolus- structure and functions. B. Chromosome: Structure- centromere and telomere, types of chromosomes based on centromere. Diversity in structure and significance of polytene and lampbrush chromosomes. Mitosis and Meiosis: Different phases and their significance. C. Endoplasmic reticulum: RER- biosynthesis and processing of proteins, co- translational and post-translational transport of proteins, signal hypothesis, protein sorting. SER- detoxification, biosynthesis of membrane, carbohydrate metabolism, steroid synthesis. D. Golgi apparatus: Golgi stack (cis, trans and medial cisternae), flow of proteins through GB. Glycosylation and protein sorting. E. Lysosomes: Development of different forms of lysosomes, role in cellular digestion, lysosomal storage diseases- Hurler syndrome, Hunter syndrome, Tay-Sachs disease and Inclusion cell disease (I-cell disease). F. Peroxisomes: Assembly, functions- H2O2 metabolism, oxidation of Fatty acids. Glyoxysomes. G. Mitochondria: Detailed structure, endosymbiotic theory, its genome, and functions in brief. H. Chloroplast: Detailed structure, its genome and functions in brief.

Unit V: Cell junctions (02 Lectures)

Basics concepts of anchoring junctions, tight junctions, communication junctions (gap junction and plasmodesmata).

Unit VI: Cytoskeletal elements (04 Lectures)

Structure, assembly and functions of: A. Microtubules: Axonemal and cytoplasmic microtubules (cilia, flagella, centrioles, basal bodies). B. Microfilaments: Globular and filamentous actin. General idea about myosin. C. Intermediate filaments: Different classes.

Unit VII: Cell cycle (03 Lectures)

Different phases of cell cycle and their significance. Checkpoints and regulation of cell cycle.

Unit VIII: Overview of cell signaling (03 Lectures)

Signaling Molecules and their receptors (extracellular and intracellular),Functions of extracellular receptors, Intracellular signal transduction pathways (cAMP, cGMP, steroid hormone response element).

Unit IX: Radiation biology (11 Lectures)

A. Introduction to radiation biology: Introduction of radiations, basic concept of radioisotopes, types of radioactive decay (gamma and beta emitter), half-life.

B. Biological effects of radiation: Effects of Ionizing and non-ionizing radiation on cells. Acute, delayed and late radiation effects (with particular reference to nervous system, gastrointestinal and hematopoietic syndrome).

C. Application in biomedicine: Use of radioisotopes in biology: Autoradiography, radioisotopes in diagnosis (thyroid disorders, cancer) and therapy (radiotherapy).

D. Radiation biosafety: Precautions and safety measures in handling radioisotopes.

PRACTICALS (Any 7) (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Microscopy- Theoretical knowledge of Light and Electron microscope. 2. To study the following techniques through electron/ photomicrographs: fluorescence microscopy, autoradiography, positive staining, negative staining, freeze fracture, freeze etching shadow casting, endocytosis and phagocytosis. 3. To explain mitosis and meiosis using permanent slides. 4. Measurement of cell size using stage micrometer. 5. To cytochemically demonstrate presence of proteins in cheek cells or onion peel using mercuric bromophenol blue or fast green. 6. To cytochemically demonstrate presence of carbohydrates in cheek cells or onion peel using periodic acid Schiff‟s reagent. 7. To cytochemically demonstrate presence of DNA in cheek cells or onion peel using Feulgen reagent. 8. To study the effect of isotonic, hypotonic and hypertonic solutions on cells. 9. To prepare polytene chromosomes.

SUGGESTED READINGS 1. The Cell: A Molecular Approach, 5th edition (2009), Cooper and Hausman. Sinauer Associates, Inc. ISBN-13: 978-0878933976. 2. Cell and Molecular Biology: Concepts and Experiments, 6th edition (2009), Gerald Karp, Wiley. ISBN-978-0470483374. 3. Physical Biochemistry: Applications to Biochemistry and Molecular Biology, David Freifelder, 2nd edition (1983), W. H. Freeman and Company. ISBN: 0716714442 / 0- 7167- 1444-2. 4. An Introduction to Radiobiology, 2nd edition (1998), A. H. W. Nias, Wiley Blackwell, ISBN- 13: 978-0471975908. 5. The World of the Cell, 7th edition (2008), Becker, Kleinsmith, Hardin and Bertoni. Benjamin Cummings, ISBN-13: 978-0805393934. 6. The Cell: A Molecular Approach, 6th edition (2013), Cooper and Hausman; Sinauer Associates, Inc. ISBN-13:978-1605351551. 7. Essential Cell Biology, 7th edition (2009), Alberts, Bray, Hopkin, Johnson, Lewis, Raff, Roberts and Walter. Garland Science. ISBN-13:978-0815341291. 8. Molecular Cell Biology, 7th edition (2012), Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Amon and Scott. W. H. Freeman. ISBN-13: 978-1429234139.

Semester II BMS 201: Principles of Genetics

Preamble: Genetics having its roots in mathematics thanks to Mendel, appeals to students as one of the analytical branches of biology even in senior school. Basic concepts that are essential to understand inheritance will be taught, starting from the abstract factors to physical basis of inheritance. The course aims to communicate the pivotal role of Mendelian concepts in the development of the science of genetics and also the fact that nature is full of examples that deviate from Mendelian laws starting from linkage groups. Introduction of models and the way they have contributed to our understanding of genetics will provide a perception of how forward genetics has been used to understand the basis of continuity of information transfer that is applicable to not only to the simple life forms but also to humans. Most of the topics will be at the introductory level, which would motivate the students to understand the molecular basis of genotype to phenotype correlation.

THEORY Total Lectures: 48

Unit I: Overview of changing paradigms in genetics (02 Lectures)

A brief overview of how genetic principles took shape, leading to the concept of a blueprint of life within the cell to the physical entity of DNA. Also mention the surprises we have from the genomics such as genetic variation between individuals. There are popular videos/presentations that can be used. The purpose is to ignite the curiosity of the students.

Unit II: Concept of genetic inheritance (06 Lectures)

Concept of alleles, haploid and diploid status, phenotype and genotype. Mendel‟s laws of inheritance: dominant and recessive inheritance, test, back and reciprocal crosses with two examples each.

Unit III: Physical basis of inheritance (06 Lectures)

Chromosomal theory of inheritance, Concept of linkage and crossing over, Cytological proof of crossing over, Genetic mapping: two and three point cross over. Distinguishing recombination and complementation. Allelic interactions- dominance relationships- complete, incomplete and co-dominance, Gene-gene interaction.

Unit IV: Introduction to DNA structure and replication (04 Lectures)

Basic structure of DNA, Salient features of the double helix, Semi-conservative replication– Meselson and Stahl experiment.

Unit V: Extra nuclear inheritance (05 Lectures)

Criteria for extra nuclear inheritance, Plastid inheritance in Mirabilis jalapa, Kappa particles in Paramecium, Maternal effect- snail shell coiling, Cytoplasmic inheritance (mitochondria and chloroplast).

Unit VI: Chromosomal abnormalities (03 Lectures)

Structural abnormalities (duplication, insertion, deletion, translocation – reciprocal and non- reciprocal). Numerical abnormalities (aneuploidy and euploidy).

Unit VII: Transposable genetic elements (03 Lectures)

Prokaryotic transposable elements- IS elements, Composite transposons. Eukaryotic transposable elements- Ac-Ds system in maize. Uses of transposons.

Unit VIII: Analysis of genetic inheritance in human (06 Lectures)

Gathering family history, pedigree symbols and construction of pedigrees. Patterns of inheritance for monogenic traits and risk assessment with examples for autosomal inheritance-dominant, recessive, sex-linked inheritance, sex-limited and sex-influenced traits, mitochondrial inheritance. Prenatal diagnosis of genetic defects.

Unit IX: Genome organization and cytogenetics (05 Lectures)

Organization of Genomes in Prokaryotes and Eukaryotes, Establishing the central Dogma, Nucleosomes organization and assembly. Euchromatin, Heterochromatin- constitutive and facultative heterochromatin. Karyotyping- banding pattern and nomenclature (G and Q banding). Common syndromes due to numerical chromosome changes, common syndromes due to structural alterations (translocations, duplications, deletions).

Unit X: Introduction to chromosomal basis of sex determination (04 Lectures)

Chromosomal theory of sex determination, Mechanisms of sex determination, Environmental factors and sex determination in human and Drosophila, Barr bodies, Dosage compensation.

Unit XI: Basic population genetics (04 Lectures)

Gene pool and gene frequency, Hardy Weinberg law and its application for calculating allelic and genotypic frequencies.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Observation of wild type and mutant phenotypes in Drosophila. 2. Preparation of culture media for Drosophila and study different stages of life cycle of Drosophila. 3. Verification of Mendelian laws through Drosophila / seeds – dominant, recessive and sex- linked 4. Preparation of Barr body. 5. Karyotyping with the help of photographs (normal and abnormal karyotypes). 6. Pedigree charts of some common characters like blood group, color blindness and PTC tasting. 7. Study of polyploidy in onion root tip by colchicine treatment. 8. Demonstration of Hardy-Weinberg Law using seed simulation.

SUGGESTED READINGS 1. Principles of Genetics, 6th edition (2011), Snustad DP and Simmons MJ, John Wiley and Sons, Inc; ISBN-13: 978-0470903599 2. Human Molecular Genetics, 3rd edition (2003) by Tom Strachan and Andrew Read; Garland Science Publishers, ISBN -13: 978-0815341826. 3. Concepts of Genetics, 10th edition, (2011). William S. Klug, Michael R. Cummings, Charlotte A. Spencer, Michael A. Palladino; Pearson Education, ISBN-13: 978- 0321724120. 4. Principles of Genetics, 8th edition (2005), Gardner EJ, Simmons MJ, Snustad DP. John Wiley and Sons, Inc. ; ISBN-13: 978-9971513467. 5. An introduction to Genetic Analysis, 10th edition (2010), Griffith AJF, Miller JH, Suzuki DT, Lewontin RC, Gelbert WM., W. H. Freeman and Co. New York. ISBN-13: 978-429229432. 6. Principles of Genetics, 6th edition (1998), Robert H. Tamarin Publisher: William C Brown Pub; ISBN-13: 978-0697354624. Semester II BMS 202: Human Physiology and Anatomy-I

Preamble: The prime concern of this syllabus is to integrate the individual functions of all the cells and tissues and organs into functional whole, the human body. Since function is dependent on a structure, the curriculum lays stress on functional anatomy of the organs. It attempts to highlight the necessary bodily balances and internal bodily control so called homeostasis as well as present their abnormal function in disease. It provides a link between basic sciences and Medicine.

THEORY Total Lectures: 48

Unit I: Body organization and Integumentary system (4 lectures)

General anatomy of the body, Introduction to various kinds of body planes, cavities, their membranes, Tissues level of organization (types, origin, function & repair). Structure and functions of Human skin.

Unit II: Blood (8 lectures)

Composition and function of blood and its components: WBC, RBC, platelets. Hematopoiesis, Hemoglobin structure and function. Hemostasis and blood coagulation mechanism, blood groups and blood banking. Basic concepts about Anemia, Abnormal hemoglobin, Polycythemia, Thalassemia, Leukemia.

Unit III: Nerve physiology (7 lectures)

Resting membrane potential, Structure and function of neuron. Action potential, Electrophysiology of ion channels and conduction of nerve impulse, Synapse and its types, Synaptic Transmission, Neurotransmitters: types and function.

Unit IV: Nervous system I: Organization of nervous system (8 lectures)

Structure and function of Central nervous system, Peripheral nervous system and Autonomic nervous system (spinal and cranial nerves). Reflexes with suitable examples and reflex arch. Temperature regulation of the human body by hypothalamus. Overview of disorders associated with the nervous system.

Unit V: Nervous system II: Special senses (8 lectures)

Concept of receptors in the body: their types, structure and functional anatomy. Regulation and common disorders of the following sensations: Vision, Hearing, Taste, Smell and Touch.

Unit VI: Muscular system (8 lectures)

Functional anatomy of Muscular system, Types of muscles, Neuromuscular transmission, General and molecular mechanism of skeletal muscle excitation and contraction, Energetics of muscle contraction and characteristics of whole muscle contraction. An overview of concepts of muscle fatigue, oxygen debt, shivering/tremor and muscle degeneration. Unit VII: Skeletal system (5 lectures)

Cartilage: structure, types and function. Bones: structure, function, location and types. Process of bone formation. Joints: structure, function and types. An overview of disorders of Skeletal system.

PRACTICALS (any 8) (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Estimation of hemoglobin (Sahli‟s method) and determination of blood group. 2. Determination of bleeding time and clotting time of blood. 3. Determination of total erythrocyte count. 4. Determination of total leukocyte count. 5. Preparation of blood smears and identifying various WBC 6. To perform differential leukocyte count of blood. 7. Determination of specific gravity of blood. 8. Determination of osmotic fragility of RBC. . *9. To study different human organs and their sections through permanent histological slides T. S. of brain, spinal cord, skeletal fibres, cardiac muscles, skeletal muscles, cartilage joints and different tissues. (*Minimum 8 slides covering the systems mentioned in theory.)

SUGGESTED READINGS 1. Guyton and Hall Textbook of Medical Physiology, 11th edition (2006), J. E. Hall; W B Saunders and Company, ISBN-13: 978-1416045748. 2. Human Physiology, 9th edition (2006), Stuart I. Fox; Tata McGraw Hill, ISBN-13: 978- 0077350062. 3. Lab Manual on Blood Analysis and Medical Diagnostics, 1st edition (2012), Dr. Gayatri Prakash; S. Chand, ISBN: 81-219-3967. 4. Manual of Practical Physiology, 4th edition (2012), A. K. Jain; Arya Publication, ISBN: 8178553155. 5. Principles of Anatomy and Physiology, 13th edition (2011), Gerard J. Tortora and Bryan H. Derrickson; Wiley and Sons, ISBN-13: 978-0470565100. 6. Ganong‟s Review of Medical physiology, 24th edition (2012), K. E. Barett, S. M. Barman, S. Boitano and H. Brooks; Tata McGraw Hill, ISBN-13: 978-0071780032. 7. Textbook of Practical Physiology, 7th edition (2007), CL Ghai; Jaypee Publication, ISBN- 13: 978-8184481419.

B.Sc. (Hons) Course in Biomedical Science II Year Semester III and IV

Semester III BMS 301: Biochemistry

Preamble: This course includes metabolic pathways and their regulation, various analytical techniques used in characterization of the proteins and a detailed account of how enzymes function: their kinetics, regulation and inhibition.

THEORY Total Lectures: 48

Unit I: Metabolic Pathways and their regulation

Carbohydrate metabolism- Glycolysis, Gluconeogenesis, Tricarboxylic acid cycle and their regulation, Cori cycle, Electron transport chain, Oxidative phosphorylation, Hexose monophosphate shunt, Glycogen metabolism and its regulation. (14 Lectures)

Lipid metabolism- Mobilization of triglycerides, Metabolism of glycerol, Biosynthesis and β- oxidation of saturated fatty acids (palmitic acid) and their regulation, Ketone bodies. (04 Lectures)

Protein metabolism- General overview, Transamination, Deamination, Glucose-alanine cycle, Urea cycle and it‟s regulation, Metabolism of phenylalanine and a branched chain amino acid. (06 Lectures)

Nucleic acid metabolism-General overview, Outline of purine and pyrimidine metabolism, Gout and Lesch-Nyhan syndrome. (04 Lectures)

Unit II: Analytical methods in protein characterization (08 Lectures)

Paper and Thin-layer chromatography, Ion exchange chromatography, Gel filtration and Affinity chromatography, SDS-PAGE, IEF.

Unit III Enzymes (08 Lectures)

Introduction to enzyme, Concept of lock and key and induced fit theory, Concept of activation energy and binding energy. Enzyme kinetics: Michaelis-Menten equation and its physiological significances, Double reciprocal plots. Enzyme Inhibition: types of inhibitors of enzyme and their examples, Turnover number.

Unit IV: Coenzymes (02 Lectures)

Classification: various types, structure and function. Structure of NAD+, NADP+, FAD and FMN.

Unit V: Regulatory enzymes. (02 Lectures)

General properties of allosteric enzymes, Regulation by covalent modification, Co-operativity, Zymogens.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. To perform dialysis 2. Protein estimation by any one: Lowry‟s/Bradford method. 3. Separation of sugars/amino acids by thin layer chromatography. 4. To perform SDS-PAGE 5. Calculation of void volume of Sephadex G -25 column, using blue dextran 6. Assay of any one enzyme under optimal conditions. 7. To study the effect of temperature on the activity of enzyme. 8. To study the effect pH on the activity of enzyme.

SUGGESTED READINGS 1. Lehninger Principles of Biochemistry, 5thedition (2012), David L. Nelson and Michael M. Cox; W. H. Freeman, ISBN-13: 978-0716771081. 2. An Introduction to Practical Biochemistry, 3rd edition (1987), Plummer, McGraw-Hill College; ISBN-13: 978-0070841659. 3. Introduction to Protein Structure, 2nd edition (1999), Carl Branden and John Tooze; Garland Science, ISBN-13: 978-0815323051. 4. Principles and Techniques of Practical Biochemistry, 5thedition (2000), Keith Wilson and John Walker; Cambridge University Press, ISBN -13: 978-0521799652.

Semester III BMS 302: Human Physiology and Anatomy-II

Preamble: This syllabus is extension of the part I. The syllabus justifiably divides the body systems into two semesters to ensure complete and comprehensive knowledge of all functionalities of the body. The course curriculum therefore emphasizes on the cardiovascular, respiratory, reproductive and endocrine system and their interrelatedness. The Laboratory exercises are designed to substantiate and clarify the theoretical concepts. Most of the topics are of introductory level and would stimulate the students to understand the basic functioning of every system and the resultant unified organization thereupon.

THEORY Total Lectures: 48

Unit I: Cardiovascular system (9 lectures)

Structure and function of heart, Properties of cardiac muscle, The Cardiac Cycle, Electrocardiogram. Circulatory system: General Principles of circulation and hemo-dynamics, Cardiovascular regulatory mechanism, Lymphatic circulation and micro-circulation.

Unit II: Respiratory system (7 lectures)

Functional anatomy of the Respiratory system. Mechanisms of pulmonary ventilation, alveolar ventilation, gaseous exchange, transport of gases, respiratory and nervous control and regulation of respiration.

Unit III: Renal physiology (8 lectures)

Functional anatomy of Kidney, function and histology of nephron, Body fluid and electrolytes: their balances and imbalances. Urine formation (glomerular filtration and tubular reabsorption), renal regulation of urine volume and osmolarity, acid-base balance. Urinary bladder: structure, micturition and its regulation. Acidosis and alkalosis, basic concepts about kidney dysfunction.

Unit IV: Reproductive system (9 lectures)

Structure and function of male and female reproductive organ. Function and regulation of testicular and ovarian hormones. Gametogenesis (oogenesis and spermatogenesis), Fertilization, Implantation, Pregnancy, Parturition and Lactation. Basic concepts of male and female infertility, Menopause and various contraceptive measures.

Unit V: Endocrine system (8 lectures)

General mechanism of hormone action. Structure, function and regulation of the following glands and their secretions: Pituitary, Hypothalamus, Pineal, Thyroid, Parathyroid, Adrenal, and Pancreas. Basic concepts about hypo and hyper secretion of hormones and their diseases.

Unit VI: Gastrointestinal system (7 lectures)

Anatomy and histology of digestive tract, gastrointestinal physiology: General principles of gut motility secretion, digestion, absorption and assimilation. Gastrointestinal hormones, their formation, action and regulation. Physiological anatomy of liver, pancreas and their functions. An overview of gastrointestinal dysfunction.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Simple Reflex arc. 2. Physiological data acquisition based experiments (ECG). 3. Physiological data acquisition based experiments (EMG). 4. Physiological data acquisition based experiments (PFT). 5. To perform platelet count. 6. To determine the reticulocyte count. 7. To perform tests for sensations (taste, touch and smell.) 8. Blood Pressure recordings in humans. 9. To study various types of contraceptive (condoms, IUD‟s, oral and injectable contraceptives) 10. To study different human organs and their sections through permanent slides. T. S. of thyroid, liver, thymus, spleen, ovary, artery, vein, capillaries, testis, pancreas, esophagus, adrenal, kidney (cortex and medulla), urinary bladder, urethra, fallopian tubes, epididymis, prostate glands, lungs, trachea, bronchioles, pitutary, heart. (Minimum 8 slides covering the systems mentioned in theory.)

SUGGESTED READINGS 1. Guyton and Hall Textbook of Medical Physiology, 11th edition (2006), J. E. Hall; W B Saunders and Company, ISBN-13: 978-1416045748. 2. Human Physiology, 9th edition (2006), Stuart I. Fox; Tata McGraw Hill, ISBN-13: 9780077350062. 3. Principles of Anatomy and Physiology, 13th edition (2011), Gerard J. Tortora and Bryan H. Derrickson; Wiley and Sons, ISBN-13: 978-0470565100. 4. Lab Manual on Blood Analysis and Medical Diagnostics, 1st edition (2012), Dr. Gayatri Prakash; S. Chand, ISBN: 81-219-3967. 5. Ganong‟s Review of Medical physiology, 24th Edition (2012), K. E. Barett, S. M. Barman, S. Boitano and H. Brooks; Tata McGraw Hill, ISBN-13: 978-0071780032. 6. Textbook of Practical Physiology, 7th Edition (2007), CL Ghai; Jaypee Publication, ISBN- 13: 978-8184481419.

Semester III

BMS 303: Medical Microbiology

Preamble: The Medical Microbiology course has been formulated to impart basic and medically relevant information on the microbes. The microbial structure, growth and development, methods and role of sterilization in the context of study of microbes are included. The pathogenic microbes and the diseases caused by them are included to broaden the perspective of the subject. This course will also focus on mechanisms of microbial pathogenesis and the host response, and the scientific approaches that are used to investigate these processes. Lastly the course deals with the problem of emerging antimicrobial resistance with reference to known pathogens.

THEORY Total Lectures: 48

Unit I: Fundamental concepts (8 Lectures) a) History of microbiology with special emphasis on contribution of Louis Pasteur and Robert Koch in Medical Microbiology. b) Major divisions of life- Domains, Kingdoms, Classical and Molecular methods of assessing microbial phylogeny- molecular chronometer, Phylogenetic trees, rRNA, DNA and proteins as indicator of phylogeny. c) Requirements for microbial growth, growth factors, culture media- synthetic and complex, types of media. Obtaining Pure Cultures, Preserving Bacterial Cultures, Growth Curves and generation time, Control of microbial growth, general concept of effect of environmental factors on growth of microbes.

Unit II: Bacterial cells - fine structure and function (5 Lectures)

Size, shape and arrangement of bacterial cells, Cell membrane, Cytoplasmic matrix, Inclusion bodies (eg magnetosomes), Nucleoid, Ultrastructure of Gram +ve and Gram –ve bacterial cell wall, Pili, Capsule, Flagella and motility, Endospore.

Unit III: Microbial genetics (5 Lectures)

Mutations, Bacterial recombination: general, site specific and replicative. Bacterial plasmids fertility factor, col plasmid, bacterial conjugation (Hfr, F′, F+, F-), Transformation, Transduction- generalized and specialized.

Unit IV: Host–Pathogen relationship in the infectious diseases (3 Lectures)

Relationship between normal microbiota and host, Opportunistic microorganisms, Nosocomial infections, Development and spread of infectious disease: invasion, pathogen, parasite, pathogenicity, virulence, carriers and their types. Routes, Mechanisms of invasion and establishment of infection.

Unit V: Microbial diseases (7 Lectures)

Respiratory tract infections (Tuberculosis); Gastrointestinal tract infections, Staphylococcal food poisoning. Clinical symptoms and life cycle of Candida albicans and plasmodium.

Unit VI: Viruses, viroids, prions (5 Lectures)

General life cycle of a virus, Structure, Enveloped and un-enveloped viruses, Plaque assay, Growth curve, Classification based on genetic material. Detail study of influenza and HIV virus with curative agent. Viroids, virusoids and prions.

Unit VII Industrial microbiology (7 lectures)

Industrial microbiological processes in industry, Basic design of fermentor (Bioreactor)- continuous and discontinuous. Importance with reference to medical microbiology like vaccine development and diagnostics.

Unit VIII: Antimicrobial chemotherapy (8 Lectures)

Range of activity and mechanism of action of antibiotics-sulfa drugs, penicillin, aminoglycosides, quinolones, cyclosporine, tetracycline and macrolides, Various test for antimicrobial activity.

PRACTICALS (Any 6) (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Preparation of different media: synthetic media, Complex media-nutrient agar, Luria Agar. 2. Staining methods: Gram‟s staining, Acid fast staining (permanent slide only), Capsule staining and spore staining. 3. Study and plot the growth curve of E. coli using turbidometric method and to calculate specific growth rate and generation time. 4. To perform antibacterial testing by Kirby-Bauer method. 5. Staining and morphological characterization of Aspergillus sp., Pencillium sp. and Saccharomyces sp. 6. Demonstration of PCR based method of detection. 7. Isolation of bacteriophages (any with a non-pathogenic host) and calculation of the plaque forming units (pfu).

SUGGESTED READINGS 1. Microbiology: An Introduction, 9th edition (2008), Gerard J. Tortora, Berdell R. Funke, Christine L. Case; Benjamin Cummings. ISBN-13: 978-0321733603. 2. Prescott, Harley, and Klein's Microbiology, 8th edition, (2011), Joanne M. Willey, Linda M. Sherwood, Christopher J. Woolverton, McGraw Hill International. ISBN-13:978- 0071313674. 3. Bailey and Scott‟s Diagnostic Microbiology, 12th edition (2007), Betty A. Forbes, Daniel F. Sahm and Alice S. Weissfeld; Mosby Elsevier Publishers, ISBN-13: 978-0808923640. 4. Microbiology, 6th edition (1993), Pelczar, Chan and Krieg; McGraw Hill International, ISBN-13: 978-0070492585. 5. Brock Biology of Microorganisms, 13th edition (2010), Michael T. Madigan, John M. Martinko, David Stahl and David P. Clark, Pearsons, Benjamin Cummings, ISBN-13: 978- 0321649638. 6. Microbiology: A Laboratory Manual, 10th edition, (2013), James Cappuccino and Natalie Sherman, Benjamin Cummings. ISBN-13: 978-0321840226.

Semester IV BMS 401: Immunobiology

Preamble: The immune system distinguishes between self and foreign molecules and thus alerts and mediates protection against attack by potentially infectious organisms. Malfunctioning of the immune system leads to a number of disorders and diseases. Immunobiology is a comprehensive study of the organization and functioning of the immune system with its network of cells and molecules. Understanding the biology of the immune system is, therefore, key to developing strategies towards prevention and cure to a number of disorders and diseases that result due to interference in the functioning and regulation of the immune system. This paper covers the structure, organization, function and regulation of and by the immune system keeping the above aspects in mind.

THEORY Total Lectures: 48

Unit I: Introduction (2 Lectures)

Historical background, General concepts of the immune system, Innate and Adaptive immunity; Active and Passive immunity; Primary and Secondary immune response.

Unit II: Structure, properties and functions of the immune system (10 Lectures)

(a) Hematopoeisis, T and B lymphocyte, NK cells, Monocytes and Macrophages; Neutrophils, Eosinophils, Basophils, Mast cells and Dendritic cells, Thymus and Bone marrow, Lymph nodes, Spleen, MALT, GALT and SALT, Pattern recognition receptors. (b) Mechanisms of pathogen killing by macrophages and neutrophils. (c) Complement system: Components of the complement activation classical, alternative and lectin pathways, Biological consequence of complement activation, Methods to study complement fixation. (d) Inflammation.

Unit III: Adaptive immune response (20 Lectures)

(a) Antigens and haptens: Properties (foreignness, molecular size, heterogeneity), B and T cell epitopes, T dependent and T independent antigens. (b) Major Histocompatibility Complex: Organization of MHC and inheritance in humans, Concepts of polygeny and polymorphism with respect to MHC. (c) Antigen presenting cells, Antigen processing and presentation pathway (cytosolic and endocytic), MLRs. (d) Humoral immune response: Concepts of B cell development in bone marrow, Generation of plasma cells and memory B cells in lymphoid organs. Antibodies: Historical perspective of antibody structure, Structure, function and properties of the antibodies, Different classes and subclasses and biological activities of antibodies, Concepts of antibody diversity and class switching. (isotype, allotype and idiotype), Transport of IgA, Hybridoma technology, Monoclonal antibodies, Basic concepts of abzymes, immunotoxin, chimera, hybrid antibodies, antigen-antibody interactions. (e) Cell mediated immune response: T cell maturation in thymus, thymic selection, self MHC restriction of T cells, T cell receptor complex. T cell sub-types and their effector function. Trimolecular complex formation between APC and Naïve T cells, clonal expansion. Cytokines properties of Interferon and Interleukins (IL1, IL2, IL4). Unit IV: Immunological principles of various reactions and techniques (8 Lectures)

Affinity and Avidity, Cross reactivity, Precipitation, Agglutination, Immunodiffusion, Immunoelectrophoresis, ELISA (indirect, sandwich, competitive, chemiluminescence and ELISPOT assay), Western blotting, Immunofluorescence, Flow cytometry. Fluorescence and immunoelectron microscopy.

Unit V: Vaccines and imunotherapeutics (4 Lectures)

Types and their characteristics, Adjuvants, Overview of National Immunization Course.

Unit VI: Dysfunctions of immune system (4 Lectures)

Types of hypersensitivity, Overview of autoimmunity. Immunodeficiency disorders: Animal models of primary immunodeficiency (nude mouse and SCID mouse). Specific impaired functions in lymphoid and myeloid lineage.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. To perform immuno-diffusion by Ouchterlony method. 2. Immuno-diffusion by Mancini method 3. Analysis of the ouchterlony and Mancini method 4. To perform ELISA checkerboard experiment. 5. To perform Complement fixation assay 6. To perform Agglutination inhibition Assay 7. To perform sandwich dot ELISA. 8. To perform Widal test.

SUGGESTED READINGS

1. Immunology, 6th edition, (2006), J. Kuby et al, W.H. Freeman and Company, New York. ISBN-13: 978-1429202114. 2. Microbiology, 7th edition, (2008), Prescott, L., John Ii Harley, Donald A. Klein, McGraw Hill. ISBN-13: 978-0071102315. 3. Roitt‟s Essential Immunology, 12th edition, (2011), Wiley-Blackwell Science. ISBN-13: 978-1405196833. 4. Immunology, 8th edition, (2012), Male, D., Brostoff, J., Roth, D.B. and Roitt, I., Elseivier- Sauders. ISBN-13: 978-0323080583. 5. An Introduction to Immunology, Immunochemistry and Immunobiology, 5th edition, (1988), Barrett, James T., Mosby Company, St. Louis. ISBN-13: 978-0801605307. 6. Immunology: An Introduction, 4th edition, (1994), Tizard, I.R., Saunders College Publishing, Philadelphia. ISBN-13: 978-0030041983. Semester IV BMS 402: Molecular Biology

Preamble: The paper Molecular Biology encompasses the basic study and understanding of the execution of central dogma. The paper starts with the mechanism of DNA replication in prokaryotes and eukaryotes along with associated discerning features. Following replication are the chapters on prokaryotic and eukaryotic transcription and translation processes. Molecular biology as a field started with an in depth research and studies on prokaryotes and only recently our understanding of life processes in eukaryotes have increased considerable. Scientists have realized that despite differences, there are subtle commonalities between the two which together point towards a common ancestry of the life kingdoms. The paper also covers a unit on mutations and repair which are considered instrumental for species deviation and eventually diversity.

THEORY Total Lectures: 48

Unit I: The replication of DNA in Prokaryotes and Eukaryotes (14 Lectures)

Chemistry of DNA synthesis, Enzyme and proteins involved in DNA replication – helicase, topoisomerases, DNA polymerases, DNA ligase, primase, RNaseH, telomerase, sliding clamp, sliding clamp loader and SSBs. Mechanism of action of DNA polymerase, DNA transactions during replication - bidirectional replication, semi-conservative, discontinuous. Mechanics at the DNA replication fork: RNA priming, Initiation and termination of DNA replication (comparing prokaryotes with eukaryotes), Regulation of bacterial DNA replication, Replicating the 5‟ end of linear chromosome, Replication coupled to chromatin synthesis in Eukaryotes, Various models of DNA replication including Trombone model, D-loop (mitochondrial), Theta mode of replication, Rolling circle model, Replication of linear ds-DNA.

Denaturation and renaturation of DNA, Cot curves, Rot curves.

Unit II: The mutability and Repair of DNA (6 Lectures)

Spontaneous and induced mutations, Types of mutations- point (non-sense, miss-sense, frame shift, insertion, deletion), Use of mutants to study gene functions, Effects on the gene product- loss of the function and gain of function. Replication Errors (transitions, transversion and thymine dimer), DNA Damage (deamination, depurination and dimerization), DNA repair: Direct repair, Mismatch repair, Excision Repair, Photoreactivation, Recombination Repair, SOS response. AMES test to identify DNA damaging chemicals, Detection of mutations: CLB method and attached X method.

Unit III: Information transfer –I: Mechanism of transcription (10 Lectures)

Basic transcription apparatus, Transcription in bacteria: Initiation, elongation and termination of transcription, Promoter sequences and concept of abortive initiation, Transcription in Eukaryotes: Types of RNA polymerases, RNA polymerase II and its promoters, TBP and other transcription factors, Transcription by RNA polymerase I and III, Inhibitors of transcription- rifampicin and α-amanitin.

Unit IV: Post-transcriptional modifications (6 Lectures)

Split Genes, Concept of introns and exons, RNA splicing pathways: Spliceosomes and Self splicing introns (Group I and Group II introns), Ribozymes, Variants of splicing: alternative splicing, exon shuffling and RNA editing, Mutually exclusive splicing (example Drosophila Dscam gene), Mechanism determining the sex of Drosophila, mRNA transport.

Unit V: Information transfer-II: Mechanism of translation (12 Lectures)

Features of genetic code and exceptions in some systems, Types of RNA: Messenger RNA, Ribosomal RNA and Transfer RNA, Ribosomal structure, Charging of tRNA, amino-acyl tRNA synthetases, Proteins and factors involved in translation, Process of translation: Initiation, elongation and termination (prokaryotes and eukaryotes), Fidelity of translation, Translation-Coupled removal of defective mRNA, Protein folding, covalent modifications and targeting, Inhibitors of protein synthesis – tetracyclins, aminoglycosides, chloramphenicol and aminoglycosides.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Calculations and preparation of various stock and working solutions of molecular biology experiments (Number 2 to 8). 2. Isolation of genomic DNA from bacterial cells. 3. Fractionation of DNA by agarose gel electrophoresis. 4. Isolation of genomic DNA from blood/tissue. 5. Quantitative estimation of salmon sperm/ calf thymus DNA using colorimetric assay using Diphenylamine reagent. 6. Quantify and analyze the purity of DNA using spectrophotometer (estimating at 260 nm, 280nm and 320nm). 7. In vitro gene amplification method of Polymerase Chain Reaction (PCR): Primer designing and setting up of the reaction. 8. Native-Polyacrylamide Gel Electrophoresis for DNA

SUGGESTED READINGS 1. Molecular Biology of the Gene, 6th edition (2007), Watson, J. D., Baker T. A., Bell, S. P., Gann, A., Levine, M., and Losick, R; Benjamin Cummings Publishers, ISBN- 13: 978- 0805395921. 2. Cell and Molecular Biology: Concepts and Experiments, 7th edition (2013), Gerald Karp. ; Wiley Publishers ISBN-13:978-1118206737. 3. Molecular Cloning: A Laboratory Manual, 4th edition (2012), Michael R. Green and Joseph Sambrook; Cold Spring Harbor Laboratory Press, ISBN-13:978-1936113422. 4. The World of the Cell, 7th edition (2008), Becker, Kleinsmith, Hardin and Bertoni. Benjamin Cummings, ISBN-13:978-0805393934. 5. Molecular Biology: Principles and Practice, 1st edition (2012), Cox, Doudna and Donnell, ISBN-13: 978-0-716-7998-8. 6. DNA Replication, 2nd edition (2005), Arthur Kornberg; University Science Books ISBN-13: 978-1891389443.

Semester IV BMS 403: Medicinal Chemistry

Preamble: The course highlights the importance of Medicinal Chemistry in all our lives and the fascination of working in a field that overlaps the disciples of chemistry, biology, biochemistry, pharmacology etc. It gives brief understanding about drug-receptor interactions, lead discovery, drug design and molecular mechanism by which drug act in the body. The course emphasizes on various drug targets in the body and drug development strategies with mechanism of action of antibacterial agents and concept of drug resistance.

THEORY Total Lectures: 48

Unit I: General introduction (2 Lectures)

Definition and scope of medicinal chemistry.

Unit II: Drug target classification (14 Lectures)

Proteins as drug targets

Receptors: The receptor role, ion channels, membrane bound enzyme activation, agonist and antagonists, concept of inverse agonist, desensitization and sensitization of receptors, affinity, efficacy and potency.

Enzymes: Enzyme inhibitors (competitive, non-competitive, suicide inhibitors), medicinal use of enzyme inhibitors.

Nucleic acids as drug targets

Classes of drugs that interact with DNA: DNA intercalators (amsacrine), Groove binders (netropsin), DNA alkylators (amines: mechlorethamine; nitrosoureas: carmustine), concept of antisense therapy.

Unit III: How drug acts: Molecular aspects (8 Lectures)

Structure and functions of cell surface receptors, Signal transduction mechanism (GPCRs, Tyrosine kinase, guanylate- cyclase linked receptors and intracellular receptors that regulate DNA transcription).

Unit IV: Physicochemical principles of drug action (8 Lectures)

Partition coefficient, Drug dissolution, Acid-base properties, Surface activity, Bioavailability, Stereochemical aspects of drug action, Electronic structure (Hammet correlations) and determining relationship between chemical and biological data (Hansch approach).

Unit V: Measurement of drug effects (6 Lectures)

Kinetic analysis of ligand receptor interactions using scatchard plot, Double reciprocal plot, Hill plot, Forces involved, Relationship between dose and effect (graded and quantal response). Unit VI: Principles of drug design (6 Lectures)

Introduction to SAR, Strategies in the search for new lead compounds, Analogue synthesis versus Rational drug design, Concept of prodrugs.

Unit VII: Introduction to combinatorial synthesis (4 Lectures)

Methods of parallel synthesis, Methods in mixed combinatorial synthesis (mix and split method), Limitations of combinatorial synthesis.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Recrystallization of organic compound, determination of its melting point and TLC. 2. Preparation of Benzocaine. 3. Preparation of Benzoquinone. 4. Determination of partition coefficient of Aspirin in octanol-water system. 5. Preparation of Phenacetin. 6. Preparation of Hippuric acid. 7. Preparation of s-benzyl thiouronium salt. 8. Extraction of caffeine from tea leaves and study its absorption properties. 9. Phytochemical screening and qualitative chemical examination of various plant constituents by Solvent extraction. (Detection of alkaloids, carbohydrates, glycosides, phytosterols, oils and fats, tannins, proteins, gums and mucilages). 10. Extraction of piperine from black pepper.

SUGGESTED READINGS 1. Introduction to Medicinal Chemistry, 4th edition (2009), Graham l. Patrick, Oxford University Press. ISBN-13: 978-0199234479. 2. The Organic Chemistry of Drug Design and Drug Action,2nd edition (2004), Richard B. Silvermann, Elsevier, Academic Press. ISBN: 978-0126437324. 3. Medicinal Chemistry: A Molecular and Biochemical Approach, 3rd edition (2005), Thomas Nogrady and Donal F. Weaver, Oxford University Press. ISBN-13: 978- 0195104561. 4. Wilson Gisvold textbook of Organic Medicinal and Pharmaceutical Chemistry, 11th edition (2003), edited by Block and Beale, Baltimore, Lippincot. ISBN-13: 978- 0781734813. 5. The Practice of Medicinal Chemistry, 2nd edition (2003), Camille G. Wermuth, Academic Press. ISBN-13: 978-0127444819. 6. Principles and Practice of Medicinal Chemistry, 2nd edition (2003), Frank. D. King. The Royal Society of Chemistry.ISBN-13: 978-0854046317. 7. Introduction to Medicinal Chemistry: How Drugs Act and Why, 1st edition (1996), Alex Gringauz, Wiley VCH. ISBN-13: 978-0471185451.

B.Sc. (Hons) Course in Biomedical Science III Year Semester V and VI Semester V BMS-501: Biophysics

Preamble: Biological phenomena cannot be understood fully without physical insight. Biophysics is an interdisciplinary frontier of science in which the principles and techniques of physics are applied to understand biological problems at every level, from atoms and molecules to cells, organisms and environment. The work always aims to find out how biological systems work. This paper covers various spectroscopic techniques, hydrodynamic methods, molecular biophysics and introduction to various physical principles responsible for maintaining the basic cellular function and integrity of biological membranes including transport across them.

THEORY Total Lectures: 48

Unit I: Biophysical techniques (20 Lectures)

Basic principles of electromagnetic radiation: Energy, wavelength, wave numbers and frequency, Review of electronic structure of molecules.

UV-visible spectrophotometry: Beer Lambert law, Light absorption and its transmittance, Factors affecting absorption properties of a chromophore, Structural analyses of DNA/ protein using absorption of UV light.

Fluorescence spectroscopy: Theory of fluorescence, Static and dynamic quenching, Resonance energy transfer, Fluorescent probes in the study of protein and nucleic acids.

Optical rotatory dispersion and Circular dichroism: Principle of ORD and CD, Analysis of secondary structure of proteins (denatured and native form) and nucleic acids using CD.

Infra-red spectroscopy: Theory of IR, Identification of exchangeable hydrogen, Number of hydrogen bonds, Tautomeric forms.

Magnetic resonance spectroscopy: Basic theory of NMR, Chemical shift, Medical applications of NMR.

Mass spectrometry (MALDI-TOF): Physical basis and uses of MS in the analysis of proteins/ nucleic acids.

X-ray crystallography: Diffraction, Bragg‟s law and electron density maps (concept of R- factor and B-factor), Growing of crystals (Hanging drop method).

Unit II: Hydrodynamic methods (10 Lectures)

Viscosity: Methods of measurement of viscosity, Specific and intrinsic viscosity, Relationship between viscosity and molecular weight, Measurement of viscoelasticity of DNA.

Sedimentation: Physical basis of centrifugation, Svedberg equation, Differential and density gradient centrifugation, Preparative and analytical ultracentrifugation techniques, Fractionation of cellular components using centrifugation with examples. Flow Cytometry: Basic principle of flow cytometry and cell sorting, Detection strategies in flow cytometry.

Unit III: Molecular biophysics (12 Lectures)

Basic thermodynamics: Concept of entropy, enthalpy, free energy change, heat capacity. Forces involved in biomolecular interactions with examples: Configuration versus conformation, Van der Waals interactions, Electrostatic interactions, Stacking interactions, Hydrogen bond and hydrophobic effect, Ramachandran plot.

Supercoiling of DNA: Linking number, twist and writhe.

Protein folding: Marginal stability of proteins, Thermodynamic and kinetic basis of protein folding, Protein folding problem (Levinthal‟s paradox) and role of molecular chaperones in cellular protein folding, Basics of molecular and chemical chaperones, Protein misfolding and aggregation, Diseases associated with protein misfolding.

Unit IV: Biological membranes (06 Lectures)

Transport of solutes and ions, Fick‟s laws of diffusion, Ionophores, Transport equation, Membrane potential.

PRACTICALS (Any 6) (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Effect of different solvents on UV absorption spectra of proteins. 2. Study of structural changes of proteins at different pH using UV spectrophotometry. 3. Study of structural changes of proteins at different temperature using UV – spectrophotometry. 4. Determination of melting temperature of DNA. 5. Study the effect of temperature on the viscosity of a macromolecule (Protein/DNA). 6. Use of viscometry in the study of ligand binding to DNA/protein. 7. Crystallization of enzyme lysozyme using hanging drop method. 8. Analysis, identification and comparison of various spectra (UV, NMR, MS, IR) of simple organic compounds.

SUGGESTED READINGS

1. Physical Biochemistry: Principles and Applications, 2nd edition (2009), David Sheehan John Wiley. ISBN-13: 978-0470856031. 2. Physical Biochemistry: Applications to Biochemistry and Molecular Biology, 2nd edition (1982), David Freifelder, W.H. Freeman and Company. ISBN-13: 978- 0716714446. 3. Physical Chemistry: Principles and Applications in Biological Sciences, 4th edition (2001), I. Tinoco, K. Sauer, J.C. Wang and J.D. Puglisi, Prentice Hall, ISBN-13: 978- 0130959430. 4. Molecular Biology of the Gene, 7th edition (2007), Watson, J. D., Baker T.A., Bell, S. P., Gann, A., Levine, M., and Losick, R, Benjamin Cummings Publishers, ISBN-13: 978- 0805395921. 5. Biophysics, 1st edition (1983), W. Hoppe, W. Lohmann, H. Markl and H. Ziegler, Springer- Verlag, ISBN-13: 978-3540120834. 6. The Physics of Proteins: An introduction to Biological Physics and Molecular Biophysics, 1st edition (2010), H. Frauenfelder, S.S. Chan and W.S. Chan, Springer, ISBN-13: 978- 1441910431. 7. Principles of Instrumental Analysis, 6th edition (2006), D.A. Skooget. al., Saunders College Publishing. ISBN-13: 978-0495012016. 8. Principles of Physical Biochemistry, 2nd edition (2005), K.E. Van Holde, W.C. Jhonson and P. Shing Ho, Prentice Hall Inc. ISBN-13: 978-0130464279. 9. Biophysical Chemistry, 1st edition (1980), C.R. Cantor, P.R. Schimmel, W.H. Freeman and Company. ISBN-13: 9780716711889. 10. Crystallography Made Crystal Clear: Guide for Users of Macromolecular Models, 3rd edition (2010), Gale Rhodes, Academic Press. ISBN: 9780080455549. 11. Introduction to Protein Structure, 2nd edition (1999), C. Branden and J. Tooze, Garland Publishing, ISBN-13: 978-0815323051.

Semester V BMS 502: Pharmacology

Preamble: Pharmacology is the science concerned with the study of drugs and how they can best be used in the treatment of disease in both humans and animals. The course starts with the general considerations and lead to understanding of various drugs acting on different body systems. It is a very important biomedical discipline, with roots both in basic biology and chemistry, and plays a vital role in helping to safeguard our health and welfare.

THEORY Total Lectures: 48

Unit I: Introduction to Pharmacology (04 Lectures)

Nature and source of drugs, Routes of drug administration- their advantages and disadvantages, Receptor and receptor subtypes.

Unit II: Pharmacokinetics (08 Lectures)

Drug absorption, distribution, metabolism, and excretion. Bioavailability, First Pass metabolism, Excretion and kinetics of elimination, Bioavailability, Biological half life of drug and its significance, Drug-drug interactions.

Unit III: Pharmacodynamics (06 Lectures)

Principles and mechanism of drug action, Factors affecting drug action.

Unit IV: Brief introduction to autacoids (04 Lectures)

Drug therapy of inflammation, NSAID and other drugs (aspirin, celecoxib).

Unit V: Mechanism of action of different classes of drugs (12 Lectures)

General Aspects, Classification and mechanism of action of following classes of drugs along with side effects and contraindication of the drugs mentioned against each class should also be covered. (a) General Anesthetics: Halothane (b) Sedatives and Hypnotics: Diazepam (c) Cholinergics: Bethanechol, Rivastigmine (d) Skeletal Muscle Relaxants: Succinylcholine (e) Adrenergics: Isoprenaline, Propranolol, Salbutamol (f) Dopaminergics: Dopamine, Syndopa (g) Diuretics: Furosemide

Unit VI: Chemotherapy of microbial diseases (06 Lectures)

Antibacterial (sulfonamides), antifungal (amphotericin B).

Unit VII: Horomones and hormone antagonists (08 Lectures)

Insulin and oral hypoglycaemic agent (tolbutamide, rosiglitazone), thyroid and anti-thyroid drugs (eltroxin, carbimazole), HRT, estrogen and progestins (progesterone, hydroxyprogesteronecaproate).

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Handling of laboratory animals. 2. Routes of drug administration (Oral, I.M.) 3. To study the presence of acetaminophen in given sample. 4. To study the stages of general anesthesia. 5. To determine partition coefficient of general anesthetics. 6. Effect of analgesic (Tail-flick test). 7. Anti-anxiety effect of valium (Plus maze test). 8. Fixing of organ bath and kymograph. 9. To record CRC of acetylcholine using guinea pig ileum / rat intestine. 10. Determination of dose ratio. 11. Study of competitive antagonism using acetylcholine and atropine.

SUGGESTED READINGS 1. Essentials of Medical Pharmacology, 7th edition (2010), K.D. Tripathi, Jaypee Brothers, ISBN:9788184480856. 2. Pharmacology, 7th edition (2011), H.P. Rang, M.M. Dale, J.M. Ritter and P.K. Moore, Churchill Livingstone. ISBN:9780702045042. 3. Hand book of Experimental Pharmacology, 4th edition (2012), S.K. Kulkarni, VallabhPrakashan, 2012. ISBN 13: 97881857311 Semester VI BMS 601: Human Pathology

Preamble: The curriculum of Human pathology aims at preparing the students in basic understanding of diseases and their pathogenesis. The topics are of introductory nature and build the concepts of how human system work in altered and diseased stage under the influence of various internal and external stimuli Thus the syllabi of pathology compliments and supplements the necessary knowledge students have gained in Physiology, cell and tissue biology. Consequently it incorporates topics like cellular adaptations, inflammation, neoplasia, cellular ageing and other infectious and non-infectious diseases. Laboratory exercises have been designed to substantiate and clarify the theoretical concepts.

THEORY Total Lectures: 48

Unit I: Introduction (2 Lectures)

History of pathology, Basic definitions and familiarization with the common terms used in pathology, Techniques used in pathology. Basic Concepts in cell and Tissue remodelling.

Unit II: Cellular adaptations, Cell Injury and Cell Death (6 Lectures)

Causes and mechanisms of cell injury: reversible and irreversible injury, Cellular responses: Hyperplasia, Hypertrophy, Atrophy, Metaplasia, Necrosis, Apoptosis, Subcellular and intracellular response, (with suitable examples of diseases), Concepts and mechanisms of cell ageing.

Unit III: Inflammation and its role in diseases (8 Lectures)

General features of acute and chronic inflammation: vascular changes, cellular events, termination of acute inflammatory response, molecular mediators of inflammation, morphological effects and outcome of acute inflammation. Systemic effects of chronic inflammation, Granulomatous inflammation.

Unit IV: Tissue renewal and repair, Healing and Fibrosis (8 Lectures)

Mechanism of tissue regeneration, Role of ECM, Repair by healing, Scar formation and fibrosis, Cutaneous wound healing, Fractures and healing. Tissue remodelling in liver (mechanism of fibrosis and cirrhosis), Rheumatoid arthritis.

Unit V: Hemodynamic Pathology (6 Lectures)

Edema, Hyperemia, Congestion, Haemorrhage, Haemostasis and thrombosis, Embolism, Infarction, Shock, Hypertension.

Unit VI: Tumor pathology and Pathogenesis (8 Lectures)

Definitions, Nomenclature, Characteristics of benign and malignant neoplasms, Grading and staging of cancer, Biology of tumor growth, Mechanism of tumor invasion and metastasis, Carcinogens and cancer, Concept of oncogenes, Tumor suppressor genes, DNA repair genes, Cancer stem cells.

Unit VII: Pathophysiology of diseases (10 Lectures)

A. Etiology and pathophysiology of Lifestyle diseases: Diabetes, Atherosclerosis, Myocardial infarction, Asthma B. Etiology and Pathophysiology of Infectious diseases: Diarrheal diseases like Cholera, Tuberculosis

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Urine Analysis: Gross examination of urine for colour, odour etc. Abnormal constituents like protein, ketone bodies, glucose, blood, urea (any three). 2. Tissue Processing, embedding and sectioning. Staining and preparation of permanent histological slide. 3. Study of histological slides showing hypertrophy, hyperplasia, dysplasia, leukemia, cirrhosis and any common cancer. 4. Diagnostic tests for detection of various Diseases – CRP, VDRL, RA, Pregnancy, Dengue and HIV (any four). 5. Physiological data acquisition like Temperature EEG. 6. PCR based diagnostics (for any one disease). 7. Measurement of Erythrocyte Sedimentation Rate. 8. Study of fractures through X rays films.

SUGGESTED READINGS

1. Robbins and Cotran Pathologic Basis of Disease, 8th edition (2009), Vinay Kumar, Abul K. Abbas, Jon C. Aster, Nelson Fausto; Saunders Publishers, ISBN-13: 978-1416031215. 2. General and Systematic Pathology, 2nd edition (1996), J., Ed. Underwood and J. C. E. Underwood; Churchill Livingstone, ISBN-13: 978-0443052828. 3. Robbins Basic Pathology, 9th edition (2012), Kumar, Abbas, Fausto and Mitchell; Saunders Publication, ISBN-13: 978-1437717815. 4. Medical Laboratory Technology Methods and Interpretations Volume 1 and 2, 6th edition (2009), Ramnik Sood; Jaypee Brothers Medical Publishers, ISBN-13: 978-8184484496. 5. Pathophysiology, 3rd edition (2012), Lee-Ellen C. Copstead-Kirkhorn and Publisher Saunders, ISBN-13: 978-1455726509.

Semester VI BMS 602: Toxicology

Preamble: Different types of poisons have been known to humans since ages. Even in early times when science was in its infancy, curious people such as “Paracelsus” could predict “Every substance is a poison and, it is the right dose of the substance which differentiates remedy from poisons”. This thought is fundamental even to modern toxicology and pharmacology. There is an increasing use of chemicals in the modern society and hence, toxicology is becoming a more important subject to study with the passage of time. Modern toxicology is a vast, multidisciplinary subject encompassing various other basic fields of science. The present course content is designed to provide the basics of toxicology. Relevant importance has been given to those topics which can build a strong foundation in the subject, based on which, facts can be assimilated during subsequent higher studies.

THEORY Total Lectures 48

Unit I: Introduction (2 Lectures)

Brief history, Different areas of modern toxicology, Classification of toxic substances, Various definitions of toxicological significance.

Unit II: Toxic exposure and response (5 Lectures)

Effect of duration, frequency, route and site of exposure of xenobiotics on its toxicity. Characteristic and types of toxic response. Types of interactions between two and more xenobiotics exposure in humans. Tolerance and addiction.

Unit III: Evaluation of toxicity (2 Lectures)

Various types of dose response relationships, assumptions in deriving dose response, LD50, LC50, TD50 and therapeutic index.

Unit IV: Mechanism of toxicity (10 Lectures)

Delivery of the toxicant, Mechanisms involved in formation of ultimate toxicant, Detoxification of ultimate toxicant.

Unit V: Fate of xenobiotics in human body (10 Lectures)

Absorption, distribution, excretion and metabolism of xenobiotics (biotransformation, Phase- I reactions including oxidations, hydrolysis, reductions and phase II conjugation reactions).Toxic insult to liver, its susceptibility to toxicants with reference to any two hepatotoxicants.

Unit VI: Toxic agents (8 Lectures)

Human exposure, mechanism of action and resultant toxicities of the following xenobiotics: Metals: lead, arsenic, Pesticides: organophosphates, carbamates, organochlorine, bipyridyl compounds and anticoagulant pesticides.

Unit VII: Eco-toxicology (7 Lectures)

Brief introduction to avian and aquatic toxicology, Movement and effect of toxic compounds in food chain (DDT, mercury), Bioaccumulation, Biomagnification, Acid rain and its effect on ecosystems, Concept of BOD and COD.

Unit VIII: Clinical toxicology (4 Lectures)

Management of poisoned patients, Clinical methods to decrease absorption and enhance excretion of toxicants from the body, use of antidotes.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Separation of a mixture of benzoic acid, beta- naphthol and naphthelene by solvent extraction and identification of their functional Groups. 2. Determination of Dissolved oxygen (DO) using Winkler‟s method. 3. Determination of Biological oxygen demand (BOD) of water. 4. To perform quantitative estimation of residual chlorine in water samples. 5. To determine the total hardness of water by complexo-metric method using EDTA. 6. To determine acid value of the given oil sample. 7. To estimate formaldehyde content of given sample. 8. Calculation of LD50 value of an insecticide from the data provided. 9. Determination of COD (chemical oxygen demand) of the given water sample.

SUGGESTED READINGS 1. Cassarett and Doull‟s Toxicology “The Basic Science of The Poisons” 7th edition (2008), Curtis D. Klaassen Editor, McGrawHill Medical. ISBN: 9780071470513. 2. Cassarett and Doull‟s “Essentials of Toxicology” 2nd edition (2010), Klaassen and Whatkins, McGraw Hill Publisher. ISBN-13: 978-0071622400. 3. Introduction to Toxicology, 3rd edition (2001), John Timbrell, Taylor and Francis Publishers. ISBN 13: 9780415247627. 4. Principles of Toxicology, 2nd edition (2006), Stine Karen and Thomas M Brown, CRC press. ISBN-13: 978-0849328565. 5. Lu‟s basic toxicology: Fundamentals target organ and risk assessment, 5th edition (2009), Frank C Lu and Sam Kacow, Informa Health care. ISBN: 9781420093117.

Skill Enhancement Courses (SEC)

B.Sc. (Hons) Course in Biomedical Science

Semester III and IV BMS-S1: Methods for Epidemiological Data Analysis

Preamble: In public health work, one may be concerned with planning of experiments and the analysis of their results. Therefore, one has to deal with statistical data analyses that come from no deliberate experiment but that arise because of the data collected from the population in the course of public health study and survey. This course therefore provides training to the students on how to conduct epidemiological surveys, design questionnaire and analyze the data. The students will get hands-on-training on „R‟, a free software environment for statistical computing and graphics.

Total sessions: 12 (Each session of 2 Lectures and 4 practical classes)

Unit I: Understanding epidemiological data (1 session)

1. Analysis of data from National Cancer Registry Program (NCRP) 2. Understanding incidence, mortality (rates, ratios and proportions) Components of epidemiology: disease frequency, distribution of disease and determinants of disease. Epidemiological approach and measurements- vital statistics (rates, ratios and proportions), Measurements of health indicators (morbidity, mortality and fertility rates).

Unit II: Epidemiologic methods and survey# (4 sessions)

1. Designing a questionnaire for survey of prevalence diabetes/ hypertension/ allergy/ respiratory disorders/etc. 2. Defining the parameters for ethical issues in a study 3. Determining the target and control populations 4. Surveying the population for the diseases mentioned above Data collection: observational (descriptive and analytical) and experimental studies. Epidemiology study designs- case control and cohort studies (prospective and retrospective), Techniques of sampling and matching, Sources of bias.

#Conducting survey is optional and data can be extracted from public domains like WHO for analysis

Unit III: Data organization and presentation (2 sessions)

Introduction to ‘R’ software 1. Analysis of data from NCRP data and survey conducted by the students Basic principles of „R‟ software for tabulation and graphical representations (bar diagrams, histograms, pie charts, box plot, etc.), Measures of central tendency (mean, mode, median and partition values), Dispersion (range, standard deviation, coefficient of variance and covariance) and Skewness.

Unit IV: Statistical modeling and analysis using ‘R’ on NCRP data and survey conducted by the students (5 sessions)

1. Correlation studies 2. Regression studies 3. Probabilistic distribution studies 4. Comparison of groups and ascertaining statistical significance of differences

Correlation analysis (scatter diagrams and Karl Pearsons coefficient of determination, standard and probable errors) and regression analysis. Inferential statistics: sampling distributions and standard error, null and alternate hypothesis, basic concept and illustrations of type I and type II errors, concept of confidence interval estimation, large sample tests for single mean and difference of means, single proportion and difference of proportions, students t-distribution (test for single mean, difference of means and paired t-test), chi-square distribution, F-distribution, one-way and two-way ANOVA, non parametric analysis (sign and rank tests), p-value.

SUGGESTED READINGS 1. Park‟s Textbook of Preventive and Social Medicine, 21st edition (2011), K. Park, M/s Banarsi Das Bhanot Publishers. ISBN13: 9788190607995 2. Primer of Biostatistics, 7th edition (2011), Stanton Glantz, McGraw-Hill Medical. ISBN-13: 978-0071781503. 3. Basic epidemiology, 2nd edition (2006), R. Bonita, R. Beaglehole, TordKjellstrèom, Contributor; World Health Organization, illustrated, Publisher: World Health Organization, ISBN-13: 978-9241547079. 4. Biostatistics: A Foundation for Analysis in the Health Sciences, 10th edition (2013), Wayne W Daniel and Chad L. Cross, Wiley. ISBN-13: 978-1118302798. 5. Principles of Biostatistics, 2nd edition (2000), Marcello Pagano and KimberleeGauvrean, Thompson learning. ISBN-13: 978-0534229023. 6. Biostatistical Analysis, 5th edition (2009), Jerrold H. Zar, Pearson. ISBN-13: 978- 0131008465. Website for ‘R’: www.r-project.org Website for NCRP: http://www.ncrpindia.org/

BMS-S2: Medical Laboratory Diagnostics (MLD)

Preamble: Medical Lab Diagnostics would help students enhance their practical skills and would enable them work in a Hospital setup. The paper is divided into three modules. First of all the students would orient themselves to work in a proper diagnostic setting. Secondly students would be introduced to detection of diseases using microbiological and molecular methods. Finally they would enhance their skills by learning various cytogenetic disorders. By this time students would have been also exposed to various techniques used in Biochemistry. Therefore, after the exposure of the current paper they would find themselves equipped with a full package of skill development in order to work in a diagnostic setting.

Total sessions: 12 (Each session of 2 Lectures and 4 practical classes)

Unit I: Fundamentals of Clinical Diagnostics (4 sessions)

Laboratory 1: Principles and applications of important instruments used in the diagnostic laboratory: biological safety cabinets (Class I, II, III) autoclave, incubators, hot air oven, centrifuges, PCR machines, bright field microscope, fluorescence microscope, ELISA reader, Spectrophotometer, Gel Electrophoresis System.

Laboratory 2: Field visit to any diagnostic setting to explain the concepts of automation and total quality management used in clinical labs.

Laboratory 3 and 4: Antigen-antibody interaction and its use in applications for the detection and diagnosis of common diseases: Widal test for typhoid, Acetylated haemoglobin in Diabetes, TSH levels in Thyroid condition, Malaria antigen in Malaria, NS1 antigen in Dengue (any two immune diagnostic tests).

Introduction to clinical laboratory principles and procedures. Guidelines for collection, transport, preservation, processing and analysis of specimen. Overview of phlebotomy, urinalysis, basic hematology, clinical biochemistry, immune-serology and clinical microbiology. Guidelines for proper discard of biological waste and chemical wastes.

Concepts of Immune response to be explained. Techniques to be discussed: ELISA - direct, indirect, competitive and sandwich ELISA, Different approaches used in molecular diagnostics.

Different approaches used in molecular diagnostics examples PCR and qPCR.

Unit II: Diagnosis of infectious diseases (4 sessions)

Laboratory 5: To study composition and use of important media for identification of bacteria PCA agar, EMB agar, McConkey agar, TCBS agar and Salmonella-Shigella agar and blood culture media (any two).

Laboratory 6: Isolate and enumerate the microbial load present on fresh produce. Further use selective media to differentiate the various bacteria for microbial identification.

Laboratory 7: Study of morphological and biochemical characteristics of the isolated bacteria.

Laboratory 8: PCR based detection and verification of the isolated bacteria. Classification of culture media and quality control of culture media. Innoculation, incubation and purification methods in bacteriology. Preservation of bacterial culture. Rapid identification system, Continuous monitoring culture systems: BacT/ESP/BACTEC.

Use of conventional microbiological tools supplemented by most modern analytical techniques including PCR for enumeration, isolation and identification of microbes (mainly on fresh produce).

Setting up “Gold Standard” method. Concepts of accuracy (efficiency), precision, sensitivity, specificity, prevalence positive predictive value and negative predictive value.

Unit III: Medical Cytogenetics (4 sessions)

Laboratory 9: Preparation of metaphase chromosomes.

Laboratory 10: Understanding chromosome banding and karyotyping techniques, normal and diseased.

Human cytogenetics and its application to medicine, Cell culture and harvest, Chromosome banding and staining, Chromosome identification, Cytogenetics nomenclature, Chromosome abnormalities and aberrations, Chromosomal syndromes, Classification of genetic disorders, Disciplines within Clinical Genetics and integration of genetic diagnostic services with other healthcare services (Clinical Genetics, Prenatal Diagnosis, Infertility, Cancer Cytogenetics).

Students’ Presentations (2 sessions)

Understand issues related to the interpretation of normal chromosomal variation (with the help of photographs), Examples like mosaicism, aneuploidy and other chromosomal rearrangements, ISCN nomenclature, Abnormalities of chromosome number (monosomy, trisomy, triploidy), Partial aneuploidy, microdeletion/contiguous gene syndromes, abnormal chromosomes.

Skills that are developed at the end of this course: 1. The student will demonstrate knowledge of how to obtain reliable information from a variety of sources (e.g. web, popular media, and scientific publications). 2. Practical training to work in diagnostic setting increased. 3. The student will demonstrate knowledge of how to communicate the results of a scientific investigation.

SUGGESTED READINGS 1. Bailey and Scott‟s Diagnostic Microbiology, 12th edition (2007), Betty A. Forbes, Daniel F. Sahm and Alice S. Weissfeld; Mosby Elsevier Publishers, ISBN-13: 978-0808923640. 2. Medical Laboratory Technology Methods and Interpretations Volume 1 and 2, 6th edition (2009), Ramnik Sood; Jaypee Brothers Medical Publishers, ISBN-13: 978-8184484496. 3. Current Protocols in Human Genetics, 1st edition (1994), Dracopoli and Nicolas C. Dracopoli; John Wiley and Sons, Inc., ISBN-13: 978-0471034209. 4. Molecular Cloning: A Laboratory Manual, 4th edition (2012), Michael R. Green and Joseph Sambrook; Cold Spring Harbor Laboratory Press, ISBN-13: 978-1936113422. 5. Microbiology: A Laboratory Manual, 10th edition (2013), James Cappuccino and Natalie Sherman, Benjamin Cummings, ISBN-13: 978-0321840226. BMS-S3: Techniques for Forensic Science

Preamble: Forensic science is the application of scientific knowledge to questions of civil and criminal law. Interest in forensic science has grown considerably in recent years. Kee ping this in view, the present forensic science course is designed for students to explore how forensic scientist‟s work, the tools and techniques they use and how they reach the conclusions they present in court. This engage students in using a creative, problem solving and inquiry based approach to investigate the crime scene. It also explains the characteristics of a fingerprint collect, process, and analyze fingerprint evidence and explain DNA analysis.

Total sessions: 12 (Each session of 2 Lectures and 4 practical classes)

Unit I: Crime scene investigation (2 Sessions)

Laboratory 1: Documentation of crime scene by photography, sketching and field notes. Laboratory 2a: Simulation of a crime scene for training. Laboratory 2b: To lift footprints from crime scene.

Introduction and principles of forensic science, Forensic science laboratory and its organization and service, tools and techniques in forensic science, branches of forensic science, causes of crime, role of modus operandi in criminal investigation.

Unit II: Examination of security documents (1 session)

Laboratory 3: Examination of documents (Indian Passports/Visas, Stamp Papers, Postal Stamps etc.) with important security features, Physical matching of documents.

Introduction to various security features in documents, methods of security document examinations.

Unit III: Forensic chemistry and ballistics (2 sessions)

Laboratory 4a: Comparison of bullets and cartridges in museum. Laboratory 4b: Separation of nitro compounds (explosives) by thin layer chromatography. Laboratory 5: To perform the preliminary examination of blood in a given sample.

Classification of fire arms and explosives, introduction to internal, external and terminal ballistics, Chemical evidence for explosives.

Unit IV: Forensic graphology (2 sessions)

Laboratory 6: Identification and comparison of handwriting characters. Laboratory 7: To perform thin layer chromatography of ink samples.

General and individual characteristics of handwriting, examination and comparison of handwritings and analysis of ink various samples.

Unit V: Forensic toxicology (1 session)

Laboratory 8: Identification techniques of common toxins, drugs, pesticides, Volatile poisons, vegetable poisons etc. in given biological samples and crime scene. Role of the toxicologist, significance of toxicological findings.

Unit VI: Fingerprint analysis (1 session)

Laboratory 9a: Investigate method for developing fingerprints by Iodine crystals. Laboratory 9b: To observe the effects of surface temperature on fingerprints.

Fundamental principles of fingerprinting, classification of fingerprints, development of finger print as science for personal identification.

Unit VII: DNA Finger printing (2 sessions)

Laboratory 10: DNA isolation in minimal available biological samples. Laboratory 11: PCR amplification of target DNA and DNA profiling.

Principle of DNA fingerprinting, Application of DNA profiling in forensic medicine.

Unit VIII: Cyber forensic investigation (1 session)

Laboratory 12a: Digital Evidence Collection. Laboratory 12b:E-Mail Investigation, E-Mail Tracking, IP Tracking, E-Mail Recovery, Recovering deleted evidences, Password Cracking. Investigation Tools, eDiscovery, Evidence preservation, Search and seizure of computers, Introduction to cyber security.

SUGGESTED READINGS 1. Forensic Science – An introduction to Scientific and Investigative Techniques, 3rd edition (2009), James SH, Nordby JJ and Bell S; CRC Press, ISBN-13: 978-1420064933. 2. Practical Forensic Microscopy: A laboratory manual, 1st edition (2008), Barbara Wheeler and Lori J Wilson; Bios Scientific Publisher, ISBN-13: 978-0470031766. 3. Forensic Handwriting Identification: Fundamentals, Concepts and Principals 1st edition (2000) Ronald N. Morris, Academic press ISBN-13: 978-0125076401 4. Handbook of Firearms and Ballistics: Examining Interpreting Forensic Science by Brian J Heard 2nd edition (2008), John Wiley and Sons ISBN-13: 978-0470694602. 5. Principles of Forensic Medicine and Toxicology, 1st edition (2011) Rajesh Bardale; Jaypee Brothers Medical Pub, ISBN-13: 978-9350254936. 6. Practical Crime Scene Processing and Investigation, 2nd edition (2011), Ross M Gardner, CRC press ISBN-13: 978-1439853023. 7. Forensic Medicine and Toxicology: Oral, Practical And Mcq, 3rd edition (2006), Karmakar,Jaypee Brothers, ISBN-13:978-8171797350. 8. Fundamentals of Forensic Science, 2nd edition (2010), Houck, M.M. and Siegel, JA; Academic Press, ISBN-13: 978-0123749895. 9. Criminalistics- An Introduction of Forensic Science, 10th edition (2010), Prentice Hall Inc; ISBN-13: 978-0135045206.

BMS-S4: Tools in Modern Biology

Preamble: This course has been designed to introduce the various tools and techniques in modern era of biology and biotechnology. The philosophy behind this course is to make the students appreciate various processes and techniques they learn in other courses with hands-on training and experience. The emphasis is laid on techniques and tools in understanding DNA and proteins- the building blocks of life. It focuses on the principles of amplification, purification and analysis of DNA sequences by the means of plasmids, PCR and mapping. It also accounts for purification and study of protein-protein interactions besides giving an overview of cell culture.

Total sessions: 12 (Each session of 2 Lectures and 4 practical classes)

Unit I: Plasmids and Biotechnology (3 sessions)

1. Isolation of Plasmid (mini-prep) from E. coli culture 2. Restriction digestion of plasmid and its analysis 3. Extraction of DNA from agarose gel 4. Construction of restriction maps from the data provided

Significance of plasmids in biotechnology. Different methods of plasmid isolation. Types and relevance of restriction sites and their potential in mapping.

Unit II: Amplification and analysis of DNA sequences (3 sessions)

1. Primer designing 2. Optimization of PCR conditions for temperature (gradient PCR) and Mg2+ concentration 3. Detection of bacteria specific genes using colony PCR 4. Analysis of DNA sequences with electropherograms

Principle, applications and modifications of PCR, Essentials for a primer, Concept of DNA sequencing and analysis of electropherograms.

Unit III: Purification and analysis of Proteins (4 sessions)

1. Comparative analysis of protein on native and denaturing gels 2. Protein purification by affinity chromatography 3. Separation of proteins by ion exchange chromatography

Concept of protein structure and denaturation with relevance to its resolution on gel, principle of chromatography and its application in purification and studying interactions.

Unit IV: Cell culture and Imaging (2 sessions)

1. Preparation of media and culturing of cells 2. Fluorescence imaging demonstration in E. coli with GFP and mammalian cells with PI/DAPI

Essentials of cell culture, Composition of media and the variations therein, Analysis of the status within using fluorescence microscopy. SUGGESTED READINGS 1. Gene cloning and DNA analysis, 6th edition (2010), T.A. Brown. Wiley-Blackwell ISBN-13: 978-1405181730. 2. Human Molecular Genetics, 3rd edition (2003), Tom Strachan and Andrew Read; Garland Science Publishers, ISBN -13:978-0815341826. 3. Physical Biochemistry: Applications to Biochemistry and Molecular Biology, 2nd edition (1982), David Freifelder, W.H. Freeman and Company. ISBN-13: 978-0716714446. 4. Principles and Techniques of Biochemistry and Molecular Biology 7th edition (2010), Wilson K and Walker J. Cambridge University Press, 2010. ISBN-13: 9780521516358. 5. Principles of Gene Manipulation and Genomics, 7th edition (2006), S.B. Primrose and R.M. Twyman. Blackwell Scientific ISBN-13: 978-1405135443. 6. Molecular Biotechnology: Principles and Applications of Recombinant DNA, 4th edition (2009), Bernard R. Glick, Jack J. Paternack, Cheryl I. Patten. ASM press, ISBN- 13:9781555814984. 7. Molecular Cloning: A Laboratory Manual, 4th edition (2012), Three-volume set by Michael R. Green, Joseph Sambrook; Cold Spring Harbor Laboratory Press, ISBN-13: 978-1936113422. 8. Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th edition (2010), ISBN-13: 978-0470528129.

Discipline Specific Elective (DSE) Courses

B.Sc. (Hons) Course in Biomedical Science

Semester V and VI

(Any two papers per semester in semesters 5-6)

BMS-A: Biosafety and Bioethics BMS-B: Computational Biology and Drug Design BMS-C: Genome Organization and Function BMS-D: Human Genetics BMS-E: Medical Biochemistry BMS-F: Medical Biotechnology BMS-G: Project Work (can be chosen only in semester 6)

BMS A: Biosafety and Bioethics

Preamble: The recent advances in the field of biotechnology have brought into focus several safety and ethical issues. The inventions in the field of genetic engineering and related fields of molecular biology not only affect us but also the plants, microflora, animals and the entire environment and the way we practice agriculture, medicine and food processing. An increase in our ability to change life forms in recent years has given rise to the new science of bioethics. The present course focus is on the biosafety and bioethical issues the modern society confronts. Topics such as biosafety levels, GM food debate, impact of biotechnology on biosafety, biotech products and ethical issues, governance of biosafety, environmentally responsible use of biotechnology, clinical ethics will be discussed in the curriculum.

THEORY Total Lectures: 48

Unit I: Foundation of bioethics and Introduction to biosafety. (06 Lectures)

Definition of Bioethics: historic evolution, codes and guidelines, universal principles. CPCSEA guidelines for animal handling and ethical use of animal in the laboratory and Outline of WHO guidelines. Historical background of biosafety. Introduction to biological safety cabinets ( Level, I, II III, and international bylaws) Primary containment for biohazards. Biosafety levels of specific microorganisms, recommended handling and biosafety levels for infectious agents (including microorganism) and infected animals, Animal workstations and dissection units.

Unit II: Biosafety guidelines and management (14 Lectures)

Government of India definition of genetically modified organisms (GMOs) and living modified organisms (LMOs), Roles of institutional biosafety committee, Review committee on genetic manipulation (RCGM), genetic engineering approval committee (GEAC) for GMO applications in food and agriculture, Environmental release of GMOs. The GM-food debate and biosafety assessment procedures for biotech foods and related products, including transgenic food crops, Case studies of relevance. Biosafety assessment of pharmaceutical products such as drugs/vaccines etc. Key to the environmentally responsible use of biotechnological products and techniques, Social and ethical implications of biological weapons (Bioterrorism).

Unit III: Handling and transportation of GM, infectious and radioactive materials (05 Lectures)

Risk analysis, risk assessment, risk management and communication, Overview of national regulations and relevant international agreements including Cartagena Protocol. Handling, transportation and biosafety levels of radioactive material (chemical, biochemical, tissues).

Unit IV: Concept of social aspects in health science (02 Lectures)

Social issues in assessment of health science, its principles to study, cause of health problems and suggest appropriate intervention.

Unit V: Good Medical Practices: Codes, Covenants, Declarations and Guidelines (05 Lectures) Define the term “Bioethics” in relation to profession, society, and biomedicine, which have relevance to bioethics. Guidelines of GMC according to European Medical Practices and CDSCO(central drug standard control organization) on good medical practice.

Unit VI: Clinical ethics (02 Lectures)

Describe the sanctity of human life and the need to preserve human life, Explain about issues related to prenatal screening, clinical trials (Phase I/II/III/IV) studies.

Unit VII: Men and Women health ethics (04 Lectures)

Examination and screening of human population (men and women of all ages) for disease, Addressing the social issues like domestic violence and female genital mutilation and abortion Vulnerability of women with respect to health care, Introduction of men and women legal rights for medical examination and treatment.

Unit VIII: Medical errors and negligence (03 Lectures)

Medical error and medical negligence according to Indian Penal code, A clear distinction between Medical error and medical negligence, Remedies against Medical error and medical negligence, Protection and compensation related to it.

Unit IX: Critical care ethics (04 Lectures)

History and need for ICU care, Functioning and ethical principles of ICU care, triage and futility, end of life care. Eethical principles related to withholding treatment and withdrawing treatment (euthanasia), legal position regarding policies in ICU and handling of conflicts in the ICU.

Unit X: Care in HIV and AIDS (03 Lectures)

Basics of HIV infection and its prevention, Provision of Medical facilities and identification of ethical issues in clinical practice of HIV medicine, Research ethics related to HIV experiments in vitro, in vivo and human subjects.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. A case study based on genetic modified organism (Bt-Cotton). 2. A case study based on genetic modified organism (Bt-Brinjal). 3. A case study based on terminator seeds. 4. A case study based on clinical trials of vaccines with emphasis on ethical issues. 5. A case study on clinical trials of drugs in India with emphasis on ethical issues. 6. A case study on women health ethics. 7. A case study on medical errors and negligence. 8. A case study on ethical issues in clinical practice of AIDS. 9. A case study on handling and disposal of radioactive waste.

SUGGESTED READINGS 1. Bioethics and Biosafety, 1st edition (2008), M. K Sateesh, I K International Pvt Ltd, ISBN13: 978-8190675703. 2. The Cambridge Textbook of Bioethics, 1st edition (2008), Peter A. Singer and A. M. Viens; Cambridge University Press, ISBN-13: 978-0511545566. 3. Foundation of Bioethics, 2nd edition (1996), E. H Tristram; Oxford University Press, ISBN13: 9780195057362. 4. Social science: An introduction to the study of society, 14th edition (2010), Hunt, E. F.,and Colander, D. C. ; Peason/Allyn and Bacon, Boston, ISBN-13: 978-020570271. 5. Principles of Biomedical Ethics, 6th edition (2011), Beauchamp Tl, Childress JF; Oxford University Press, 2001. ISBN-13: 978-0195143317. 6. A Companion to Bioethics, 2nd edition (2012), Helga Kuhse, Peter Singer; John Wiley and Sons, ISBN-13: 978-1444350845. 7. Bioethics: An Introduction to the History, Methods, and Practice, 1st edition (1997), Nancy Ann SilbergeldJecker, Albert R. Jonsen, Robert A. Pearlman; Jones and Bartlett Learning, ISBN-13: 978-0763702281. 8. Genetically Modified Organisms and biosafety, 1st edition (2004), Tomme Young. ISBN13: 978-2831707983. 9. Environmental Safety of Genetically Engineered Crops, 1st edition (2011), Rebecca Grumet, James F. Hancock, Karim M. Maredia, CholaniWeebadde, Michigan State University Press ISBN-13: 978-1611860085. 10. Biosafety and Bioethics, 1st edition (2006), Rajmohan Joshi; Isha Books ISBN-13: 978- 8182053779. 11. Bioethics and biosafety in biotechnology, 1st edition (2007), V. Sreekrishna; New Age International (P) Ltd., ISBN-13: 978-8122420852.

BMS B: Computational Biology and Drug Design

Preamble: This course will introduce the discipline of computational biology and drug design. It has been designed to explain the different aspects of nucleotide and protein sequence analyses, sequence alignments and their applications in understanding biology. The course will also emphasize on the strategic issues in drug discovery and development, principles of computational methods involved in lead generation virtual screening, quantitative structure- activity relationship and molecular docking.

THEORY Total Lectures: 48

Unit I: Introduction to computational biology (2 Lectures)

What is computational biology and bioinformatics, internet and bioinformatics, chemoinformatics. Introduction to linux and common terminal commands.

Unit II: Biological databases and genome browsers (10 Lectures)

Introduction to various databases and their classification (primary and secondary databases) e.g. NCBI, DDBJ, EMBL, ENSEMBL, UCSC and their use in laboratories: literature, sequence, structure, medical, enzymes and metabolic pathways databases.

Unit III: Sequence alignment and visualization (8 Lectures)

Local and global sequence alignments (Needleman-Wunsch and Smith-Waterman algorithms), pair-wise (BLAST and FASTA algorithms) and multiple sequence alignment (Clustal W) and its importance. Theory behind BLAST- how Hidden Markov Model (HMM) can be used to model a family of unaligned sequences or a common motif within a set of unaligned sequences and further be used for discrimination and multiple alignment, BLAST score, amino acid substitution matrices, s-value and e-value, Calculating the alignment score and significance of e and p value.

Unit IV: Phylogenetic analysis (4 Lectures)

Basics and tools for phylogenetic analysis, cladistics, tree-building methods (character and distance based methods), Construction of phylogenetic trees (PHYLIP) and identifying homologs.

Unit V: Microarray analysis (3 Lectures)

Introduction and use of DNA microarray to assay gene expression. Designing of the experiment, analysis and biological interpretation, Principle and applications of protein microarray.

Unit VI: Drug discovery pipeline (3 Lectures)

Drug life cycle, stages of drug discovery and strategic issues in drug discovery.

Unit VII: Lead generation (6 Lectures)

2D and 3D molecular structures, Molecular descriptors and fingerprints, Molecular similarity and diversity, Topological descriptors, quantitative structure-property relationships.

Unit VIII: Overview of drug development (12 Lectures)

HTS, clinical trials, Applications of chemoinformatics in drug research, Chemical libraries, Protein 3D modeling, characterization of binding site, virtual screening, protein-ligand interactions, Prediction of pharmacological properties, Introduction to drug databases, PubChem and their use in drug development, Lipinski‟s rule of five, concept of energy minimization and force fields, introduction to rational drug design using example.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Retrieval of information from databases. 2. Sequence alignment using BLAST and Clustal W. 3. Phylogenetic analysis using PHYLIP. 4. Microarray analysis using Bioconductor. 5. Molecular format conversion and hands-on molecular visualization program for displaying, animating and analyzing large bio-molecular systems using 3-D graphics. 6. Homology Modeling using SPDBV, model structure refinement using SPDBV and model validation using What Check and Pro Check. 7. Comparing structures, mutations, studying interactions creating electrostatic potential diagrams. 8. Virtual screening and molecular docking.

SUGGESTED READINGS 1. Bioinformatics: Sequence and Genome analysis, 2nd edition (2004), David W. Mount, Cold Spring Harbour Laboratory Press. ISBN-13: 978-0879697129. 2. Bioinformatics: A practical guide to the analysis of genes and proteins, 3rd edition (2004), Andreas D. Baxevanis and B.F. Francis Ouellette, John Wiley and Sons. ISBN-13: 978- 0471478782. 3. Introduction to Medicinal Chemistry, 4th edition (2009), Graham l. Patrick, Oxford University Press. ISBN-13: 978-0199234479. 4. The Process of New Drug Discovery and Development, 2nd edition (2006), C.G. Smith and J.T. O‟Donnell, Informa Healthcare, ISBN-13: 978-0849327797. 5. Cheminformatics (2003), J. Gasteiger, Thomas Engel; Wiley-VCH. ISBN: 9783527618279. 6. Molecular modeling - Principles and Applications, 2nd edition (2003), A. R. Leach, Pearson Education Limited, UK. ISBN 13: 9780582382107. 7. Cheminformatics in Drug Discovery (2006), edited by. T.I. Opera; Wiley Publishers, ISBN: 9783527604203. 8. Molecular dynamics simulation: elementary methods (1992), J. M. Haile, Wiley- Interscience, New York. ISBN-13: 978-0471184393.

BMS C: Genome Organization and Function

Preamble: The paper Genome Organization and Function deals with the more intriguing concepts of gene regulation (transcriptional, translation and genomic), gene silencing, RNAi and forms and mechanisms of regulatory RNAs. The organization of the genome from overlapping genes in bacteria and DNA of cell organelles to the abundance of repetitive DNA in higher organisms will be discussed. The paper concludes with an introduction to the different model organisms, what they are used for and how the student may use these organisms employing modern technological approaches for research and understanding of biology.

THEORY Total Lectures: 48

Unit I: Organization of Human genome (8 Lectures)

General features: Genome size, gene density and diversity, Types of repetitive DNA, gene families and super families, Pseudogenes and processed pseudogenes, RNA encoding genes. Nucleosomes: Basic unit of DNA condensation, Packaging of DNA into chromosome structure, Nucleosome assembly.

Unit II: Gene regulation in Prokaryotes and Eukaryotes (25 Lectures) a) Transcriptional regulation in prokaryotes: Principles of transcriptional regulation. Bacterial gene regulation with reference to lactose, tryptophan and arabinose operon. Role of sigma factors in gene expression. b) Eukaryotic gene regulation: Transcriptional control - Conserved mechanism of regulation, activators, signal integration, combinatorial control, transcriptional repressors, signal transduction and control of transcriptional regulators, examples of steroid receptors, MAP kinase and STATs pathways. c) Eukaryotic gene regulation: Post-transcriptional control, Regulation of translation, Translation-dependent regulation of mRNA and protein stability, post-translational control and role of ubiquitin. d) Eukaryotic gene regulation: Genomic control – gene amplification and deletions, DNA rearrangements, Chromosome puffs, DNA methylation, CpG islands, Changes in histone and chromosome remodeling proteins, Nucleosome modifications, Nucleosomes positioning.

Unit III: Regulatory RNAs (05 Lectures)

Riboswitches, RNA interference, miRNA, siRNA, Piwi-interacting RNA, Regulatory RNA and X-inactivation (reference of calico cats).

Unit IV: Understanding gene function through model organisms (10 Lectures)

Model organisms and the need to study them. Mechanism of choosing the right model organism. Advantages and disadvantages of the organism as a model. Study of model systems in developmental genetics. Early studies of the organism as a Model organism, life cycle, Genetic techniques and Use of the organism as model organism today. Different types of model organisms: Escherichia coli, Saccharomyces cerevisiae (Baker‟s yeast), Drosophila melanogaster (Fruit fly), Mus musculus (Mouse), Danio rerio (Zebra fish)

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Preparation of various stock solutions for mentioned experiments. 2. Comparative analysis of genomic DNA and plasmid DNA by restriction enzyme digestion and estimation of size of a DNA fragment after electrophoresis using DNA markers. 3. Quantification of unknown DNA using Lambda-HindIII marker. 4. Perform Southern Hybridization. 5. Perform Western Blotting. 6. Drosophila as a model system for studying toll-9 gene for Asthma using bioinformatics tools. 7. Isolation and Identification of Auxotrophic and Drug Resistant Mutants of E. coli.

SUGGESTED READINGS

1. Molecular Biology of the Gene, 6th edition (2007), Watson, J. D., Baker T.A., Bell, S. P., Gann, A., Levine, M., and Losick, R; Benjamin Cummings Publishers, ISBN-13: 978- 0805395921. 2. Principles of Genetics, 6th edition (2011), D. Peter Snustad, Michael J. Simmons; John Wiley and Sons, ISBN-13: 978-0470903599. 3. The World of the Cell, 7th edition (2008), Becker, Kleinsmith, Hardin and Bertoni. Benjamin Cummings, ISBN-13: 978-0805393934. 4. Human Molecular Genetics, 3rd edition (2003), Tom Strachan and Andrew Read; Garland Science Publishers, ISBN -13: 978-0815341826. 5. The Cell: A Molecular Approach, 6th edition (2013), Cooper and Hausman; Sinauer Associates, Inc. ISBN-13: 978-1605351551. 6. DNA Replication, 2nd edition (2005), Arthur Kornberg; University Science Books ISBN-13: 978-1891389443. 7. Cell and Molecular Biology: Concepts and Experiments, 7th edition (2013), Gerald Karp; Wiley Publishers, ISBN-13: 978-1118206737. 8. Genomics: The Science and Technology behind the Human Genome Project, 1st edition (1999), Cantor and Smith; John Wiley and Sons, ISBN-13: 978-0471599081. 9. Molecular Cloning: A Laboratory Manual, 4th edition (2012), Michael R. Green and Joseph Sambrook; Cold Spring Harbor Laboratory Press, ISBN-13: 978-1936113422. 10. Concepts of Genetics, 10th edition, (2012). William S. Klug, Michael R. Cummings, Charlotte A. Spencer, Michael A. Palladino. ISBN-13: 978-0321724120. 11. Molecular Biology: Principles and Practice, 1st edition (2012), Cox, Doudna and Donnell, ISBN-13: 978-0-716-7998-8.

BMS D: Human Genetics

Preamble: This course is designed to develop an appreciation for the groundwork carried out so far in order to gain an insight into mechanisms of human genetic diseases, relate to how it has been built on the numerous genetic studies carried out over decades to contribute to the understanding of relationship between genotype and phenotype. The time is poised for understanding human as a model organism. The course will also introduce the methods for whole genome analysis and the genome sequencing.

THEORY Total Lectures: 48

Unit I: History of Human genetics (1 Lecture)

Early Greek concepts about inheritance, Cytogenetics history (the works of Winiwater, Painter and Tjio and Levan), Landmark achievements of Galton, Garrod etc.

Unit II: Patterns of inheritance for monogenic traits (6 Lectures)

Recapitulation of principles of human inheritance pattern through pedigree analysis: Autosomal inheritance-dominant and recessive, Sex-linked inheritance, Sex-limited and Sex- influenced traits, Mitochondrial inheritance. Deviations from the basic pedigree patterns- nonpenetrance, variable expressivity, pleiotropy, late onset, dominance problems, anticipation, genetic heterogeneity and uniparental disomy, mosaicism and chimerism, consanguinity and its effects. Epigenetic modifications and imprinting.

Unit III: Techniques for genomics (6 Lectures)

DNA sequencing (Maxam-Gilbert and Sanger Method, introduction to next generation sequencing), DNA fingerprinting, Polymorphism screening (genotyping of SNPs and microsatellite markers), Expression and proteome analysis (microarray, 2-D analysis, pull down assays).

Unit IV: Mapping strategies (5 Lectures)

Physical maps (different types- restriction, cytogenetic maps, use of FISH in physical mapping, radiation hybrids and clone libraries in STS mapping), Genetic maps. Genetic markers and their applications.

Unit V: Human genome project (4 Lectures)

History, Organization and goals of human genome project, Tools (Vectors- BAC, PAC, YAC and sequencing techniques), Approaches (Hierarchical and shotgun sequencing), Outcomes. Ethical issues and applications in human diseases.

Unit VI: Population genetics (3 Lectures)

Genotypic and allelic frequencies, Linkage disequilibrium, Haplotype construction (two loci using SNPs and/or microsatellites).

Unit VII: Identification of genetic basis of disease (3 Lectures)

Principles. Strategies: positional and candidate gene approaches, positional- cloning approach (examples- HD, CFTR). Concept of twin and adoption studies.

Unit VIII: Prenatal diagnosis (2 Lectures)

Brief introduction, Methods of prenatal diagnosis and its application with example of Aneuploidy and Thalassemia.

Unit IX: Clinical genetics: (4 Lectures)

Inborn errors of metabolism and their genetic basis (example- phenylketonuria), Genetic disorders of haemopoietic systems (examples- sickle cell anemia and thalassemia), Genetic basis of color blindness, Genetic basis of familial cancers (example- retinoblastoma), Genetics of mental retardation.

Unit X: Implications of genome research: (4 Lectures)

Diagnosis and screening of genetic disorders, Prenatal genotyping for mutations in β- globin gene and sickle cell anemia, DNA profiling: establishing identity and relationships, applications in personalized medicine (genetic polymorphism in drug metabolism genes e.g. cytP450 and GST and their effect on drug metabolism and drug response), Genetic counseling.

Unit XI: Guided short project (10 Lectures)

Short project involving, data analysis/in silico analysis of genomes/ literature based project; guiding the students through identification of the project, discussions on approach and methodology, and strategies for data analysis.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. PTC testing to prove monogenic inheritance. 2. Demonstration of DNA fingerprinting. 3. Polymorphism analysis using PCR. 4. Mapping of clones/STS on plasmids or BACs. 5. Video based demonstration of tools for prenatal diagnosis. 6. Haplotype construction. 7. Web based analysis: retrieval of a desired human sequence from NCBI database and sequence alignment using BLAST. 8. Preparation of Human metaphase chromosomes and Giemsa staining.

SUGGESTED READINGS 1. Strachan and Read. Human Molecular Genetics.4th Edition. Garland Science, 2010. ISBN: 978-0815341499. 2. Cantor and Smith. Genomics, 2002, John Wiley and Sons, Inc. ISBN: 9780471599081. 3. J.N. Pasternak. An introduction to Human Molecular Genetics, 2nd Edition, Wiley-Liss, 2005. ISBN: 978-0-471-47426-5. 4. G.N. Wilson. Clinical Genetics: A short Course. Wiley-Liss, 2000. ISBN: 978- 0471298069 5. Vogel and Motulsky, Human Genetics: Problems and Approaches, 3rd Edition, Springer Verlag, 1997. ISBN: 978-3-540-37653-8. 6. T.A. Brown. Genomes, 2nd edition, Oxford: Wiley-Liss; 2002. ISBN-10: 0-471- 25046-5. BMS E: Medical Biochemistry

Preamble: The Medical Biochemistry course has been formulated to impart medically relevant information on clinical biochemistry. Students would learn the principle and applications of the diagnostic enzymology, interplay of hormones in the metabolism and details of various biomolecules of diagnostic significance. These topics are included to educate students on the clinical significance of biochemistry. This course will also focus on the contemporary methods and practical approaches that are used in the clinical laboratories for the investigation of the diseased state

THEORY Total Lectures: 48

Unit I: Basic concepts and scope (01 Lectures)

Unit II: Enzymes: Distribution and diagnostic significance (10 Lectures)

Properties of enzymes used in diagnosis, Factors affecting levels of diagnostic enzymes in blood and the selection of test, Clinical significance of diagnostically important enzymes: creatine kinase, lactate dehydrogenase, alanine- and aspartate aminotransferases, with a detailed account of the biochemical reactions catalysed by these enzymes and of their clinical assays. Kinetic assay and end point assay for the enzymes. Isoenzymes: types of isoenzymes, allozymes, hybrid isoenzymes, isoforms, macrocomplexes, their tissue distribution, clinical and diagnostic significance.

Unit III: Hormones: (06 Lectures)

Classification (with reference to their biochemical nature). Mechanism of action - one example from each class of hormones, with special reference to epinephrine and thyroid hormones (T3 and T4), Functions.

Unit IV: Structural complexities and diseases associated with carbohydrates and lipids (12 Lectures)

Carbohydrates: Sugars as information molecules. Detailed account on Lectins: their role in physiological functions and their potential as drug targets in various infectious diseases. Dietary fibers.

Lipids: Glycerophospholipids, Spingolipids, Types of Lipoproteins (chylomicrons, VLDL, LDL, HDL). Disorders associated with lipoprotein metabolism (hypercholesterolemia). Prostaglandins: classification, biosynthesis, role of COX-1, COX-2, NSAIDS in synthesis, functions. Steroids: Cholesterol- biosynthesis and regulation, inhibitors of cholesterol biosynthesis (Statins - structure and biochemical basis). Unit V: Vitamins (8 Lectures) Definition, classification, functions, recommended dietary allowances, and dietary precursors. Diseases due to deficiency of water-soluble and fat-soluble vitamins: symptoms and clinical significance.

Unit VI: An overview of integrative metabolism (11 Lectures)

Local and global regulation in tissue specific metabolism. Interplay of insulin and glucagon. Integration of various metabolic pathways of proteins, lipids, carbohydrates and nucleic acids. Obesity, Role of leptin, ghrelin and other hormones in regulation of body mass.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Preparation of serum and plasma from whole blood. 2. Quantitative determination of the following in the whole blood/plasma/serum: a) LFT: i) SGPT or SGOT ii) Albumin/Total protein b) KFT: i) Urea ii) Uric acid c) Metabolites: i) Total cholesterol, HDL, LDL and triglycerides ii) Serum protein A: G ratio. iii) Serum glucose. 3. Five case studies based on above quantitative estimations performed.

SUGGESTED READINGS 1. Tietz Fundamentals of Clinical Chemistry, 6th edition (2007), Carl A. Burtis, Edward R. Ashwood, and David E. Bruns;WB Saunders Co, ISBN-13: 978-0721638652. 2. Harpers Illustrated Biochemistry, 29th edition (2012), Robert Murray, David Bender, Kathleen M. Botham Peter J. Kennelly, Victor Rodwell, P. Anthony Weil; McGraw-Hill Medical, ISBN-13: 978-0071765763 3. Lehninger‟s Principles of Biochemistry, David L. Nelson and Michael M. Cox, 5th edition(2008), ISBN-13: 978-0716771081 4. Textbook of Medical Biochemistry, 7thedition (2007), Chatterjea&Shinde, Jaypee Publications, ISBN: 81-8448-134-9. 5. Biochemistry, J. M. Berg, J. L. Tymoczko and L. Stryer, 6th edition (2006), W. H. Freeman and Co. ISBN-13: 978-0716787242 6. Fundamentals of Biochemistry: Life at the Molecular Level, 4th edition (2012), Donald Voet, Judith G. Voet, Charlotte W. Pratt; Wiley, ISBN-13: 978-0470547847

BMS F: Medical Biotechnology

Preamble: The unique preposition of this paper is that the students learn the basic techniques and methods used in the diagnosis and therapy of various human diseases and in the production of biopharmaceuticals. The concepts of cloning and expression of the desired gene is explored. This paper aims to train students to understand how biological systems are applied in the advancement of medical biotechnology.

THEORY Total Lectures: 48

Unit I: Introduction to Biotechnology (1 Lecture) Brief history and Importance, Emergence of molecular biotechnology, Concept of in vivo and in vitro gene cloning.

Unit II: Techniques (4 Lectures)

Northern hybridization, Microarray concept for studying transcriptomes, Electroporation, Transformation, Use of enzymatic and chemi-luminiscent methods for detection of proteins, Preparation of labelled probes.

Unit III: Manipulation of the purified DNA (4 Lectures)

Restriction and modification system: Type I-IV restriction endonucleases, nomenclature and sequence recognition, isochizomers, blunt end and sticky ends, restriction mapping. Joining of DNA molecules: role of DNA ligase enzymes, adaptors, linkers, homopolymer tailing.

Unit IV: Cloning vectors (7 Lectures)

Basic biology of plasmids, Cloning vectors (pUC vectors, T-vectors), Lambda phage-derived vectors (replacement and insertion vectors), Cosmids, in vitro packaging, Cloning vectors for eukaryotic system, Expression vectors, Prokaryotic and Eukaryotic expression vectors with one example each, Shuttle vectors, Inducible and Constitutive expression.

Unit V: Cloning and expression of genes in Prokaryotic and Eukaryotic cells (8 Lectures)

Process of gene cloning, Expression and Purification, Methods for clone identification, Selection (antibiotic selection) and Screening (blue/white & by colony PCR) of bacterial transformants. Challenges in expression of foreign proteins in heterologous host, Factors affecting the expression host cell physiology. Promoters, Codon usage, Plasmid copy number. Expression in eukaryotic cells (yeast), Fusion proteins and tags, Fusion and tagged protein cleavage system, Manipulations to improve the yield of recombinant protein.

Unit VI: Polymerase chain reaction (PCR) (4 Lectures)

Principle and applications, Primer-designing, different types of PCR: Hot start, Reverse transcription, Real time and multiplex PCR.

Unit VII. Studying gene expression and function and genomes (6 Lectures)

RNA transcript of the gene analysis by primer extension and PCR, Identification of protein binding sites: gel retardation, foot printing and modification interference assays. Deletion assays, Phage display and Yeast two hybrid system for studying protein-protein interaction.

Unit VIII. Directed mutagenesis and protein engineering (4 Lectures)

Oligonucleotide-directed mutagenesis, PCR-based method of mutagenesis, Screening and identification of mutants. Protein engineering: addition of disulphide bonds, amino acid substitution. Subtilisin and alpha-Antitrypsin (AAT) as the examples of mutant enzymes and their applications.

Unit IX: Application of Medical Biotechnology (8 Lectures)

(a) Production of recombinant biomolecules: Insulin, Adenosine deaminase (ADA), Factor VIII and Interferons. (b) DNA Profiling: Introduction, DNA profiling based on STRs, minisatellites, RFLP, AFLP, VNTRs, SNPs and their applications. (c) Gene Therapy: Strategies and limitations, Somatic and Germline gene therapy, Vectors used in gene therapy (viral and non-viral) and their comparison. Treatment for genetic and infectious diseases (one example each).

Unit X: Biosafety and ethical issues in biotechnology (2 Lectures)

Safe handling and disposal of GMOs and toxic reagents. Concerns about gene editing, gene therapy and impact of GMOs on the environment.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Regular maintenance and storage of E. coli DH5 alpha cells. 2. Preparation of competent cells (E.coli) by Calcium chloride method. 3. Digestion of plasmid DNA with different Type II restriction endonucleases. 4. PCR amplification of the desired gene, followed by restriction digestion. 5. DNA extraction from gel 6. Ligation of the insert to the vector using T4 DNA ligase. 7. Agarose gel analysis of restricted and ligated DNA. 8. Transform competent bacterial cells with recombinant DNA. 9. Identification of recombinants by blue-white screening and PCR. 10. Over-expression of recombinant proteins in bacteria, followed by detection by SDS-PAGE. SUGGESTED READINGS 1. Gene cloning and DNA analysis, 6th edition (2010), T.A. Brown. Wiley-Blackwell ISBN-13: 978-1405181730. 2. Principles of Gene Manipulation and Genomics, 7th edition (2006), S.B. Primrose and R.M. Twyman. Blackwell Scientific ISBN: 978-1405135443. 3. Molecular Biotechnology: Principles and Applications of Recombinant DNA, 4th edition (2009), Bernard R. Glick, Jack J. Pasternack, Cheryl I. Patten. ASM press, ISBN- 13:9781555814984. 4. DNA Replication, 2nd edition (1992), Arthur Kornberg; University Science Books, ISBN - 13:978- 0716720034. 5. Genomics: The Science and Technology behind the Human Genome Project, 1st edition (1999), Cantor and Smith; John Wiley and Sons, ISBN-13:978-0471599081. 6. Molecular Cloning: A Laboratory Manual, 4th edition (2012), Three-volume set by Michael R. Green, Joseph Sambrook; Cold Spring Harbor Laboratory Press, ISBN-13: 978- 1936113422.

Generic Elective (GE) Courses

B.Sc. (Hons) Course in Biomedical Science

GE: Generic Elective Courses

BMS-G1: Basics of Immunology

BMS-G2: Biosafety and Bioethics

BMS-G3: Biostatistics

BMS-G4: Bridging Information Technology and Biotechnology

BMS-G5: Concepts in Biotechnology

BMS-G6: Concepts in Medicinal Chemistry and Drug Development

BMS-G7: Introduction to Bioorganic Chemistry

BMS-G8: Pathological Basis of Diseases

BMS-G9: Pharmacology and Toxicology

BMS-G10: Tools and Model organisms in Biomedical Research

In alphabetical order

*(Wherever wet lab experiments are not possible the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

BMS-G1: Basics of Immunology

Preamble: Immunology is the study that helps us to distinguish between self and non-self molecules and how our immune system mediates protection against attack by potentially infectious organisms. Malfunctioning of the immune system leads to a number of disorders and diseases. Understanding the biology of the immune system is, therefore, key to developing strategies towards prevention and cure to a number of disorders and diseases that result due to interference in the functioning and regulation of the immune system. This paper elaborates the functional interrelationships of primary and secondary lymphoid organs and the residing cells, their function and regulation by the immune system.

THEORY Total Lectures: 48

Unit I: Overview (02 Lectures)

Historical background, General concepts of the immune system, Innate and Adaptive immunity. Active and Passive immunity. Primary and Secondary immune response.

Unit II: Our immune system (10 Lectures)

(a) T and B lymphocyte, NK cells, monocytes and macrophages; neutrophils, eosinophils, basophils, mast cells and dendritic cells. Thymus and bone marrow. Lymph nodes, Spleen. (b) General overview of the complement system: Components of the complement activation (classical pathway),Biological consequence of complement activation.

Unit III: Immune response (20 Lectures)

(a) Antigens and haptens: Properties (foreignness, molecular size) and their importance in cell mediated and humoral immune response. (b) Humoral immune response: Concepts of B cell development in bone marrow, Generation of plasma cells and memory B cells in lymphoid organs. Antibodies: Historical perspective of antibody structure, structure, function and properties of the antibodies, different classes and subclasses and biological activities of antibodies, Hybridoma technology and Monoclonal antibodies. (c) Cell mediated immune response: T cell maturation in thymus (in brief), Thymic selection, Self MHC restriction of T cells, T cell sub-types and their effector functions. Molecules involved in functioning of T cells-Trimolecular complex formation between APC and Naïve T cells, Properties and functions of Interferon (IFN-γ) and Interleukins (IL4). (d) Basic introduction to Major Histocompatibility Complex: Organization of MHC and inheritance in human.

Unit IV: Antigen-antibody interactions based immunological techniques (8 Lectures)

Concept of affinity and Avidity, cross reactivity, precipitation, agglutination, immunodiffusion, ELISA.

Unit V: Vaccines (4 Lectures) Concept and history of vaccines, contribution of Edward Jenner, Components of vaccines (eg. BCG vaccine), Overview of National Immunization Course.

Unit VI: Dysfunctions of immune system (4 Lectures)

Types of hypersensitivity, Overview of autoimmunity. Immunodeficiency disorders: Animal models of primary immunodeficiency (nude mouse and SCID mouse).

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. To perform immuno-diffusion by Ouchterlony method. 2. Immuno-diffusion by Mancini method 3. To perform ELISA experiment. 4. To perform Agglutination inhibition Assay 5. To perform sandwich dot ELISA. 6. To perform blood grouping (direct agglutination) or Widal test (indirect agglutination).

SUGGESTED READINGS 1. Immunology, 6th edition, (2006), J. Kuby et al, W.H. Freeman and Company, New York. ISBN-13: 978-1429202114. 2. Microbiology, 7th edition, (2008), Prescott, L., John Ii Harley, Donald A. Klein, McGraw Hill. ISBN-13: 978-0071102315.

BMS-G2: Biosafety and Bioethics

Preamble: The recent advances in the field of biotechnology have brought into focus several safety and ethical issues. The inventions in the field of genetic engineering and related fields of molecular biology not only affect us but also the plants, microflora, animals and the entire environment and the way we practice agriculture, medicine and food processing. An increase in our ability to change life forms in recent years has given rise to the new science of bioethics. The present course focus on the biosafety and bioethical issues the modern society confronts. Topics such as biosafety levels, GM food debate, impact of biotechnology on biosafety, biotech products and ethical issues, governance of biosafety, environmentally responsible use of biotechnology, clinical ethics will be discussed in the curriculum.

THEORY Total Lectures: 48

Unit I: Introduction (03 Lectures)

Historical background, Introduction to biological safety cabinets, Primary containment for biohazards, Biosafety levels of specific microorganisms, Recommended biosafety levels for infectious agents and infected animals.

Unit II: Biosafety guidelines (10 Lectures)

Government of India definition of genetic modified organism (GMOs) and living modified organisms (LMOs), Roles of institutional biosafety committee, review committee on genetic manipulation (RCGM), genetic engineering approval committee (GEAC) for GMO applications in food and agriculture, environmental release of GMOs. The GM-food debate and biosafety assessment procedures for biotech foods and related products, including transgenic food crops, case studies of relevance. Biosafety assessment of pharmaceutical products such as drugs/vaccines etc.

Unit III: Handling and transportation of GM, infectious and radioactive materials (05 Lectures) Risk analysis, risk assessment, risk management and communication, Overview of national regulations and relevant international agreements including Cartagena Protocol.

Unit IV: Biosafety management (06 Lectures)

Key to the environmentally responsible use of biotechnology, Ethical implications of biotechnological products and techniques, Social and ethical implications of biological weapons.

Unit V: Concept of social science (02 Lectures)

Reason to apply its principles to study cause of health problems and suggest appropriate intervention/ solution to problem.

Unit VI: Foundation of bioethics (02Lectures)

Definition, Historic evolution, Codes and guidelines, Universal principles.

Unit VII: Codes, covenants, declarations and guidelines (05 Lectures)

Define the term “Bioethics” in relation to profession, society, and biomedicine, Learn about gradation of moral and ethical norms from simpler to higher levels for initiating right actions to “first do no harm” and learn about prayers, oaths, covenants, declarations, guidelines and codes which have relevance to bioethics.

Unit VIII: Clinical ethics (02 Lectures)

Describe the sanctity of human life and the need to preserve human life. Explain about issues related to prenatal screening, clinical trials (Phase I/II/III/IV) studies.

Unit IX: Women health ethics (03Lectures)

Vulnerability of women with respect to health care, Examination and screening of women for disease, Social issues like domestic violence, female genital mutilation and abortion.

Unit X: Medical errors and negligence (03 Lectures)

Medical error and medical negligence difference, Remedies against medical negligence, Protection and compensation related to it.

Unit XI: Critical care ethics (04 Lectures)

History and need for ICU care, Functioning and ethical principles of an ICU care, Triage and futility, End of life care: ethical principles related to withholding treatment and withdrawing treatment (euthanasia), L.6+egal position regarding policies in ICU and handling of conflicts in the ICU.

Unit XII: Care in HIV and AIDS (02 Lectures)

Basics of HIV infection, Identify ethical issues in clinical practice of HIV medicine and its prevention, Research ethics related to HIV.

Unit XIII: Ethical use of animals in the laboratory (01 Lecture) PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. A case study based on genetic modified organism (Bt-Cotton). 2. A case study based on genetic modified organism (Bt-Brinjal). 3. A case study based on terminator seeds. 4. A case study based on removal of selective marker in a DNA vaccine. 5. A case study on clinical trials of drugs in India with emphasis on ethical issues. 6. A case study on women health ethics. 7. A case study on medical errors and negligence. 8. A case study on critical care ethics. 9. A case study on ethical issues in clinical practice of AIDS. 10. A case study on handling and disposal of radioactive waste.

SUGGESTED READINGS 1. Bioethics and Biosafety, 1st edition (2008), M. K Sateesh, I K International Pvt Ltd, ISBN- 13: 978-8190675703. 2. The Cambridge Textbook of Bioethics, 1st edition (2008), Peter A. Singer and A. M. Viens; Cambridge University Press, ISBN-13: 978-0511545566. 3. Foundation of Bioethics, 2nd edition (1996), E. H Tristram; Oxford University Press, ISBN- 13: 9780195057362. 4. Social science: An introduction to the study of society, 14th edition (2010), Hunt, E. F.,and Colander, D. C. ; Peason/Allyn and Bacon, Boston, ISBN-13: 978-020570271. 5. Principles of Biomedical Ethics, 6th edition (2011), Beauchamp Tl, Childress JF; Oxford University Press, 2001. ISBN-13: 978-0195143317. 6. A Companion to Bioethics, 2nd edition (2012), Helga Kuhse, Peter Singer; John Wiley and Sons, ISBN-13: 978-1444350845. 7. Bioethics: An Introduction to the History, Methods, and Practice, 1st edition (1997), Nancy Ann Silbergeld Jecker, Albert R. Jonsen, Robert A. Pearlman; Jones and Bartlett Learning, ISBN-13: 978-0763702281. 8. Genetically Modified Organisms and biosafety, 1st edition (2004), Tomme Young. ISBN- 13: 978-2831707983. 9. Environmental Safety of Genetically Engineered Crops, 1st edition (2011), Rebecca Grumet, James F. Hancock, Karim M. Maredia, CholaniWeebadde, Michigan State University Press ISBN-13: 978-1611860085. 10. Biosafety and Bioethics, 1st edition (2006), Rajmohan Joshi; Isha Books ISBN-13: 978- 8182053779. 11. Bioethics and biosafety in biotechnology, 1st edition (2007), V. Sreekrishna; New Age International (P) Ltd., ISBN-13: 978-8122420852.

BMS-G3: Biostatistics

Preamble: The objective of this course is to acknowledge, appreciate and effectively incorporate the basic statistical concepts indispensable for carrying out and understanding biological hypothesis, experimentation as well as validations. It is aimed at creating awareness about the applications of statistics in biological sciences along with building confidence in students to logically test their experimental data with an appropriate set of test of significance. Use of open source software and web material is encouraged as the course intends to give wings to the students and not just the height for their soaring potentials!

THEORY Total Lectures: 48

Unit I: Descriptive statistics (13 lectures)

a) Data in biology: Development in biostatistics, Samples and Populations, Techniques of sampling (random and stratified), Sampling and non-sampling errors, Variables in biology, Univariate and bivariate frequency distributions and their graphical representations. b) Measures of central tendency: Arithmetic mean, mode, median and partition values. c) Measures of dispersion: Range, standard deviation, coefficient of variance and covariance. d) Measures of skewness: Pearson‟s coefficient of skewness. e) Kurtosis.

Unit II: Probability and probability distributions (15 lectures)

a) Probability: Basic concepts, Addition and Multiplication rules of probability, Conditional probability, Bayes‟ theorem and its applications in biostatistics. b) Random variables: Discrete and Continuous. c) Mathematical Expectation and Variance: Definition and Properties. d) Probability Distributions: Binomial distribution, Poisson distribution and Normal distribution along with their properties and relationships.

Unit III: Correlation and linear regression (05 lectures)

a) Correlation Analysis: Scatter diagrams, Pearson‟s and Spearman‟s coefficients of correlation, Coefficient of determination. b) Regression Analysis: Method of least squares, Equations of lines of regression and their applications in biostatistics.

Unit IV: Hypothesis testing: (15 lectures)

a) Sampling distributions and standard error, Null and Alternate hypothesis, Basic concept and illustrations of type I and type II errors, Concept of confidence interval estimation. b) Large sample tests for single mean and difference of means. c) Student‟s t-distribution: test for single mean, difference of means and paired t- test. Chi- square distribution: tests for goodness of fit, independence of attributes and homogeneity. F-distribution, one-way and two-way analysis of variance (ANOVA). d) Non-parametric analysis: Sign and run tests.

PRACTICALS Computer-based practicals using any statistical software like 'R'. MATLAB, SPSS, Spreadsheets, etc. to understand the following concepts:

1. Graphical data representation 2. Measures of central tendency and dispersion 3. Probability and probability distributions: binomial, Poisson and normal distribution 4. Correlation and linear regression analysis 5. Student‟s t- test 6. Chi-square test 7. ANOVA

SUGGESTED READINGS 1. Primer of Biostatistics, 7th edition (2011), Stanton Glantz, McGraw-Hill Medical. ISBN- 13: 978-0071781503. 2. Biostatistics: A Foundation for Analysis in the Health Sciences, 10th edition (2013), Wayne W Daniel and Chad L. Cross, Wiley. ISBN-13: 978-1118302798. 3. Principles of Biostatistics, 2nd edition (2000), Marcello Pagano and KimberleeGauvrean, Thompson learning. ISBN-13: 978-0534229023. 4. Biostatistical Analysis, 5th edition (2009), Jerrold H. Zar, Pearson. ISBN-13: 978- 0131008465.

BMS-G4: Bridging Information Technology and Biotechnology

Preamble: This course has been designed to reflect how information technology synergizes biotechnology. The course will focus on information retrieval from various databases, the basis of sequence data analysis, use of Hidden Markov Model to solve various sequence analysis problems, such as pairwise and multiple sequence alignments, gene annotation etc.

THEORY Total Lectures: 48 Unit I: Convergence of biotechnology and information technology (02 Lectures)

Introduction to bioinformatics and its applications, Internet and bioinformatics.

Unit II: Databases and genome browsers (08 Lectures)

Unit III: Sequence alignment and visualization (08 Lectures)

Local and global sequence alignments (Needleman-Wunsch and Smith-Waterman algorithms), pair-wise (BLAST and FASTA algorithms) and multiple sequence alignment (Clustal W) and its importance.

Unit IV: Theory behind BLAST (04 Lectures)

How Hidden Markov Model (HMM) can be used to model a family of unaligned sequences or a common motif within a set of unaligned sequences and further be used for discrimination and multiple alignment.

Unit V: Phylogenetic analysis (05 Lectures)

Basics and tools for phylogenetic analysis, Cladistics and its assumptions, Tree-building methods (Character and distance based methods), Construction of phylogenetic trees (PHYLIP).

Unit VI: Gene ontology (03 Lectures)

The Ontologies: Cellular component, Biological process and Molecular function.

Unit VII: Genome analysis (05 Lectures)

Features of DNA sequence analysis, Gene prediction methods, SNP analysis (dbSNP), Sequence assembly and genome annotation.

Unit VIII: Restriction site mapping and primer design (06 Lectures)

In silico restriction mapping, Cloning and expression, Identification of cDNA from databases, Design of primers for standard and real time PCR, e-PCR.

Unit IX: Introduction to machine learning (04 Lectures)

Learning from data, How can we extract knowledge from data to take decisions and program the computer to be able to learn from examples and adapt systems dynamically to enable better user experiences.

Unit X: Application of bioinformatics in biotechnology (03 Lectures)

PCR diagnostic design, Design strategy for over-expression of a therapeutic protein using specific examples to illustrate the strategy.

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Retrieval of information from nucleotide databases. 2. Sequence alignment using BLAST. 3. Multiple sequence alignment using Clustal W. 4. Phylogenetic analysis using PHYLIP 5. Gene Ontology 6. Gene prediction and ORF finding. 7. In silico primer designing for standard and real time PCR and performing e-PCR.

BMS-G5: Concepts in Biotechnology

Preamble: The preposition of this paper is that the students learn the basic techniques and methods used in biotechnology. This paper aims to train students to understand how biological systems are manipulated and applied in the advancement of biotechnology.

THEORY Total Lectures: 48

Unit I: Introduction (1 Lecture)

Brief history and importance.

Unit II: Basic techniques (6 Lectures)

Isolation and purification of genomic and plasmid DNA, Agarose and polyacrylamide gel electrophoresis, Southern and Western hybridization (probes and labels used in the preparation of probes- radioactive, fluorescent, enzymatic and chemi-luminiscent).

Unit III: DNA modification (5 Lectures)

Restriction endonucleases: Restriction and modification systems, nomenclature and types of restriction enzymes (type I-IV), recognition of restriction sites, restriction mapping.

Joining of DNA molecules: sticky end and blunt end ligations, role of DNA ligase, reaction mechanism of ligation in viruses and bacteria, adaptors, linkers, homopolymer tailing.

Unit IV: Cloning (10 Lectures)

Vectors: Plasmids (pUC vectors), Bacteriophage (lambda phage-derived replacement and insertion vectors), Cosmids, in vitro packaging; expression vectors (one example each of prokaryotic and eukaryotic expression vectors); shuttle vectors.

Bacterial transformation, selection (antibiotic selection methods) and screening (blue/white) of transformants. Challenges in expression of eukaryotic proteins in prokaryotic hosts, factors affecting the expression, expression in eukaryotic cells, cDNA cloning.

Unit V: Polymerase chain reaction and Sequencing of DNA (10 Lectures)

Polymerase Chain Reaction (PCR): Principle, types of DNA polymerases, primer designing, types of PCR: hot start, multiplex, inverse, reverse transcription and touchdown PCR and their applications.

Sequencing: Chemical (Maxam Gilbert) and Enzymatic (Sanger‟s dideoxy) method, automated DNA sequencing concept.

Unit VI: DNA Profiling (4 Lectures)

Restriction Fragment Length Polymorphism (RFLP), Amplified Fragment Length Polymorphism (AFLP), Short Tandem Repeats (STRs), Variable Number Tandem Repeats (VNTR), Single Nucleotide Polymorphisms (SNP) and their applications in forensic science. Unit VII: Genomic and cDNA libraries (5 Lectures)

Construction of genomic and cDNA libraries, their screening by nucleic acid hybridization (Colony and Plaque hybridization) and immunochemical methods.

Unit VIII: Application of Biotechnology (5 Lectures)

Protein engineering concept and examples of Subtilisin. Production of recombinant biomolecules: Insulin, Somatostatin, Gene Therapy: Strategies and limitations in the treatment of genetic and infectious diseases, somatic and germline gene therapy, any two examples of viral and non-viral vectors used in gene therapy.

Unit IX: Biosafety and ethical issues (2 Lectures)

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. To prepare general media and reagents. 2. To perform genomic DNA isolation. 3. To perform plasmid DNA isolation. 4. To perform agarose gel electrophoresis. 5. To amplify DNA using PCR. 6. To perform restriction digestion of plasmid DNA. 7. To analyze DNA sequence from autoradiogram/ electrophoretogram.

SUGGESTED READINGS

1. Gene cloning and DNA analysis, 6th edition (2010), T.A. Brown. Wiley- Blackwell ISBN-13: 978-1405181730. 2. Principles of Gene Manipulation and Genomics, 7th edition (2006), S.B. Primrose and R.M. Twyman. Blackwell Scientific ISBN: 978-1405135443. 3. Molecular Biotechnology: Principles and Applications of Recombinant DNA, 4th edition (2009),Bernard R. Glick, Jack J. Paternack, Cheryl I. Patten. ASM press, ISBN- 13:9781555814984. 4. DNA Replication, 2nd edition (1992), Arthur Kornberg; University Science Books, ISBN -13:978-0716720034. 5. Genomics: The Science and Technology behind the Human Genome Project, 1st edition (1999), Cantor and Smith; John Wiley and Sons, ISBN-13:978-0471599081. 6. Molecular Cloning: A Laboratory Manual, 4th edition (2012), Three-volume set by Michael R. Green, Joseph Sambrook; Cold Spring Harbor Laboratory Press, ISBN-13: 978-1936113422. BMS-G6: Concepts in Medicinal Chemistry and Drug Development

Preamble: The course emphasizes on various drug targets in the body and highlights the importance of drug-receptor interactions, lead discovery, drug design and drug development strategies.

THEORY Total Lectures: 48

Unit I: General introduction (02 Lectures)

Definition and scope of drug design.

Unit II: Drug target classification (08 Lectures)

Proteins as drug targets: Receptors - receptor role, Ion channels, Membrane bound enzyme activation, Agonist and antagonists, Concept of inverse agonist, Dsensitization and sensitization of receptors, Affinity, Efficacy and potency. Enzymes: Enzyme inhibitors (competitive, non- competitive, suicide inhibitors), Medicinal use of enzyme inhibitors. Nucleic acids as drug targets: Classes of drugs that interact with DNA: DNA intercalators and DNA alkylators.

Unit III: Physicochemical principles of drug action (08 Lectures)

Partition coefficient, Drug dissolution, Acid-base properties, Surface activity, Bioavailablity, Stereochemical aspects of drug action.

Unit IV: Drug receptor interactions (08 Lectures)

Kinetic analysis of ligand receptor interactions using scatchard plot, Double reciprocal plot, Hill plot, Forces involved, Relationship between dose and effect (graded and quantal response).

Unit V: Principles of drug design (08 Lectures)

Introduction to SAR, Strategies in the search for new lead compounds, Analogue synthesis versus rational drug design, Concept of prodrugs.

Unit VI: Drug discovery and pharmainformatics (14 Lectures)

Drug discovery pipeline, Drug target identification and validation for microbial pathogen, Selection of gene unique to the pathogen, screening for its presence in other microbes and human host. Drug Databases, PubChem, Calculating drug-like properties, Introduction to rational drug design methods, Optimization of lead compounds, Protein 3D structure and binding site analysis, Similarity based virtual screening using online tools.

PRACTICALS (Any 6) (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Recrystallization of organic compound, determination of its melting point and TLC. 2. Preparation of Benzocaine. 3. Determination of partition coefficient of Aspirin in octanol-water system. 4. Preparation of Phenacetin. 5. Visualization and analysis of 3D structures of proteins. 6. Finding the active sites in a receptor. 7. Molecular docking using AutoDock or HEX. 8. Searching databases for drug like compounds and computing drug like properties of small molecules. 9. Extraction of piperine from black pepper.

BMS-G7: Introduction to Bioorganic Chemistry

Preamble: Bioorganic Chemistry integrates the fundamental principles of chemistry with biology. It aims to apply the tools of chemistry in understanding the molecular structure of biomolecules and the chemical reactions occurring in biological processes. It has been structured to understand the significance of acids and bases in the formation of the buffers and maintenance of pH in the cell. The course helps to understand the interaction of various organic and inorganic biomolecules to form ionic and covalent bonds. The inclusion of stereochemistry and molecular interactions explains the 3D structure and stability of biomolecules.

THEORY Total Lectures: 48

Unit I: Ionic equilibria (12 Lectures)

Strong, moderate and weak electrolytes, Degree of ionization, Factors affecting degree of ionization, Ionization constant and ionic product of water. Ionization of weak acids and bases(concept of pKa), pH scale and effect of pH on the structure of biomolecules. Common ion effect. Buffer solutions and its action. Henderson-Hasselbach equation, buffering zone, buffer index. Qualitative treatment of acid base titration curves (NaOH vs HCl, mono amino acid), Isoelectric point, Concept of pI and zwitter ion.

Unit II: Application of chemical bonding and molecular structure in biomolecules (08 Lectures) Ionic Bonding: General characteristics of ionic bonding. Lattice energy and solvation energy and their importance in the context of stability and solubility of ionic compounds. Polarizing power and polarizability, Fajan‟s rules, ionic character in covalent compounds. Covalent bonding: Shapes of some inorganic molecules and ions on the basis of VSEPR with suitable examples of linear, trigonal planar, square planar, tetrahedral, trigonal bipyramidal and octahedral arrangements. Hybridization(concept only). Coordinate bonding: Introduction, Structure of biomolecules- Haemoglobin.

Unit III: Fundamentals of Organic Chemistry (10 Lectures)

Concept of hybridization of carbon. Cleavage of a covalent bond: homolysis and heterolysis. Electronic effects and their applications (inductive, electromeric, hyperconjugation and resonance). Structure and stability of reactive intermediates (carbocations, carbanions and free radicals). Relative acid strength: carboxylic acids (aliphatic, aromatic and halo- substituted aliphatic). Relative basic strength of amines (aliphatic). Intermolecular and intramolecular forces, Types of intermolecular forces and their characteristics-ion-dipole, dipole-dipole, dipole-induced dipole and dispersion forces. Intermolecular and intramolecular hydrogen bonding. Effect of intermolecular and intramolecular forces on properties such as solubility, vapour pressure, melting and boiling points of organic compounds and effect of inter/intra-molecular forces on structure of different biomolecules-peptides and nucleotides.

Unit IV: Stereochemistry (10 Lectures)

Conformations w.r.t. ethane, butane, angle strain, Interconversion of Wedge Formula, Newman, Sawhorse and Fischer representations. Concept of chirality (upto two carbon atoms). Configuration: Geometrical- cis - trans nomenclature. CIP Rules and E / Z Nomenclature (for upto two C=C systems), Threo and erythro, Optical isomerism (Enantiomerism, Diastereomerism and Meso compounds), R/ S (for upto 2 chiral carbon atoms). D and L nomenclature, General Properties of Glucose and Fructose (open chain and cyclic structure- Haworth projection), configuration and absolute configuration of Glucose and Fructose , Mutarotation, epimers, anomers (Glycosidic linkage, reducing and non-reducing sugars).

Unit V: Reaction Mechanism and name reactions (8 Lectures)

Addition Reactions: Hydrohalogenation (Markovnikov‟s and Anti- markovnikov‟s addition). Nucleophilic substitution reactions: mechanism of SN1 and SN2 reactions, Walden inversion. Electrophilic Substitution Reactions (aromatic compounds): General mechanism of electrophilic substitution reactions (nitration, halogenation, sulphonation). Biologically significant name reactions: Aldol (Glucogenesis), Retro-aldol (Glycocolysis), Benzoin condesation (umpolung-decarboxylation of pyruvate in the presence of TPP), Knoevenagel (Application in drug synthesis), Cannizzaro and Cross Cannizzaro (Sugar metabolism), Baeyer Villiger reaction (FAD dependent ketone synthesis), Pinacole- pinacolone rearrangement (1,2-carbon carbon shift).

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Preparation of solutions based on molarity, normality, percentage, dilutions etc. 2. Preparation of buffers. 3. Estimation of Mohr‟s salt/ oxalic acid by titrating with KMNO4. 4. Estimation of Cu (II) ions iodometrically using Na2S2O3. 5. Qualitative tests for carbohydrates to identify the given unknown carbohydrate solution: Mohlisch, Barfoed, Fehling/ Tollen/ Benedict, Selvinoff, Osazone, Bial‟stests. 5. To determine the optical rotation of a biomolecule. 6. To find pKa value of given acetic acid/ amino acid. 7. Absorption spectrum of DNA/ Protein 8. Estimation of (i) Mg2+ or (ii) Zn2+ by complexometric titration using EDTA SUGGESTED READINGS 1. Concise Inorganic Chemistry, 5th edition (1999), J. D. Lee; Wiley-Blackwell, ISBN-13: 9780632052936. 2. Organic Chemistry, 6th edition (1996), I L Finar ( volume I and II); ELBS, Longman Higher Education. ISBN-13: 978-0582305601. 3. Barrow, G. M. Physical Chemistry Tata McGraw-Hill (2007). ISBN 13, 780074620311. 4. Castellan, G. W. Physical Chemistry 4th Ed. Narosa (2004). ISBN 978-81-85015-59-0. 5. T. W. Graham Solomons: Organic Chemistry, John Wiley and Sons. ISBN-13: 9781118147900. 6. L. Eliel: Stereochemistry of Carbon Compounds, Tata McGraw Hill. ISBN 13 – 9780 070992900. 7. Organic Chemistry, 6th edition (1992), R. T. Morrison and R. N. Boyd; Pearson Education. ISBN-13: 9780136436690. 8. Bioorganic Chemistry, 3rd edition (1999), Hermann Dugas; Springer Verlag. ISBN-13: 978- 0387989105. 9. Atkins, P.W. & Paula, J. Physical Chemistry, Oxford Press, 2006. ISBN: 0716787598. 10. Huheey, J.E. Inorganic Chemistry, Prentice Hall 1993. ISBN: 0-06-642995-X. 11. Vogel‟s Quantitative Inorganic Analysis, A.I. Vogel, Prentice Hall, 6th Edition. ISBN13: 978-0582226289. 12. Senior practical Physical Chemistry, B.D. Khosla, R. Chand & Co. ISBN-13: 9788180450792 13. An Introduction to Practical Biochemistry, 3rd edition (1987), Plummer, McGraw-Hill College; ISBN-13: 978-0070841659 BMS-G8: Pathological basis of diseases

Preamble: Claude Bernard once said, “Effects vary with the conditions which bring them to pass, but laws do not vary. Physiology and pathology states are ruled by the same forces; they differ only because of the special conditions under which the vital laws manifest themselves”. Thus the syllabi of Pathology compliments and supplements the necessary knowledge students have gained in Physiology. Consequently it incorporates topics like cellular adaptations, inflammation, neoplasia, cellular ageing and other infectious diseases. Pathology also provides the necessary inputs for the other disciplines like Pharmacology, social and preventive medicine, medicinal biochemistry etc. All the topics and experiments are introductory in nature and lay stress on introducing Students with basic concepts of pathology

THEORY Total Lectures: 48

Unit I: Introduction (5 Lectures)

History of pathology, Basic definitions and common terms used in pathology, Basic Concepts in cell and tissue organization.

Unit II: Basis of Pathogenesis: Cell Injury and responses of cells to injury (6 Lectures)

An overview of cellular adaptation: Hyperplasia, Hypertrophy, Atrophy, Metaplasia. Causes and mechanisms of cell injury, reversible and irreversible injury, Necrosis, Apoptosis, Types of apoptosis, Intracellular accumulations, Cellular ageing and its mechanisms, Fibrosis.

Unit III: Basis of Pathogenesis: Inflammation (8 Lectures)

Basic concepts of acute and chronic inflammation: Vascular Changes, cellular events, important chemical mediators of inflammation, Morphological effects of inflammation response, Granulomatous Inflammation.

Unit IV: Basis of Pathogenesis: Hemodynamic derangements (6 Lectures)

An overview of edema, hyperemia, congestion, hemorrhage, hemostasis and thrombosis. Embolism, Infarction and shock with suitable examples.

Unit V: Tissue regeneration and repair (4 Lectures)

Mechanism of tissue regeneration, Role of ECM, Repair by healing, scar formation, cutaneous wound healing. Tissue remodeling in liver (mechanism of fibrosis and cirrhosis).

Unit VI: Tumor Pathology (7 Lectures)

Definitions, Nomenclature, Characteristics of benign and malignant neoplasms, Grading and staging of cancer, Biology of tumor growth, Invasion and metastasis, Carcinogens and cancer, Concept of oncogenes, Tumor suppressor genes, DNA repair genes, Cancer stem cells.

Unit VII: Infectious diseases Pathology (12 Lectures)

A. Etiology and pathophysiology of Lifestyle diseases: Diabetes, Atherosclerosis and Myocardial infarction. B. Etiology and Pathophysiology of Infectious diseases: Diarrheal diseases like Cholera, Tuberculosis

PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Urine analysis for abnormal constituents: protein, fats and glucose. 2. Measuring Erythrocyte Sedimentation Rate (ESR). 3. Tissue processing, embedding and sectioning. 4. Staining and preparation of permanent histological slide. 5. Diagnostic tests for detection of various diseases – CRP, VDRL, RA, Pregnancy, Dengue and HIV (any four) 6. PCR based diagnostics (for any one disease)

SUGGESTED READINGS 1. Robbins and Cotran Pathologic Basis of Disease, 8th edition (2009), Vinay Kumar, Abul. K. Abbas, Jon C. Aster, Nelson Fausto; Saunders Publishers, ISBN-13: 978- 1416031215 2. Robbins Basic Pathology, 9th edition (2012), Kumar, Abbas, Fausto and Mitchell; Saunders Publication, ISBN-13: 978-1437717815 3. General And Systematic Pathology, 2nd edition (1996) J.,Ed. Underwood and J. C. E. Underwood; Churchill Livingstone, ISBN-13: 978-0443052828 4. Textbook of preventive and social medicine, 20th edition, J. E Park; Banarsi Das Bhanot. Publishers. ASIN B0007CBHKI. 5. Medical Laboratory Technology Methods and Interpretations, 6th edition (2009), Ramnik. Sood; Jaypee Brothers Medical Publishers, ISBN-13: 978-8184484496. 6. Pathophysiology, 3rd edition (2012), Lee-Ellen C. Copstead-Kirkhorn and Publisher. Saunders. ISBN-13: 978-1455726509.

BMS-G9: Pharmacology and Toxicology

Preamble: The course provides basic insight into principles of pharmacology and toxicology. It also highlights the pharmacodynamics and pharmacokinetics aspect of drugs in general. The emphasis will be on evaluation of toxicity and mechanism of toxicity of xenobiotics.

THEORY Total Lectures: 48

Unit I: General pharmacology and toxicology (6 Lectures)

Nature and source of drugs, Routes of drug administration and their advantages, Definitions and scope of toxicology. Introduction to ecotoxicology.

Unit II: Mechanism of toxicity (6 Lectures)

Formation of ultimate toxicant of xenobiotics and its interaction with target molecules.

Unit III: Pharmacokinetics (6 Lectures)

Membrane transport, Absorption, Concepts of Bioavailability and half life of the drug, Distribution of xenobiotics. Brief introduction to biotransformation, Phase- I reactions including oxidations, hydrolysis, reductions and phase II conjugation reactions and excretion of drugs.

Unit IV: Pharmacodynamics (6 Lectures)

Mechanism of drug action, Receptors and receptors subtypes, Dose response relationship and combined effect of drugs. Concept of LD50, LC50, TD50 and therapeutic index.

Unit V: Introduction and classification of the drugs acting on:

a. Central and autonomic nervous system, neurotoxic agents. (6 Lectures) b. Cardiovascular system and cardiotoxic agents. (4 Lectures) c. Kidney and nephrotoxic agents. (4 Lectures) d. Drugs/Toxicants acting on Respiratory System (2 Lectures)

Unit VI: Introduction and classification

a. Anti-inflammatory and analgesic drugs and their related toxicity. (4 Lectures) b. Endocrine drugs (2 Lectures) c. Antimicrobial chemotherapeutic drugs (2 Lectures) PRACTICALS (Wherever wet lab experiments are not possible, the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Handling of laboratory animals and various routes of drug administration. 2. To study presence of paracetamol/aspirin in the given sample. 3. Separation of a mixture of benzoic acid, beta- napthol and napthelene by solvent extraction and identification of their functional groups. 4. Determination of Dissolved water (DO) using Winkler‟s method. 5. To determine the total hardness of water by complexometric method Using EDTA. 6. To determine Acid value of the given oil sample. 7. Calculation of LD50 value of an insecticide from the data provided.

SUGGESTED READINGS 1. Essentials of Medical Pharmacology, 7th edition (2010), K.D. Tripathi, Jaypee Brothers, ISBN-13: 978-8184480856. 2. Pharmacology, 7th edition (2011), H.P. Rang, M.M. Dale, J.M. Ritter and P.K. Moore, Churchill Livingstone, ISBN-13: 978-0702045042 3. Cassarett and Doull‟s Toxicology “The Basic Science of The Poisons” 7th edition (2008), Curtis D. Klaassen Editor, McGrawHill Medical. ISBN-13: 978-0071470513. 4. Introduction to Toxicology, 3rd edition (2001), John Timbrell, Taylor and Francis Publishers. ISBN-13: 978-0415247627. 5. Cassarett and Doull‟s “Essentials of Toxicology”, 2nd edition (2010), Klaassen and Whatkins, McGraw Hill Publisher. ISBN-13: 978-0071622400. 6. Principles of Toxicology, 2nd edition (2006), Stine Karen and Thomas M Brown, CRC Press. ISBN-13: 978-0849328565. 7. Lu‟s basic toxicology: Fundamentals target organ and risk assessment, 5th edition (2009), Frank C Lu and Sam kacow, Informa Health care. ISBN: 9781420093117. BMS-G10: Tools and Model Organisms in Biomedical Research

Preamble: This course has been designed to introduce the various tools and techniques in modern era of biology. It focuses on the principles of microscopy, spectroscopy, chromatography, various molecular biology and immunological techniques. This course also aims to give the students an introduction to different model organisms, what they are used for, which techniques that can be applied to modify their genome, and how the students may use these organisms employing modern technological approaches for research and understanding of biology.

It‟s a motley collection of creatures: They fly, swim, wiggle, scurry, or just blow in the wind. But to the scientific community, this compilation has been elevated above all other species. They are the model organisms.-The Scientist, June 2, 2003

THEORY Total Lectures: 48

Unit I: Spectroscopy (5 Lectures)

Principles and biological applications of UV, visible spectroscopy, Fluorescence spectroscopy, Infrared spectroscopy, NMR and Mass spectroscopy.

Unit II: Microscopy (3 Lectures)

Principles of Light microscopy, Phase contrast microscopy, Electron microscopy (EM)- scanning EM, transmission EM and scanning transmission EM (STEM); Fluorescence microscopy.

Unit III: Analytical methods (5 Lectures)

Chromatography: Principle and applications of affinity, gel filtration and ion exchange chromatography, HPLC. Centrifugation: Principle and different types of centrifugation- differential, density gradient and equilibrium. Flow cytometry: Flurochromes, fluorescent probe and principle, application in biomedical science.

Unit IV: Molecular Biology Methods (8 Lectures)

Isolation, purification and quantification of nucleic acids. Agarose gel electrophoresis and PAGE. Hybridization techniques- Southern, Northern and Western. Restriction enzymes, Gene cloning and RFLP. Principles of PCR, RT PCR, Real time PCR. DNA sequencing- Maxam Gilbert and Sanger methods.

Unit V: Immunological methods (3 Lectures)

Monoclonal antibody generation, Isolation of various immune cells and their functional assays, Generation and applications of nude mice. ELISA - direct, indirect, competitive and sandwich ELISA, Co-immuno-precipitation for protein-protein interaction studies.

Unit VI: Introduction to model organisms (2 Lectures)

What are model organisms? Why there is a need to study model organisms? How to choose a model organism?

Unit VII: Different model organisms

The following aspects will be discussed under each model organism listed below. Brief history of model organisms, Life cycle, Culture conditions/maintenance, Advantages and disadvantages of the organism as a model, Fundamental discoveries made so far using these organisms, Discussion on suitability of each for genetic, Developmental biology and as disease models:

Escherichia coli (2 Lectures) Utilization in discovery of fundamental metabolic pathways.

Saccharomyces cerevisiae (Baker’s yeast) (6 Lectures) Mating types and their inheritance. Discovery of cell division cycle genes-cdc mutants,Yeast two hybrid system for protein-protein interactions. Overview of saccharomyces genome database (SGD), Commonly used yeast assays, the 'Yeast Genome Deletion Collection.

Caenorhabditis elegans (Nematode worm) (2 Lectures) Insights into the role of proteases (ced genes) in Coursed cell death, Cell-fate mapping and lineage studies. Discovery of RNAi in C. elegans, Overview of Wormbase database.

Drosophila melanogaster (Fruit fly) (4 Lectures) Insights into forms of cancer and neurodegenerative diseases. Flybase, the Gene disruption project, transgenic flies.

Mus musculus (Mouse) (4 Lectures) “Premier” model organism for studying complex physiological processes. Generation and application of knock out and transgenic mice as disease models. Knockout database.

Introduction to other model organisms (4 Lectures) Dictyostelium discoideum (Social amoeba) as a model for induced multicellularity and differentiation. Danio rerio (Zebra fish) as a model for human disease (any 2).Introduction to tools for Standard mutagenesis and Genetic screening. Daphnia (Water flea) as a model for ecotoxicological studies.

PRACTICALS (Wherever wet lab experiments are not possible the principles and concepts can be demonstrated through any other material or medium including videos/virtual labs etc.)

1. Isolation and spectroscopic quantification of genomic DNA from blood/tissue/ E.coli, determination of melting temperature of DNA. 2. Optimization of PCR conditions for temperature (gradient PCR) and Mg2+ concentration. 3. Restriction digestion of DNA for RFLP and DNA fingerprinting. 4. To perform Southern hybridization. 5. Protein purification by affinity/ion exchange/gel filtration chromatography. 6. To perform sandwich ELISA. 7. Preparation of culture media for Drosophila and study different stages of life cycle of Drosophila. 8. Study of life cycle of Dictyostelium discoideum.

SUGGESTED READINGS 1. Physical Biochemistry: Principles and Applications, 2nd edition (2009), David Sheehan, John Wiley. ISBN-13: 978-0470856031. 2. Cell and Molecular Biology: Concepts and Experiments, 6th edition (2009), Gerald Karp, Wiley. ISBN-978-0470483374. 3. Gene cloning and DNA analysis, 6th edition (2010), T.A. Brown. Wiley-Blackwell ISBN-13: 978-1405181730. 4. Principles of Gene Manipulation and Genomics, 7th edition (2006), S.B. Primrose and R.M. Twyman. Blackwell Scientific ISBN: 978-1405135443. 5. Human Molecular Genetics, 3rd edition (2003), Tom Strachan and Andrew Read; Garland Science Publishers, ISBN -13:978-0815341826. 6. Immunology, 6th edition, (2006), J. Kuby, W.H. Freeman and Company, New York. ISBN-13: 978-1429202114. 7. Genetics: A Conceptual Approach, 4th edition (2010), Benjamin A. Pierce, W. H. Freeman, ISBN-13: 978-1429232524. 8. Molecular Cloning: A Laboratory Manual, 4th edition (2012), Three-volume set by Michael R. Green, Joseph Sambrook; Cold Spring Harbor Laboratory Press, ISBN-13: 978-1936113422. 9. Concepts of Genetics, 10th edition, (2012). William S. Klug, Michael R. Cummings, Charlotte A. Spencer, Michael A. Palladino. ISBN-13: 978-0321724120. 10. Physical Biochemistry: Applications to Biochemistry and Molecular Biology, 2nd edition (1982), David Freifelder, W.H. Freeman and Company. ISBN-13: 978- 0716714446. 11. Principles and Techniques of Biochemistry and Molecular Biology, 7th edition (2010), Wilson K and Walker J., Cambridge University Press, 2010. ISBN-13: 978- 0521516358. 12. Emerging Model Organisms: A Laboratory Manual, Volume 2, Lab manual edition (2010), Cold Spring Harbor Laboratory Press, ISBN-13: 978-0879698652.

ELECTIVE Papers (Choice based papers) for III semester

1. Molecular Oncology 2. Stem cell Biology for developmental and translational research 3. Advance Immunology 4. Medical Virology & Mycology 5. New methods in Organic synthesis

ELECTIVES (Choice based papers) for IV semester

1. Advance Toxicology 2. Genome Biology 3. Neurobiology 4. Pathophysiology 5. Advances in protein science 6. Advance concepts in medicinal chemistry 7. Drug discovery and process development. 8. Bioinformatics, computational biology and drug design 9. Medical Bacteriology and Parasitology

OPEN ELECTIVES To be offered by ACBR Bioethics & Biosafety Application of statistics for Biology

SEMESTER I TOTAL CREDITS/SEMESTER 24

PAPER L T P Credits Biochemistry 3 0 2 5 Concepts of Genetics 3 0 2 5 Biologic chemistry I 3 1 2 6 Cell Biology 3 1 0 4 Medical Microbiology 3 0 1 4

TOTAL 15 2 7 24

SEMESTER II TOTAL CREDITS/SEMESTER 24 PAPER L T P Credits Human Physiology I 4 0 2 6 Recombinant DNA 3 0 2 5 Technology & Biotechnology Immunology 3 1 2 6 Biological Chemistry II 3 1 0 4 Molecular biology 3 0 0 3

TOTAL 16 2 6 24

SEMESTER III TOTAL CREDITS/SEMESTER 24

PAPER L T P Credits Human Physiology II 3 1 0 4 Principles of Medicinal chemistry 4 0 0 4 Pharmacology & Toxicology 4 0 2 6 Techniques & Instrumentation 3 1 2 6 Elective I 4 0 0 4 Or take two open electives Open electives I 2 0 0 2 Open Elective II 2 0 0 2

TOTAL 18 2 4 24

Although they have five papers, they have practicals only on two days so they will get time to do project work or self study.

SEMESTER IV TOTAL CREDITS/SEMESTER 20

PAPER L T P Credits Elective II 4 0 0 4 Elective III 4 0 0 4 Elective IV 4 0 0 4 PROJECT* 8 0 0 8

If a student wish not to do the research project, he/she can take two more electives (electives V and Elective VI).

AT THE END OF TWO YEARS, STUDENT MUST TAKE ATLEAST 92 CREDITS.

HUMAN PHYSIOLOGY-I Core paper II Semester Credits: (3+1) + 2 credit practicals

PREAMBLE:

The goal of physiology is to explain the physical and chemical factors that are responsible for the origin and sustainability of life. Each type of life, from the simple virus to the largest tree or the complicated human being, has its own functional characteristics. Therefore, the vast field of physiology can be divided into many divisions. In human physiology-I course, we attempt to explain the various features and mechanisms of the human body that make it a living being. The very fact that we remain alive is almost beyond our control, for hunger makes us seek food and fear makes us seek refuge. Sensations of cold make us look for warmth. Thus, the human being is actually an automaton, and the fact that we are sensing, feeling, and knowledgeable beings is a part of this automatic sequence of life and these attributes of our being living propel us to understand the various biological phenomenon and its alteration in the diseased state. This course starts with the basic understanding of being living from the cell itself and in the process, course through various organ systems and their functioning.

UNIT 1: Membrane and muscle physiology: cell membranes are ubiquitous from cell organelle to organ system so its imperative to understand the basic structure and function of membranes and how they can modulate the function of an organ system as whole starting with the emphasis on the nerve and skeletal muscle cell. L1: Organization and functional systems of the cell with reference to nerve and muscle cells: Fluid mosaic model of the membrane, Fluidity, Transport of ions and molecules through cell membrane: diffusion and active transport. L2: Concept of Membrane potentials: types of membrane potential, resting membrane potential, graded and action potentials, methods to record and observe membrane potential. L3-6: Physiologic anatomy of skeletal muscle, neuromuscular transmission and excitation- contraction coupling, Molecular mechanisms of muscle contraction, Energetics of muscle contraction, muscle fatigue, motor unit recruitment, size principle, muscle mechanics, and Electromyogram.

Tutorial: Group discussion, Student seminar and test

UNIT 2: Respiratory system L7-8: Anatomy and Functions of respiratory passageways, pulmonary circulation, pulmonary edema and pleural fluid. L8-9: Pulmonary ventilation: mechanisms of pulmonary ventilation, pulmonary volumes and capacities, alveolar ventilation. L10-11: Physical principles of gas exchange, Diffusion of gases through respiratory membrane, Transport of oxygen and carbon dioxide in blood and body fluids. L12: Regulation of respiration: respiratory center, peripheral chemoreceptor system, central chemoreceptor system and their regulatory function. L13-14: Respiratory Adjustments in Health & Disease: Effects of Exercise, Other Forms of Hypoxia, Oxygen Treatment, Hypercapnia & Hypocapnia, Effects of Increased Barometric Pressure, Artificial Respiration, Respiratory acidosis and alkalosis, Regulation of acid-base balance.

Tutorial: Group discussion, Student seminar and test

UNIT 3: Body fluid and excretory system L15: Body fluid compartments: Basic principles of osmosis and osmotic pressure: Extracellular and intracellular fluids, Interstitial fluid and edema with its etiology. L16-18: Urine formation by kidneys: renal blood flow and their control, Glomerular filtration, Determinants of glomerular filtration rate, Tubular processing of glomerular filtrate, Reabsorption and secretion along different parts of nephron, L19-21: Regulation of tubular reabsorption, Functions of kidneys in homeostasis, Diuretics, Micturition and disorders of Non-excretory function of kidney L22: Integration of renal mechanisms for control of blood volume and extracellular fluid volume. L23-24: Regulation of extracellular fluid osmolarity and sodium concentration, Role of thirst in controlling extracellular fluid osmolarity and sodium concentration, Renal regulation of potassium, calcium, phosphate and magnesium.

Tutorial: Group discussion, Student seminar and test

UNIT 4: Gastrointestinal system L25-26: Histology of Gut with Characteristic features and functioning of smooth muscle lining the gastrointestinal tract. L27-28: General principles of gastrointestinal function - motility, nervous control, and blood circulation, Transport and mixing of food in the entire alimentary tract, sphincters of gastrointestinal tract. L29: Ingestion of food, vomiting, motor functions of stomach, Defecation and its control. L30-32:Secretary functions of alimentary tract: Secretion of saliva, Gastric secretion, pancreatic secretion, Secretion of bile by liver, Secretions of small and large intestine. L33-34: Digestion and absorption in gastrointestinal tract, Digestion of various foods, Neuronal regulation of feeding, obesity and starvation.

Tutorial: Group discussion, Student seminar and test

UNIT 5: Reproductive system Anatomical and functional aspects of human genital system L35-36: Sex Differentiation & Development, Aberrant Sexual Differentiation, Embryology of the Human Reproductive System, defects of reproductive system, Puberty: Precocious & Delayed Puberty, Menopause L37-38: Male: Gametogenesis, Development structure and function of testis with Ejaculation, Control of Testicular Function, Abnormalities of Testicular Function, L39-40: Female: Gametogenesis Development structure and function of ovary The Menstrual Cycle, Control of Ovarian Function, Abnormalities of Ovarian Function L41-42: Pregnancy: conception, fetal development, placenta, parturition, Lactation, fertility and infertility, Physiological concepts for a planned family

Tutorial: Group discussion, Student seminar and test

UNIT 6: Endocrine system L43-44: Anatomy and structure, formation, secretion and regulation of hormones, hypo- and hyper secretions. L45-46: Diseases of the following glands Thyroid, Adrenal, Parathyroid, Pituitary Thyroid Anatomic Considerations, Formation & Secretion of Thyroid Hormones, Transport of Thyroid Hormones, Effects of Thyroid Hormones, Regulation of Thyroid Secretion, Clinical Correlates. L47-48: Adrenal Medulla, Structure & Function of Medullary Hormones: Regulation of Adrenal Medullary Secretion, Adrenal Cortex Structure & Biosynthesis of Adrenocortical Hormones L49-50: Effects of Adrenal Androgens & Estrogens, Physiologic, Pharmacologic & Pathologic considerations L51-52: Effects of Glucocorticoids, Regulation of Glucocorticoid Secretion, L53-54: Effects of Mineralocorticoids, Regulation of Aldosterone Secretion, Summary of the effects of Adrenocortical Hyper & Hypofunction in Humans. L55-56: The Parathyroid Glands, Calcitonin, Effects of Other Hormones & Humoral Agents on Calcium Metabolism, Posterior pituitary hormones Growth Hormone

Tutorial: Group discussion, Student seminar and test

COURSE OUTCOME Human physiology I: This course is a part of core course offered in second semester. On satisfying the requirements of this course, students will have the knowledge and skills to: 1. Describe the anatomy and histology of major organ systems. 2. Explain the functioning of these organ system in maintenance of normal and healthy individuals 3. Narrate the contribution of each organ system to the maintenance of homeostasis. 4. Interpret and analyze the human physiological data, and responses to experimental conditions 5. Understand the physiological processes accurately with relevant scientific terminology and nomenclature leading to develop more consciousness towards a healthy body. 6. List the physiological principles underlying pathogenesis and treatment of disease.

Reading list:

1. Textbook of medical physiology by Arthur C. Guyton and John E. Hall; Ed.13th & 14th. 2. Review of medical physiology by William F. Ganong; Ed. 23nd; McGraw Hill; 2010. 3. Essential medical physiology by Leonard R. Johnson and Ed. 3rd; ELSEVIER; 2003. 4. Principles of anatomy and physiology by Gerard J. Tortora and Bryan Derrickson; Ed.15th; John Wiley; 2016. 5. Hole's Human Anatomy & Physiology, McGraw-Hill Education; 14th edition, 2015 6. Medical Physiology: A cellular and molecular approach by Walter F. Boron and Emile L. Boulpaep; Saunders; Ed. 3rd, 2017. 7. Physiology by Robert M. Berne and Matthew N. Levy; Mosby; ELSEVIER, Ed.7th 2018. 8. Essentials of Anatomy & Physiology Plus Mastering A&P with Pearson (7th Edition) 2016

HUMAN PHYSIOLOGY PRACTICALS II Semester Credits: 2

Detailed practicals

Histopathology 1. Demonstration of biological sample retrieval, sectioning (cryotome/microtome), fixation and staining of various tissue types from rodent tissue sample. 2. Study of various types of human tissues in normal and diseased condition from permanent slides.

Blood physiology 1. Preparation and staining of blood smear with Leishman’s stain and Identification of the various types of blood cells. 2. To record the Bleeding time, clotting time and determine the blood group from own blood sample. 3. To determine the total count of RBC and WBC from own blood sample.

Electrophysiology (using appropriate hardware and software) 1. To observe, record, and correlate motor unit recruitment and muscle fatigue with increased power of skeletal muscle contraction through Electromyogram (EMG). 2. Measurement of forced expiratory volume (FEV) and Forced vital capacity (FVC). 3. To observe rate and rhythm changes in the ECG associated with body position and estimate the mean electrical axis of the QRS complex 4. To measure reflex time of different nerves in the body under different conditions using the reflex hammer. 5. To record the Reaction time for various Short term memory test. 6. To record an EEG of different areas of brain from an awake, resting subject. 7. Record EOG on the horizontal plane and compare eye movements under the following conditions: pendulum tracking, pendulum simulation, reading silently, reading aloud, and reading challenging material or material written in an unfamiliar language. 8. Assessment of cranial nerves functioning by the battery of non-invasive tests.

Reading list

1. Exploring Anatomy & Physiology in the Laboratory, Morton Publishing Company; 3 edition (2017) 2. http://physiology.elte.hu/gyakorlat/jegyzet/Physiology_Pactical_(2013).pdf

Semester II: Recombinant DNA technology and Biotechnology

CORE Subject (Credit 3+2(p))

Preamble: The unique preposition of this subject paper is that the students learn the advancement in basic molecular techniques and different methodologies used in the diagnosis and for the various human diseases therapeutics. The concepts of gena cloning and its expression leading to desired gene product is explored. Aims in the paper is to train students towards the advancement

Total 50 Lectures

L (1-5): Prokaryotic Restriction Modification system, Types of Restriction endonucleases & restriction maps, Endonucleases produces 3’ Overhang and 5’ Overhang, Producing new restriction endonuclease sites.

L(6-9): Various RDT enzymes such as S1 nuclease, Alkaline phosphatases, polynucleotide kinase, mung bean nuclease their mechanism and application

L(10-13): Vectors-Origin of cloning vectors and various modified versions of vectors, Bacterial, yeast expression vectors, mammalian expression vector

L14: Tutorial Class

L(15-18): Cloning vectors, Tetracycline regulated vectors, shuttle vectors, YAC &BAC.

L(19-22): Principles of selection of gene cloning, preparation of probes, Blue white selection, insertional inactivation, LacZ application, luciferase reporter system

L(23-25): Detection and identification of cloned DNA sequencing, methods of DNA sequencing, pyrosequencing, nanopore sequencing, Next generation sequencing

L(26-30): Application and principles of Polymerase Chain Reaction, RFLP analysis, real time PCR, Disease diagnostics eg: genetic diseases (cystic fibrosis, sickle cell anemia, hemophilia etc), detection of pathogenic strain, single nucleotide polymorphism in disease diagnosis

L31: Tutorial Class

L(32-35): Gene Mutagenesis-Different methods used to generate recombinant mutants (deletion and point mutations), exonucleases, S1 nuclease, Genome editing system using ZFN, CRISPR, TALEN

L(36-37): Application of recombinant DNA technology, DNA fingerprinting in forensic sciences

L(38-41): Biotechnology towards therapeutics, Gene therapy (Viral on non-Viral), Adenoviral vectors or retroviral based gene therapy, stem cell based disease diagnosis and therapies

L42: Tutorial Class L(43-45): Introduction to the concept of Regenerative Medicine, Advance Pleuripotent stem cell derived therapies, Induced pleuripotent stem cell, mesenchymal stem cell

L(46-48): Exosomes: Biomarkers, Cancer diagnosis, Tissue repair

L(49-50): Bio-safety and ethics for recombinant DNA technology

L51: Tutorial Class

Text Books:

a) Principles of Gene manipulation (Primrose), 7th Edition b) Molecular Cloning (A laboratory manual), Vol 1, Vol 2, Vol 3 c) Molecular Cell Biology (Lodish), 7th Edition d) Review articles from: Nature Reviews (Journals)

Recombinant DNA technology and Biotechnology Practicals:

1) Primer designing for gene amplification using PCR, and other types of primers for real time PCR based detection or analysis 2) Preparation of Various solutions and Buffers, cell culture LB (Luria-Bertani) media preparation, LB-Agar Plates, Ampicillin Antibiotics preparation, autoclaving, sterilized surface, laminar flow operation. 3) Adopting calcium chloride methodology for Competent cells preparation 4) Polymerase Chain Reaction based gene amplification and recombinant formation using cloning vector 5) Recombinant plasmid isolation and preparation 6) Recombinant restriction digestion of DNA and excision of DNA from Agarose gel 7) Heat shock methodology based recombinant transformation, competent efficiency calculation and Blue white colony screening 8) Application of Polymerase Chain Reaction based infectious or non-infectious disease diagnosis 9) Loop mediated isothermal amplification assay 10) Concept of cell culture (Demonstration)

Subject Outcome:

Theory & Practical Outcome:

1) M.Sc. student after attaining recombinant DNA technology course work, they are then well versed with the knowledge and practical approach to pick out any gene from cell or tissues using some potential technique using PCR technology, where student can amplify the interested gene, and to clone in any expression vector to produce more protein, for functional studies. 2) Cloning any gene of interest can help students to analyze the isolated gene and complete sequencing, will help in disease manifestation. 3) Applications of subject knowledge has commercial values 4) Developing a diagnosis technique for the disease treatment, at low cost values 5) Developing a efficient therapies against various diseases to work IMMUNOLOGY

Core paper

II Semester

Credits: 4+0+2 (practical)

56 lectures

Preamble: Immunology course has been formulated to understand the basics of vertebrate Immune system at the molecular, cellular and organ system level and to know how our body defends to the “Danger/ foreign” entities . The students will understand primary and secondary lymphoid system in mouse and human system . The practical and theoretical illustration of functions of cells of innate immune responses: macrophages dendritic cells through estimation of reactive oxygen species, reactive nitrogen species, malondialdehyde, protein- carbonyl adducts, process of phagocytosis and activation of immune cells etc. Understand the mechanisms of cell mediated and humoral immune responses at organ system , cellular and molecular level.

L1: History and scope of Immunology

L2: Introduction to Immune System , concepts of Innate and acquired Immune responses , Active and passive Immunity , Natural and artificial immunity, primary and secondary immune responses

L3: Lymphoid System- overview . Lymphatic system and lymphocyte traffic .Lymphoid Tissue: Primary and Secondary Lymphoid organs. Anatomy and functional significance of Thymus, Bone marrow

L4: Anatomy and functional significance of spleen ,various lymph nodes, MALT,GALT, NALT,ILT

L5: Cells involved in the Immune Response : Structural and functional features of cells involved in immune responses and their relative significance. Lymphocytes (B& T lymphocytes), NK Cells

L6: Mononuclear Phagocytes, Antigen- presenting cells, Polymorphonuclear cells, eosinophils, basophils and mast cells, Cluster designation Ag specific receptors (comparison of Human and Mouse Lineages)

L7 is Tutorial

1 L8: What is an immune response. Evolution of cells and molecules of the immune system with associated functions. Dendritic cells: discovery types and functions: DC 1 vs DC2 vs Follicular DC.

L9: Antigen recognition processing, presentation and cross-presentation of antigens by DC subsets

L10: DC priming of T independent antigens, DCs as immunotherapeutics

L11: Innate immune system: overview. Cells and receptors of the innate immune system. Diversity in Antigen recognition receptors of innate immunity

L12: Signaling from Toll Like Receptors

L13: Cell surface and intracellular antigen/pathogen recognition systems: NOD/NLR/TLR9

L14: Secretory receptors of innate immune system and their functions

L15: Innate memory and danger hypothesis. Macrophages: types, location and function. Neutrophils and NK cells: mode of action and neutralization of pathogens

L16 is Tutorial/Test

L17: Antibody Generation, structure and Function : Over View of Humoral immunity, Clonal Selection Theory, Immnoglobulins classes and their functions , Antibody Structure and Function

L18-19 : Antibody Effector Mechanisms, Antibody Receptors, Basis of Antibody Diversity, Mechanisms of Immunogolubin Gene Recombination, and B cell development

L20: Mechanism and Effect of Somatic Mutations on the Antibody Diversity, Mechanism of Ab Class switching.

L21 : Antibody Responses in vivo, Enhanced Secondary Responses , significance Isotype switching, Affinity Maturation and development of Memory responses.

L22-23 : Major Histocompatibility Complex overview and significance. Structure of MHC Class I Molecules, Structure of MHC Class II Molecules,

L24: Genomic Organisation of the MHC locus in Mice and Humans, Diversity of MHC molecules and their effect of immune response modulation.

L25 : Gene polymorphism and polygeny on MHC locus and their effect on the disease pattern with respect to resistance and susceptibility to diseases.

2 L26-27 : Antigen Recognition and Presentation overview: Structure and assembly of MHC molecules/Peptide complexes. Mechanisms of Antigen Processing (exogenous and endogenous antigens) and Presentation to T-lymphocytes (CD4+ and CD8+).

L28-29: Complement System. Nomenclature of complement system, Classical, Lectin and Alternative Activation of complement pathway, assays for complement activation. Biological Effects of complement system , Regulation of complement system. Complement system related diseases

L30 is Tutorial

L31-33 : Cell Mediated Immune Response Overview, T lymphocyte classification, lineage and Mechanisms of development of T cells in thymus. Structure of T cell receptors , Mechanisms of recombination and diversity of TCR genes, self tolerance mechanisms. Regulation of innate and humoral responses by T cells. T cell APC interactions and modulation of Immune responses.

L 34 : T independent and T dependent Defense Mechanisms, Cell Mediated Cytotoxicity. Idiotypic modulation of immune responses

L35-36 : Regulation of Immune Response: Antigens, classification of antigens based on their interaction and functions. Superantigens, interaction of Antigens with Antigen Presenting Cells, Antibody, Lymphocytes. Idiotypic Modulation of Response, Neuroendocrine Modulation of Responses, Genetic control of Immune Response.

L37 : Cell Migration and Adhesion. Patterns of Cell Migration, Structure and function of various adhesion Molecules, Mechanism of Cell Migration and their involvement in disease

L38-39 : Immunopathology: overview Rh- blood groupings, Autoimmune Diseases, Basis of breach of central and peripheral tolerance.

L 40 : Immuno-deficiencies, Genetic disorders congenital and acquired.

L 41-42 : Hypersensitivity Reactions (type I and type IV), Role of 1gE, Mast cells, Genetic basis of Allergic Response and pathogenesis.

L 43 : Immune Tolerance overview: Self Tolerance, Transplantation and Rejection mechanisms

L44 is Tutorial

L 45-46 : Mechanism of Antigen-Antibody Interaction, Experiment based evidence to calculate antigen binding sites, avidity, affinity. Immunological Techniques: Principles, significance and methods; Agglutination( Direct/Indirect), Precipitation(Radial and double immunodiffusion) and Radioimmunoassays.

L 47 : Immunological techniques : Immunoflorescence ( direct/ indirect) , Enzyme linked Immunosorbent assay ( principles of various types of ELISA) and its variants.

L48 : Magnetic cell sorting, Flowcytometry, western blotting

L49 : Techniques for generation of polyclonal and monoclonal antibodies. Hybridoma Technology for Mab Production.

L 50 : Techniques for isolation of specific antibodies.

L 51 : Gene Targeting: Knock out and Transgenic animals

L 52 : Basis of Tumor Immunology

L 53 : Vaccines : History and overview , adjuvants, Immune responses following vaccination

L 54 : Various types of vaccines and methods of their development with examples

L 55 is Tutorial

L 56 is Test

Course outcome Immunology is one of the foundation courses for the biomedical sciences students. Students will gain insights on the immune system and the immune responses at the molecular , cellular and organ system level. The students will be prepared to take further advanced courses/ research in immunology , immunodiagnostics , immunopathogenesis and immunotherapeutics .

Suggested Readings

1. Fundamental Immunology William Paul (Ed) 2017. Lippincott Williams & Wilkins.

2. Kuby Immunology by Thomas Kindt and Richard A. Goldsby and Barbara A. th Osborne; Ed. 6 edition. W.H. Freeman and Company, New York; 2007

3. Cellular and molecular immunology by Abul K. Abbas and Andrew H. th Lichtman and Shiv Pillai; Ed. 6 ; Saunders, 2007.

th 4. Immunology; Ed.7 by David Male and Jonathan Brastoff and David B. Both and Ivan Roitt; Mosby Elsevier; 2006.

4 5. Immunobiology: the immune system in health and disease by Charles A. th Janeway and Paul Travers and Mark Walport and Mark J. Shlomchik; 7 Ed; Garland Science; 2008.

6. Immunology of infection diseases by Stefan H. E. Kaufmann and Alan Sher and Rafi Ahmed; ASM Press, Washington; 2002.

7. Essentials of immunology & serology by Jacqueline H. Stanley; DELMAR; Australia; 2002.

Practicals:

1-3. To demonstrate that activation of peritoneal macrophages/ myeloid lineage cells by lipopolysaccharides results in reactive oxygen production (RNS) and reactive nitrogen species production. Estimation will be done by flowcytometry, Colorimetry and microscopy assays. 3-6. The antigen antibody interaction mechanisms will be demonstrated by precipitation and agglutination assays (octerlony, mancini methods and indirect agglutination tests) 6-9. The T cell and B cell separation and their proliferation will be done using MACS and FACS

10. Proinflammatory cytokine expression will be demonstrated in activated cells by ELISA or immunofluorescence.

5 NAME OF PAPER : BIOLOGICAL CHEMISTRY 2 CORE PAPER ; Semester II, Credits 4

Preamble

The course aims to impart to the students a thorough understanding of chemical macromolecules found in biological systems. Synthetic macromolecules and their self assembly is also discussed as is the important area of nanotechnology. Carbohydrate chemistry forms an essential part of this course. Enzyme and coenzyme catalysis is thoroughly discussed

Molecules and macromolecules in biological systems

L-1 Amino acids, peptides and proteins, L-2 Structure and Functions of proteins L-3 Formation of peptide bonds, L-4-5 Protecting groups and peptide bond formation, L-6-7 protein degradation and sequencing of amino acids, L-8 DNA and RNA bases, L-9-10 nucleosides and nucleotides, phosphodiesters L-11-12 formation of N- and C- glycosides, L-13-14 conformation and configuration of 5 carbon and 6-carbon sugars, L-15-16 maltose, sucrose and lactose,

Synthetic macromolecules and polymers in biology

L-17-18 Building of macromolecules and molecular frameworks and their biomedical applications. L-19 Synthetic strategies for artificial systems that mimic biological entities, L-20-23 applications of supramolecular principles to molecular diagnosis, therapeutic applications of supramolecular chemistry. L24-26 Nanotechnology and its applications in drug delivery and other biomedical applications

Mechanisms in Biological Chemistry

L-27 Active methylene groups, L-28-29 aldol and retroaldol reactions, L-30 schiff bases and enamine reactions, L31-32 nitrogen, phosphorus and sulfur ylides. L-33 Umpolung reaction, L-34 Michael addition, L-35 Polymer supported organic reactions, L-36 -37 phase transfer catalysis, Equivalence of these reactions in biological system Enzyme and Coenzyme systems

L-38 Enzyme classifications, Inhibitors, L-39-40 Mechanisms of Enzymes.

Mechanism of coenzyme catalysis,

L-41 Coenzyme A, L-42 NAD+ and NADPH, L-43 FMN and FAD, L-44 biotin , L-45 PLP, L-46 TPP, L-47 lipoic acid, tetrahydrofolate, ascorbic acid, L-48 cyanocobalamine and L-49 cytochrome P-450

Hammett and Taft equation

L-50 Steric and solvent effects, L-51 role of pH, L-52 role of reaction media on certain reactions

MBS 202: MOLECULAR BIOLOGY (CORE PAPER)

Credits :3 (3+0+0)

Preamble: Molecular Biology is a core course where in students will be explained the various basic processes of the prokaryotic and eukaryotic cell. Several essential techniques used in understanding its gene expression, DNA synthesis and translation will also be discussed.

TRANSCRIPTION IN PROKARYOTES & EUKARYOTES L1: Basic concepts of transcription in prokaryotes using E-coli as an example L2: Structure & function of RNA polymerases. L3: Transcription initiation, proteins involved in initiation, L4: Experimental evidence to check their function. L5: Transcription elongation and termination. L6: TUTORIAL L7: Transcription in eukaryotes- differences and similarities, inhibitors of transcription L8 : Structure of TFIID, and other general transcription factors. L9: Methods to identify the subunits of complexes. L10: Post transcriptional regulation of transcription (polyadenylation, capping), mechanism and their role in transcription L11: Transcription regulation by methylation, acetylation of histones.

L12: TUTORIAL L13: Inhibitors of transcription in prokaryotes and eukaryotes L14: Determining the mRNA half life of mRNA. L15: Promoter structure and Transcription by RNA polymerase I, L16: Structure of Promoter and Transcription by RNA polymerase III L17: TUTORIAL L18: TEST (10 MARKS) Regulation of gene expression in Prokaryotes

L19: Coordinated control of clustered genes-operon model, with example of inducible systems like Lac– Operon.

L20: Experimental proof for the operon, use of mutants of I gene, Oc mutants in understanding operon function

L21: Role of cyclic AMP, catabolite repression and regulation by glucose.

L22: Repressible systems like Trp operon. Concept of attenuation L23: Trp operon condt. L24: Arabinose operon concepts of dual role of regulatory protein L25: Arabinose operon contd L26: Identification and understanding the role of sRNA in gene regulation in prokaryotes. L27: Other regulatory pathways in prokaryotes L28Tutorial L29: Test

Regulation of Gene expression in Eukaryotes

L30: Introduction-Organization of genes in eukaryotic DNA Repetitive DNA sequences, multiple regulatory sequences, activators, coactivators, repressors

L31: Activators contd, enhancers. Modular structure of transactivators (Zn fingers, HLH, HTH etc).

L32: Repressor complexes, mechanism of their function in gene regulation.

L33: Regulation of gene expression by hormone receptors. Concept of half-site. L34: Methods used to study protein-DNA interactions EMSA controls, supershift etc. L35: DNA foot printing, reporter assays to prove binding.

L36: TUTORIAL

L37: Homodimers and heterodimers in differential gene regulation with examples. Diseases linked with altered gene expression

L38: Methods used to study protein-protein interactions (i) yeast two hybrid, controls, library screening to identify new interacting partners.

L39: (ii) Concept of co-Immunoprecipitation, uses, advantages and disadvantages of two techniques L40: Alternate splicing in gene regulation, mechanism. L41: Alternate splicing contd. splicing factors etc, gene editing L42: Ribozymes–Structure and mechanism of action. L 43: microRNA and its role in gene regulation (in brief). L44: TEST (MARKS 10)

Chromatin remodeling

L45: Introduction to chromatin remodeling concepts and factors involved. Role of various remodeling proteins such as NURF, ACF

L46: Role of DNA and histone methylation and histone acetylation in chromatin remodeling and gene regulation.

L 47: Concept of insulators, nuclear matrix in gene regulation

L48: Methods to understand chromatin remodeling.

Course outcome: Student should be able to understand the differences and similarities in prokaryotic and eukaryotic gene expression and its regulation. Student will be able to analyze the data on protein DNA interaction. He/She should be able to design experiments for testing whether a new protein is a transactivator and how to identify the binding site on a promoter.

BIOCHEMISTRY Core paper Ist Semester Credits: (3 + 0 + 2 = 5)

Preamble Understanding about protein structure, function and their relations has been key toward understanding almost all biological processes as proteins and enzymes are machineries in the cells. Moreover, contemporary biochemistry needs the thorough understanding of the basic processes like transcription, translation and replication and how different protein complexes and domains interact to perform these processes.

Protein Structure

L1-L2. Protein folding, Secondary and tertiary structure of protein: a helix, ß sheets, examples of proteins, Ramachandran plot

L3. Factors effecting secondary and tertiary structure (disulphide bonds, heat, organic solvents, detergents).

L4. Concept of Motiff and examples of some common structural motifs in proteins.

L5-L6. Domains, structural diversity of different domains with appropriate examples, domain swapping with examples, Protein Dynamics: concept of macro states & ensembles, how dynamics affects protein function

L7. Intrinsically disordered proteins, structure and function of alpha, beta and kappa casein, functional and evolutionary significances, role in different multi-protein complexes

L8. Structure and function of hemoglobin: conformational studies, binding of oxygen and it's release, oxygen saturation curves.

L9. Structural proteins: structure of collagen, keratin and other fibrous proteins.

L10. Disorder of amino acid and protein metabolism.

Tutorial & Class Test

Enzymology

L11. Introduction: General characteristics of enzymes, definition of coenzyme, holo- enzyme, prosthetic groups, classification.

L12-L14. Enzyme Kinetics: Substrate, active site, transition state, activation energy, equilibrium constant Km, Vmax, specificity, Michaelis-Menten equation.

1 L15. Reaction Mechanism: Acid-base catalysis and covalent catalysis (giving examples).

L16-L17. Regulation of enzyme activity: Reversible and irreversible inhibition (non- competitive, uncompetitive) and their effects on Km and Vmax, effect of pH, heat, PMSF and other inhibitors.

L18. Models to explain their kinetic behavior. Problems on enzyme kinetics:

L19. Determination of active sites and turnover number, factors affecting enzyme functions

L20. Bi- substrate enzyme kinetics: ping-pong and sequential mechanism

Tutorial & Class Test

Protein purification, physical separation & Analysis L21. Methods of protein production, isolation, purification strategies, concept of inclusion body

L22. Chromatography (ion exchange, affinity, size exclusion),

L23. Dialysis, molecular sieving, PAGE, electrofocussing, FPLC

L24. Methods of protein sequencing: N and C-terminal analysis, Edman degradation

Regulation of protein function L25. Concept of Structural allostery, examples of self-inhibited proteins, limited proteolysis,

L26-L27. Post-translational modifications: enzymatic and non-enzymatic,

L28. Protein quality control system: ubiquitination, proteosomal and lysosomal- mediated degradation,

L29. Molecular chaperones (structure and functional mechanisms of Hsp90, Hsp70, Hsp60 & Hsp40)

L30. Chaperonin (structure of GroEL & GroES).

Tutorial & Class Test

DNA REPLICATION IN PROKARYOTES AND EUKARYOTES

L31: Concept of origin of replication, experimental evidence for bidirectional and semiconservative replication

L32: Mechanism of DNA Replication: Structure and function of DNA polymerases. Experimental approach to differentiate and identify replication proteins

L33: Role of helicase, primase, gyrase, topoisomerase and other proteins in DNA replication in E.coli.

L34: Replication mechanism in viruses, mitochondrial DNA replication (D loop)

Tutorial & Class Test

L35: Replication in eukaryotes, differences from prokaryotes, experiments to prove the model of replication.

L36: Initiation of replication, proteins involved, their functions, Inhibitors of replication

L37: Elongation and termination of DNA synthesis in prokaryotes and eukaryotes.,

L38-39: Replication at telomeres, Diseases associated with defective DNA replication.

Tutorial & Class Test

Translation L40: Translation in Prokaryotes-initiation:

L41: activation of amino acid, role of 30s and 50s ribosomal subunits

L42: role of 30s and 50s ribosomal subunits, initiation factors

L43-44: Shine-dalgarno sequences, Kozak sequences, selection of first AUG in eukaryotic mRNA with experimental evidence.

L45: Elongation factors, peptidyl transferase termination signal, release factors.

L46-47: Inhibition of protein synthesis - by antibiotics and inhibitors of eukaryotic translation

L48: Methods to determine Half-life of protein.

Tutorial & Class Test

Practicals 1. Preparation of buffers and other solutions 2. Salting in and salting out of proteins. 3. Void Volume estimation 4. Desalting of proteins by dialysis 5. Desalting of proteins by Sephadex G-25 6. Protein estimation by Lowrys & Bradford methods. 7. Protein estimation by Lamberts & beer law 8. Ion-exchange chromatography.

3 9. Affinity chromatography for protein: (i) protein induction & binding to affinity column (ii) running gel & analysis 10. To check purity of protein & subunit structure by SDS page silver staining (i) reducing Gel (ii) non reducing Gel 11. (i) Running Western blot of a specific protein: (i) SDS, transfer & blocking and (ii) probing with antibodies & analysis of result 12. To run Native Gel of a protein/Far western blot. 13. Protein & Nucleic Acid blasts, Clustal W and sequence alignment etc. 14. Measurement of Enzyme activity parameters 15. Measurement of Enzyme inhibition mechanisms

Suggested Readings 1. Proteins: Structure and Function; David Whitford; 1st Ed; Wiley, 2005. 2. Biochemistry by Donald Voet and Judith G. Voet; Ed. 4th ; Wiley; 2010. 3. Lehninger principles of biochemistry by David L. Nelson and Michael M. Cox; Ed. 6th ; W.H. Freeman, 2012. 4. Biochemistry by Christopher K. Mathews and Kensal E. van Holde and Kevin G. Ahern; Ed. 3rd ; Prentice Hall, 1999. 5. Biochemistry by Jeremy M. Berg and John L. Tymoczko and Lubert-Stryer; Ed. 6th ; W.H. Freeman, 2008. 6. Fundamentals of Protein structure and function, Buxbaum Engelberg; Springer, 2015.

Course Outcome Students will be able to have a comprehensive understanding of the diversities of protein structure, mechanisms how enzymes work and also the structure function relation. Students will also develop ideas of how important the fidelity of protein folding in the cells and its connectivity to the development of human diseases. The basic concepts of the protein biosynthesis, DNA replication and transcription are revised. The students are taught the various experimental techniques which led to the development of these concepts. This initiates the analytical and experimental approach of solving any problem.

Practical part of the paper will help to develop skills on protein purification, analysis, quantitation and checking purity by various techniques.

4 Revised Syllabus: ACBR CBCS April 2018

M.Sc. Biomedical Sciences MBS-105 Concepts in Genetics Core Course Credits 3 +2 Practicals Sub-committee: Dr. Richa Arya, Dr. Ankita Narang, Prof. Vani Brahmachari. Feedback from: Dr. Gautam Kshatriya.

Preamble: This course would be offered as compulsory course in the second semester for M.Sc.- Ph.D. combined course in Biomedical Sciences. Most of the undergraduate courses have introduction to Mendelian Genetics as a topic under their syllabus. But it is necessary in our experience to refurbish this in the context of the molecular biology that has changed the implication and meaning of genetic terminologies. Though Mendel’s work had a strong mathematical basis and hence analytical, genetics often has the negative reputation of being loaded with terminology. But the interface of molecular biology with genetics has changed this scenario thus making it even more logical. This course is meant to highlight the basis of inheritance, the deviations from Mendelian genetics and reflect the immense contribution of model systems to understand the genetic basis of biological processes /systems.

Course outcome: At the end of the course the students are expected to recognise the insight of Mendel, and his successors, T.H.Morgan and his illustrious academic lineage, the intuition of Barabara McLintock and the amazing superimposition of epigenetics over genetics. They should be able to understand how the ratio of segregation and patterns of inheritance reflect the underlying molecular logic and why it is unreasonable to expect a purely Mendelian pattern of inheritance in any system given the molecular basis. The introduction to development as route to cellular asymmetry in prokaryotes and yeast mating type.

1. The students will be able to understand genetic interaction in terms of molecular basis. 2. They will know the genetic basis of several chromosomal anomalies and syndromes. 3. The nature of novel mutational processes. 4. They will get an idea of mapping genes using model organisms like, Drosophila, yeast and Neurospora. 5. The original experiments that led to the concepts of mutation occurrence and genetic analysis of bacteria and their virus. 6. They will know the current concepts of epigenetics, dynamic mutations and sex determination in humans and Drosophila. 7. They will be introduced to network and novel molecular processes in the regulation of gene function in Yeast mating type switching and the phage lamda; as an evolutionarily maintained theme of differential expression and its cascading effect on functional specialization during development.

Revised Syllabus: ACBR CBCS April 2018

Section A;

L1-4: Introduction to the Science of Genetics: Genetic terminology Impact of Genetics on other disciplines. Mendelian Genetics: Mendelian Laws of inheritance, its application in animal Genetics, analysis of results of Genetic crosses by various methods.

L5-7: Chromosomal basis of inheritance and data analysis: Sex chromosomes in grasshopper, Development of the concept of co-linearity of genes on chromosomes, Non-disjunction in Drosophila and its role in deciphering chromosomal basis of inheritance. Analysis of patterns of inheritance, Punnett square, statistical methods.

L 8 & 9: Deviations from Mendelian Genetics I: Codominance, incomplete dominance, RFLP markers, gene interactions, multiple alleles, Understanding possible Molecular basis/biochemical basis of gene-interaction.

L 10- 13 : Mutation and mutational analysis: Spontaneous occurrence of mutations in bacteria Lederberg and Lederberg experiment, Types of mutations i.e. point mutations, deletions, rearrangements, insertions, dynamic mutations (repeat expansions) with appropriate examples, Chromosomal anomalies and related syndromes.

L 14 &15: Mutation mapping using balancers, Clb technique in Drosophila.

L16 &17: Linkage as a deviation from Mendelian Genetics: Recombination, Gene mapping using Drosophila as an example, experiments demonstrating physical basis of recombination, crossing over. Gene mapping using special systems, yeast and Neurospora.

L18 &19: Bacterial and Phage genetics: Transformation, transduction , Conjugation, genetic map construction in E.coli. Phage genetics, fine structure of rII region, work of Seymour Benzer., highlighting the design of experiment and choice of the experimental model.

L20 & 21: Genetic Variation; transposition and its application in genetic studies. Extra chromosomal inheritance, chloroplast and mitochondrial inheritance, mitochondrial mutations in yeast, human genetic disorders related to mitochondrial inheritance.

L22-24: Deviations from Mendelian Genetics II: Genomic imprinting in insects, mice and man, understanding molecular basis of epigenetic inheritance, human disorders related to imprinting, Prader Willi and Angelmen syndrome, Molecular basis of Epigenetic regulation in H19 and Igf2 region, histone modification marks, Position effect variegation.

L25 & 26: Genetic control mechanisms and generation of cellular asymmetry: The lambda phage control of lytic and lysogenic phase, molecular basis of regulatory mechanisms in phage lambda.

L 27& 28: Mating type switching in Saccharomyces cerevisiae as a primer for generating asymmetry during development

Revised Syllabus: ACBR CBCS April 2018

L 29 & 30 : Sex determination in Drosophila and humans: Chromosomal basis to genetic basis, Linking sex determination and dosage compensation in Drosophila, genetic and molecular basis. X inactivation in mammals and its molecular basis, role of non-coding RNA.

L 31: Introduction to human Genetics: Pedigree analysis and basic inheritance patterns in humans.

L32 & 33: Discussion of any 2 classical papers in Genetics.

Section B: Population Genetics:

L34 & L35: Definition, aim and scope of population genetics, population structure, factors maintaining population boundaries, effective breeding size, gene pool. L36 & L37: The Hardy–Weinberg Law and its application, factors affecting the Hardy- Weinberg equilibrium. L38-41: Human polymorphism (transient and balanced), relationship between sickle cell polymorphism and malaria, other polymorphisms that may be an adaptation to malaria eg. G6PD deficiency. Duffy blood groups, thalassemia and haptoglobins. X linked polymorphism (G6PD and colour blindness). L42- L45: Natural Selection in Human Population. Non-random mating, inbreeding and its consequences. Migration and Genetics, types of migration, models to study genetic effects of migration, gene flow, effects of gene flow, admixture and natural selection, calculation of admixture. Tutorials and assessment: 3 hours.

Text and reference books:

1. Principles of Genetics by D. Peter Snustad and Michael J. Simmons. 2. Gardner Principles of Genetics. Eldon J. Gardner and D. Peter Snustad 3. Principles of Genetics by Eldon J. Gardner 4. Introduction to Genetic Analysis by Anthony J.F. Griffiths, Susan Wessler, Sean B.Carroll, John Doebley. Tenth edition 5. Introduction to Genetic Analysis by Anthony J.F. Griffiths; Susan R. Wessler; Richard C. Lewontin, Sean B.Carroll. 9th Edition 6. Original papers and review articles for Genomic Imprinting and epigenetics (To be shared with the students). 7. Genes (Current edition) Benjanim Lewin (For molecular cascade in yeast mating type)

Revised Syllabus: ACBR CBCS April 2018

8. Original papers and reviews for mating type switch in yeast, (To be shared with the students). 9. Cavalli-Sforza, LL and Bodmer, WF (1971 Ed.) The genetics of human population. San Franscisco- Freeman. 10. Relethford, J.H. (2012 Ed) Human Population Genetics. Wiley-Blackwell

(Practicals on the next page)

Revised Syllabus: ACBR CBCS April 2018

Practicals for Genetics Course; I Semester 2017-19 Batch

Semester I : Genetics Practicals Expt. Experiment Exercise No. I Selection based on Preparation of media for selection and plating Phenotype: Yeast mutants based on auxotrophy II Selection (Contd) Observation & Interpretation III Drosophila Genetics Fly media preparation, stages of life cycle, Observation of mutant phenotypes and recognition of mutants IV C.elegans as a model Media preparation and observation of developmental organism stages

V Sex determination in Induction of male development: molecular players to be C.elegans explained. VI Metaphase chromosome Demonstration of cell culture, preparation Chromosome preparation, staining & observation. Metaphase arrested cells to be provided to students. VII Development in Drosophila Isolation of Imaginal disc from wild type Drosophila Immunostaining of imaginal General staining and staining for homeotic gene dics using primary Antibody expression against homeotic protein VIII Immunostaining (Contd) Secondary Ab. Treatment and observation under florescent microscope. IX Nucleosome Analysis Isolation of nuclei from Zebrafish using sucrose cushion X Nucleosome analysis (Contd) Micrococcal Nuclease digestion & DNA extraction Analysis by Agarose gel electrophoresis XI Analysis of VNTR-Variable Prior consent of the individuals (Students) is obtained Number of Tandem Repeats by IHEC cleared Consent form. in human DNA (IHEC 50-100 microL of blood is taken by sterile pin prick. cleared experiment) Genomic DNA extraction and estimation of concentration. XII VNTR expt.(Contd) Setting of PCR with VNTR primers and analysis by Agarose electrophoresis.

NAME OF PAPER : BIOLOGICAL CHEMISTRY 1

CREDITS 4+0+2=6 Core Course Semester 1

Preamble

This course aims to bring together the various facets of introductory organic chemistry with a small overview of its applications in medicinal chemistry and biology. The course outcomes are to train students in the understanding of chemical entities which can and those which cannot be isolated such as carbocations, carbanions and free radicals. In addition to this reactions in organic chemistry are studied with a concomitant understanding of their stereochemistry which is also discussed. Heterocyclic chemistry is discussed with a view to understanding molecules which make modern day medicines.

Reactive Intermediates in Organic Reactions

L1-2 Carbocation stability,formation and reactions with examples L3-4 carbanions, pKa values, methods of formation, stability, shapes and reactions L-5-6 Free radicals their stability, methods of synthesis and reactions L-7-8 Examples of reactive intermediates with applications to biological systems, L-9-10 benzynes, carbenes, radical cations and radical anions,

Stereochemistry of Organic compounds

The definition of the following terms with suitable examples: L-11 Elementary treatment of symmetric elements, L-12 chirality, polarimetry L-13 prochirality (enantiomer, epimer, diastereomer), L-14 Absolute and relative configuration , R & S notation, L-15-16 enantiotopic and diastereotopic faces, endo and exo faces. L-17-18 Regioselective, enantioslective stereoselective and stereospecific reactions L-19 conformation of 2,3-dibromobutane, E & Z notations, L-20 cyclohexane diols

Mechanism and stereochemistry of following reactions

L-20-21 Substitution reactions L-22 addition reactions, L-23 oxidation and reduction, L-24 Elimination reactions L-25 ester formation and hydrolysis, L-26 Aromaticity, L-27 -28 aromatic and Nucleophilic substitution, L-29 -30 Woodward Hoffmann rules, photocyclization , L-31-32 concept of suprafacial and antarafacial

Asymmetric synthesis

L-33 Examples of Asymmetric synthesis involving active substrate L-34-35 Cram and Prelog rule, L-36Examples of asymmetric synthesis involving active reagents L-37Examples of asymmetric syntheis involving active catalysts L-38-39Chiral synthesis (with suitable examples) L-40 asymmetric epoxidation L-41 Sharpless asymmetric epoxidation

Heterocyclic chemistry structure, synthesis and reactivity of the following heterocycles and their significance in biology and the synthesis of medicines

L-42 furan and pyrrole L-43 thiophene and imidazole L-44 oxazole and thiazole L-45 carbazole and indole L-46 pyridine,quinoline and isoquinoline L-47 purines and pyrimidines L-48-53 synthesis of medicines involving some of the above molecules

Practicals for Organic Chemistry Semester 1 Credits 2

1. Recrystillization and Melting Determination 2. Thin Layer Chromatography (mixture of 2 compounds) 3. Thin Layer chromatography (mixture of 3 compounds) 4. Claisen Schmidt reactions 5. Infrared spectroscopy (instrumentation and spectra analysis) 6. Cannizarro reaction 7&8. Optical activity by polarimetry of known optically active compound of known concentration and hence to determine concentration of unknown sample 9. Column chromatography 10. Aldol condensation 11. Schotten Baumann reaction

Suggested reading: 1. Quantitative organic chemistry by Vogel 2. Quantitative experimental organic chemistry by Vogel

CELL BIOLOGY Ist Semester Core paper Credits: 3+1+0 = 4

Biomembranes: L1-L2. Basic structure, lipid and protein composition and their basic functions Transport of molecules across membranes.

L3. Passive and active transport across membranes.

L4-L5. Factors regulating them, ion chanells, ABC pumps of bacteria.

Tutorial and Class test

Organelles of eukaryotic cells L6-L12. Introduction basic structure and function of various organelles, ER, golgi bodies, chloroplasts, mitochondria endosomes, lysosomes etc.

L13-L14. separation and visualization methods of various cell organelles.Muscle & Nerve Cells.

Tutorial and Class test

Nucleus and Chromosome Structure L15-L17. Introduction: Prokaryotic and Eukaryotic genome and its organization, eukaryotic chromosome.

L18-L19. Basic structure of DNA; hairpins and cruciform, Z-DNA, triple helix.

L20-L22. DNA Supercoiling: Histones, nonhistone proteins, topoisomerases and telomerase and their functions in chromatin structure. Yeast artificial chromosome.

Tutorial and Class test

The Cytoskeleton L23. Cytoskeleton proteins, and Cell motility and shape,

L24. protein sorting, Transport of proteins.

L25. Microfilaments and actin filaments

Tutorial and Class test

ECM Proteins and Cell Adhesion L26. Cell-cell interaction, Cell junctions,

L27-L29. Adhesion proteins, Cell matrix interaction, Integrins, Functional role of adhesion proteins.

Eukaryotic Cell Cycle L30-L31. Cell cycle and its control: Loss of cell regulation by viral infection,

L32. checkpoints in cell cycle regulation. Tutorial and Class test

Cell to Cell Signaling L33. Introduction to cell surface receptors, and concept of receptors.

L34-L35. G-protein mediated signaling, camp, receptors tyrosine kinases, second messengers.

Cell death L36. Apoptosis, Necrosis, Proapoptotic and Antiapoptotic proteins

L37. mechanism of action Autophagy,

L38-L40. Senescence, Cell death mechanisms in health and diseases.

L41-42. Cell Differentiation

Tutorial and Class test

Cellular Stress Response L43. Stress response proteins and pathways,

L44-L45. Post translational modifications in stress response,

L46-L47. General responses to hyperthermia nutritional deprivation and other stressors.

Tutorial and Class test

Reading List

1. Molecular biology of the cell by Bruce, Alberts and Alexander Johnson and Julian Lewis, and th Martin Raff; Ed. 5 ; Garland Science; 2008. th 2. Molecular biology of the cell: the problem book by John Wilson and Tim Hunt; Ed. 5 ; Garland Science; 2008. 3. Molecular cell biology by Harvey Lodish and Arnold Berk, Chris A. Kaiser, and Monty Krieger; th Ed. 6 ; W H Freeman and Company; New York; 2008. th 4. Cell: molecular approach by Geoffrey M. Cooper and Robert E. Hausman; Ed. 4 ; ASM Press; 2007. nd 5. Cell biology by Thomas D. Pollard and William C. Earnshaw; Ed. 2 ; Saunders; 2008.

Course Outcome: a) Study more about human cells, and organelle structure and functions b) Elaborate study on types of human cells and the communication of signalling messages between cells, will develop understanding the concept of tissues and organ c) Study the mode of cell to cell communication and response can also be interperted under genotoxic stresses, which help students to study more in building the concept in disease dignosis and therapeutics

MEDICAL MICROBIOLOGY

Core paper I Semester Credits: 3+0+1 (practical) 48 lectures

Preamble

Medical Microbiology course has been formulated to impart basic and medically relevant information on the microbes (Bacteria, fungi, viruses and parasites). The microbial structure, growth and development, methods and sterilization techniques in the context of study of microbes are included. The pathogenic microbes and the diseases caused by them are included to broaden the perspective of the subject. Lastly the course deals with the problem of emerging antimicrobial resistance with reference to known pathogens. The course has been designed to get integrated practical based knowledge about medically important bacteria, fungi, viruses and parasites. The students will be able to understand the structure and function of medically important bacteria, fungi, viruses and parasites. In addition they will also understand pathogenesis, diagnosis, clinical features, virulence factors and treatment strategies of medically important bacteria, fungi, viruses and parasites.

Detailed Contents

L1-5. History and scope of medical microbiology; How bacteria are different in terms of colony morphology and pattern of arrangement. Bacterial morphology: detailed structural features of gram positive and gram negative bacteria, Staining techniques for identification of bacteria. Detailed structure and functions of various bacterial organelles, cell wall, cell membrane, ribosomes, flagella, spores, capsules, storage components, quorum sensing.

L6. Tutorial

L7-9. Techniques to study morphology of bacteria, Nutrition and condition requirements of bacteria: Macro and micronutrients, growth of bacteria , temperature, moisture and dessication, oxygen and carbon dioxide requirements of bacteria.

L10-12. Multiplication and bacterial growth and methods to study growth patterns in bacteria. Aseptic techniques, methods for pure culture isolation. Cultivation methods for bacteria. Types of Nutrient media for bacteria. Aerobic and anaerobic culture methods

L13-14. Identification of bacteria using biochemical methods.

1 L15. Tutorial

L16-17. Microscopy: History, basic principles of microscopy. Bright field microscopy and phase contrast microscopy. Florescence microscopy, Confocal microscopy, SEM and TEM.

L18-19. Disinfection and sterilization: definition, importance, Physical agents: autoclave, hot air sterilization, incinerators, pasteurisation,tyndallisation, methods of quality check. Disinfection and sterilization: Radiation and filtration tequniques, Laminar flow hoods. Disinfection and sterilization: chemical disinfectants, uses of halogen compounds, alcohol based compounds, aldehydes, detergents, heavy metals. Methods for developments and quality check of disinfectants, phenol coefficient test.

L20-21. Normal flora of human body and their significance. Nosocomial infections.

L22-24. GI tract infections: Salmonella, Shigella, Staphylococcus, E. coli, Helicobater pylori

L25. Tutorial/Test

L26-27. Microbial pathogenicity, virulence factors and their effect on pathogenesis. Chemotherapy: structure and mechanism of action of Cell wall inhibitors, antimetabolites. Antimicrobial chemotherapy, protein synthesis inhibitors, Nucleic acid inhibitors.

L28. Methods for estimation of antimicrobial activity. Mechanisms of Antibiotic resistance. Literature for new emerging antibiotics. Urinary tract infections.

L29. Tutorial

L30-31. New and re-emerging diseases. infections of the respiratory system: commensals vs infectious organisms, Diagnosis and prevalence of Cornybacterium diphtheriae in India and the world. Virulence factors of Cornybacterium diphtheria, Treatment and management of Cornybacterium diphtheriae.

L32-33. Spore formation in fungi, Economic importance of fungi. Mycoses, Tenia Versicolor, White Piedra, Black Piedra. Dermatophytes, Dermatophytidis, Candidiasis, Cryptococcosis. Opportunistic Fungi, Ostomycosis. Fungal Contaminants.

L34. Medical parasitology overview and classification of medically important parasites. Nematodes: Ascaris sp., Necator americanus.

L35. Tutorial

L36-37. Lymphatic filariasis : Wuchereria bancrofti, Brugia malayi, Mansonia ozardi

L38-39. Cestodes: Taenia solium, Taenia saginata, Diphyllobotherium latum

L40. Trematode: Faciola hepatica, Faciolopsis buskii

2 L41. Medically important protozoans: Malaria,

L42. Medically important protozoans:Trypanosoma , Leishmania

L43-44. Medically important protozoans: Giardia, Entamoeba , Toxoplasma , Trichomonas, Cryptosporidium.

L45-46. Shapes and structure of viruses, classification of viruses. Life cycle of various viruses as per Baltimore system of classification.

L47-48. Arboviruses, their genetics, pathogenesis, epidemiology, diagnosis and clinical features with emphasis on hepatits, Dengue, Zika and Chikungunya viruses.

Course outcome

Medical Microbiology is one of the foundation courses for the biomedical sciences students. Students will gain insights on the nature of various infectious agents and diseases pathologies caused by common bacteria, fungi and viruses (for eg. urogenital infections, Blood and CNS infections, fungi such as Candidiasis, aspergillosis and viruses such as hepatits, Dengue, Zika)

Reading list: 1. Topley and Wilson's Microbiology and Microbial Infections by Leslie Collier and Albert Balows and Max Sussman; Ed. 9th; 6-Volume Set; A Hodder Arnold Publication, 2000. 2. Medical Microbiology by Geo. Brooks and Karen C. Carroll and Janet Butel and Stephen Morse; Ed. 24th; McGraw-Hill Medical, 2007. 3. Microbiology by Lansing M. Prescott and John P. Harley and Donald Klein; Ed. 6th; McGraw-Hill Science, 2004. 4. Medical microbiology: a guide to microbial infections: pathogenesis, immunity, laboratory diagnosis and control by David Greenwood and Richard C. B. Slack and John F. Peuthere, ed. 17th Ed. Churchill Livingstone; 2007. 5. Fundamental Virology: Fields and Knipe, ed. Raven Press, 1991. 6. Strauss, E. G. and Strauss, J. H., “Viruses and Human Disease”, Academic Press, 2002. 7. Flint, S.J., Enquest, L.W., Krug, R. M., Racaniello, V. R., and Skalka, A. M., “Principles of Virology: Molecular Biology, Pathogenesis and Control”, ASM Press. 2000.

3 MEDICAL MICROBIOLOGY PRACTICALS

I Semester Credits: 1

Detailed practicals

1-3. Demonstration of sterilization techniques related equipments and use of aseptic techniques for preparation of pure cultures. Plating methods and identification of colony morphology of key bacteria.

4-6. Demonstration of differential staining techniques like Gram’s staining, AFB staing, sporestaining etc. Differentiation of flagellate vs nonflagellate bacteria.

7-8. Differential diagnosis of bacteria based on biochemical tests.

9-10. Spread plate technique and antibiotic sensitivity assay.

11-12. Identification of medically important fungi.

4 A-PDF Merger DEMO : Purchase from www.A-PDF.com to remove the watermark

HUMAN PHYSIOLOGY-II Core paper III Semester Credits: (3+1+ 0)

PREAMBLE:

In continuity to understand the physiology of various organ systems in Human physiology-II, we ought to understand two of the vital organ system i.e. cardiovascular and nervous system. These system are vital as cessation in the functioning of any of these system straight away leads to death, therefore these system are dealt in detail along with their inter-relationship with other organ systems.

UNIT 1: Cardiovascular system L1-4: Physiology of cardiac muscle (contractile and auto-rhythmic myocytes), Cardiac Cycle Control and Regulation of excitation, contraction and conduction of heart pumping, Heart sounds L5-10: Characteristics of normal electrocardiogram, analysis of ECG for various myopathies, Cardiac arrhythmias L11-14: Physical characteristics and basic theory of circulation, Vascular dispensability and functions of arterial and venous systems, Microcirculation and lymphatic system, Capillary fluid exchange, interstitial fluid and lymph flow, Local control of blood flow by tissues and humoral regulation, Nervous regulation of circulation, Cardiac output, venous return and their regulation, coronary circulation. L15-18: Blood and circulation: blood corpuscles, haemotopoiesis and formed elements, plasma function, Hemostasis and blood coagulation, Blood banking, blood groups, and Transfusion.

Tutorial: Group discussion, Student seminar and test

UNIT 2: Overview of the Nervous System L19-22: Neuron and classification of nerve cell, nerve fibers, nerve, intracellular trafficking of neuron, Resting membrane potential of nerves, Nerve action potential, neurotransmitters: synthesis, models of exocytosis of synaptic vesicles and its inhibitors, synapse: types, pre and post synaptic regulation. L23-25: Anatomical and functional division of nervous system, Spinal cord and cranial nerve, Blood-Brain barrier, Cerebral Blood Flow, Regulation of Cerebral Circulation.

Tutorial: Group discussion, Student seminar and test

UNIT 3: Motor System L26: Motor Units, Motor neurons types and characteristic of upper and lower motor neuron, lesions of upper and lower motor neuron. Muscle Receptors, L27-29: Posture: Neural Systems Controlling Postural Orientation and Stability, Automatic Postural Reactions, Postural Reflexes: Infant to Adult, Spinal Reflexes. Grouping of Motor pathways: direct and indirect pathways, Cortical and brain stem control of motor function.

Tutorial: Group discussion, Student seminar and test

UNIT 4: Cognitive System L30: Neural Basis of Instinctual Behavior & Emotions: Limbic Functions: behavior, Sexual Behavior, Fear & Rage, Motivation

Tutorial: Group discussion, Student seminar and test

UNIT 4: Learning and Memory L31-33: Cerebral Cortex: Intellectual functions of brain, learning and memory, Physiologic anatomy of cerebral cortex, Functions of specific cortical areas, Association areas, Function of brain in communication - language input and output, Function of corpus callosum and anterior commissure. L34-35: Thoughts, consciousness and memory: Memory formation, types of memory, molecular pathway of memory formation, Activating-driving systems of brain, Functional anatomy and functions of limbic system and hypothalamus, States of brain activity, Brain waves, Origin in brain of brain waves (EEG). L36-37: Sleep: Slow-wave sleep, REM sleep, Basic theories of sleep and awake, Physiological Mechanisms of Sleep and Waking, dreams sleep deprivation, Epilepsy, Psychotic behavior and dementia - roles of specific neurotransmitter systems.

Tutorial: Group discussion, Student seminar and test

UNIT 5: Sensory Physiology L38-39: Neuronal circuits for processing information, “Coding” of Sensory Information, Electrical & Ionic Events in Receptors. L40-41: Somatic sensations: Tactile and position senses, Sensory pathways for transmission of somatic signals into the central nervous system, Sensory receptors, Transmission in dorsal column – medial lemniscal system. L42-43: Pain and thermal sensations: Pain receptors and their stimulation, Dual transmission of pain signals into the central nervous system, Types of pain.

Tutorial: Group discussion, Student seminar and test

Special Senses L44-45: Eye: The Image-Forming Mechanism (accommodation and visual acuity), Receptor and Photochemistry of vision, Neural function of retina. Visual Pathways and effects of lesions of these pathways L46-47: Hearing and equilibrium: Tympanic membrane and ossicular system, Cochlea, Central auditory mechanisms, directionality of sound, Vestibular sensations and maintenance of equilibrium, auditory and vestibular reflexes, oculo-vestibular system L48: Taste and smell: Anatomical aspects of olfaction and gustation, Receptors and sensory transduction of olfaction and gustation & Neuronal Pathways of olfaction and gestation

Tutorial: Group discussion, Student seminar and test

UNIT 6: The Autonomic Nervous L49: System Introduction Anatomic Organization of Autonomic Outflow Chemical Transmission at autonomic Junctions Responses of Effector Organs to Autonomic Nerve Impulses Cholinergic and Adrenergic Discharge.

Tutorial: Group discussion, Student seminar and test

Central Regulation of Visceral Function L50: Hypothalamic Function: Autonomic Function, Cyclic Phenomena and circadian rhythm, Hunger Thirst Control of Posterior Pituitary Secretion Control of Anterior pituitary Secretion Temperature Regulation, fever.

Tutorial: Group discussion, Student seminar and test

COURSE OUTCOME Human physiology II: This course is a core course and continuation of Human physiology I to be offered in third semester. On satisfying the requirements of this course, students will have the knowledge and skills to: 1. Describe the anatomy and histology of nervous system and cardiovascular system. 2. Understand the indications for, interpretation of, and risks of the common cardiovascular testing modalities for normal and diseased state 3. Become familiar with the emergency sign and symptoms in case of cardiac/ nervous system dysfunction. 4. Be aware of the i) symptom and approach knowledge, ii) disease based knowledge for nervous system dysfunction 5. Create awareness for the importance of healthy mind and heart.

Reading list:

1. Textbook of medical physiology by Arthur C. Guyton and John E. Hall; Ed.13th & 14th. 2. Review of medical physiology by William F. Ganong; Ed. 23nd ; McGraw Hill; 2010. 3. Essential medical physiology by Leonard R. Johnson and Ed. 3rd; ELSEVIER; 2003. 4. Principles of anatomy and physiology by Gerard J. Tortora and Bryan Derrickson; Ed.15th; John Wiley; 2016. 5. Hole's Human Anatomy & Physiology , McGraw-Hill Education; 14 edition, 2015 6. Medical Physiology: A cellular and molecular approach by Walter F. Boron and Emile L. Boulpaep; Saunders; Ed. 3rd , 2017. 7. Physiology by Robert M. Berne and Matthew N. Levy; Mosby; ELSEVIER, Ed.7th 2018. 8. Principles of Neural Science, (Kandel) 5th Edition, 2013. 9. Fundamental Neuroscience, ELSEVIER 4th Edition, 2012 10. Neuroscience Online, an Open-Access Neuroscience Electronic Textbook https://nba.uth.tmc.edu/neuroscience/

M.Sc. 3rd Semester

PRINCIPLES OF MEDICINAL CHEMISTRY 60

CORE COURSE

CREDITS 3+1

Preamble The course includes theoretical studies in the field of Medicinal Chemistry. This encompasses the denovo approach to design of drug candidates, the potential physico-chemical interaction between low molecular-weight compounds and biomolecules such as proteins and DNA, plausible biochemical transformations for elimination of small molecules. In addition, few examples of rational drug design to target specific protein/ receptor for the human pathologies such as peptic ulcers, hypertension, atherosclerosis, cancer, neuronal pathologies etc. will be studied. Thus, the course includes theoretical elements concerning the identification, design, synthesis and evaluation of low molecular organic substances for specific pathological state from the perspective of medicinal chemistry.

Expected outcomes

After completing the course, students shall be able to: - describe the various steps involved in the design of a drug, - describe the "interaction between ligand and receptor" concept - identify and describe the connection between chemical structure and physical-chemical properties, - describe the design of organic compounds, for example, statistical or structure-based design, - in groups, plan and conduct a medicinal chemistry project, - independently acquire and critically assess biological and medicinal information from databases, - actively participate in discussions during seminars and group exercises, - present results verbally and in writing, and - communicate principles, problems and research results with specialists and non-specialists on issues within the scope of the content of the course.

COURSE CONTENTS

1. Role of Medicinal Chemistry in discovery of drugs

L1- L2 Introduction to medicinal chemistry as a strategy to the design of new drug candidates for the human pathologies.

2. Drug Design

(a) Discovery of lead compound-

L3- L4 Serendipous, Random and Non-random screening, drug metabolism studies, clinical observations L5- L6 Rational approaches to lead discovery- Homologation, chain branching, ring-chain transformations, bioisosterism.

(b) Lead modifications

L7- L8 Conventional drug screening and structural modifications, concept of isosteres and bioisosteres, structure activity relationship,

L9-10 Quantitative structure activity relationships- Electronic effects: Hammett equation, lipophilicity effects. Hansch equation, stericeffects.

L 11-12 Taft equation, mathematical method for denovo design, Mannual stepwise scheme 2D QSAR; 3D-QSAR examples, CoMFA c. Introduction to molecular modeling and molecular graphics, pharmacophore descriptors

L 13 The classical mechanics model (e.g., MM1, MM2),Quantum chemical methods semi-empirical and ab initio methods.

L 14 Molecular graphics: View and manipulate molecular structures

L 15-16 Pharmacophore descriptors: Based on Genetic Algorithms--Partial Least Squares (GA-PLS) and K- Nearest Neighbors (KNN) to achieve a robust QSAR model characterized by the highest value of cross- validated R2 (q2).

3. Receptors

Chemical nature of receptors

L17-18 Covalent, ion-ion, ion-dipole, Hydrogen bonding, C-H hydrogen bonding, dihydrogen bonding, Van der Waals interactions and the associated energies, Chirality and receptor binding.

Drug receptor interactions

L19-20 Occupancy Theory, Rate Theory, Induced Fit Theory, Macromolecular perturbation theory, Activation-Aggregation theory.

L21-22 Classification of receptors and receptor subtypes, Neurotransmitters and their receptors, Receptor modulation and mimics, Receptor sites.

L23-24 Chirality and receptor binding, Signal transduction and second messenger systems.

L25-28 Active transport, affinity and efficacy, antagonism, partial antagonism, inverse agonism, allosteric binding sites.

4. Introduction of various classes of drugs based on their interaction with target site.

With suitable examples, the drugs interacting with L 29-30 (i) Receptors-Rational design of agonist/antagonist

L 31-32 (ii) Enzymes Mechanisms of enzyme catalysis, Electrostatic catalysis and desolvation. Covalent catalysis, Acid-base catalysis, Strain / distortion in enzyme catalysis. Coenzyme catalysis.

L 33-36 (iii) Enzyme Inhibition-Reversible and irreversible, rational design of various enzyme inhibitors, Adverse drug reactions, Drugs acting on cell wall, Fungal membrane and Nuclear membrane, Drugs inhibiting protein synthesis.

L 37-40 (iii) DNA- NA as targets for drug action. NA-interactive agents. Classes of drugs that interact with nucleic acids. Intercalation, NA-alkylation, NA-strand breaking and their importance in drug action,

L 41-42 (iv) Carbohydrates- development of glyco-conjugates in cancer models

5. Structure activity relationship illustrated with examples from

L 43-44 Sulphonamides, b-lactams, Quinolones, Nucleosides and Alkaloids.

6. Drug Metabolism

L 45 (i)Biotransformations and their Mechanisms

L 46-48 (ii)Phase I and Phase II metabolism, Oxidation, Reduction, Hydrolysis, Deamination and Conjugation (GSH, Sulfate, Glucuronide and Amino acids)

L 48-50 (iii) Role of non-specific enzymes: Oxidases, Mono-oxygenases, Di-oxygenases and Peroxidases, L 51-52 (iv) Biotransformations illustrated by suitable examples of commonly used drugs, Chirality and drug metabolism.

L 53-60 Tutorials/ discussions

Reading List

1. Organic chemistry of drug design and drug action by Richard B. Silverman; Ed. 2nd; ELSEVIER; 2004.

2. Foye's Principles of Medicinal Chemistry by Thomas L Lemke and David A Williams; Ed. 6th; Lippincott Williams & Wilkins; 2007.

3. Medicinal chemistry: principles and practice by Frank D. King; Ed. 2nd; The Royal Society of Chemistry; 2002.

4. Introduction to Medicinal chemistry by Graham L. Patrick; Ed. 3rd; Oxford; 2006.

Pharmacology and Toxicology

Core paper

IIIrd Semester

Credits: (3+1+2=6)

Preamble

The course develops the understanding of theoretical and practical studies in the field of Pharmacology and Toxicology. The course involves the building up the knowledge of pharmacokinetic and pharmaco-dynamic profile of drug, pharmacological classification and principle of drug action and the types of toxicity assessments of various type toxicants of chemical and biological origin and environmental pollutants on organ system and drug disposition.

Introduction to pharmacology

L1. Scope of pharmacology: Introductory class to define pharmacology, historical background and limitations

Pharmacokinetics

L2-L3. Absorption- Routes of administration of drugs, their advantages and disadvantages. Various processes of absorption of drugs and the factors affecting them

L4-L5. Metabolism i) Microsomal and non-microsomal mechanisms ii) Effect of Enzyme induction and inhibition on drug metabolism and the factors influencing them.

L6-L9. Distribution - i) distribution of drugs and the factors affecting them ii) Loading and maintenance doses Excretion of drugs- i) zero order, first order and steady state kinetics and half life of drugs, Numerical problems Pharmacodynamics: General mechanism of drug action and the factors, which modify drug action. : i) Dose response relationship curves and different types of antagonisms.

Pharmacodynamics

L10-L12. i) General mechanism of drug action and the factors, which modify drug action (signal transduction mechanisms in general. Dose-response relationship curves and different types of antagonisms. ii) Drug receptor interaction and Theories.

Pharmacological classification of drugs; the brief introduction of drugs should emphasize the ADME profile of following systems

L13-L14. Drugs acting on the central nervous system: Anesthetics- History, theory, mechanism and stages of anesthesia, Drug classification based on mechanism of action of anesthesia, Inhalation and general anesthesia; Local anaesthetics-classification and mechanism of local anesthesia, adverse reactions of Anesthesia

L15-L16. Pshychopharmacological agents: Sedatives, Hypnotics, anxiolytics, anti-mannaic, antidepressants

L17-L19. Drugs acting on the autonomic nervous system: Cholinergic drugs, anticholinergic drugs, anticholinesterase drugs, dopaminergic drugs, Adrenergic drugs and adrenergic receptor blockers, Neuron blockers and ganglion blockers, Neuromuscular blockers, drugs used in myasthenia gravis.

L20-L21. Cardiovascular drugs, cardiotonics, antianginal agents, antihypertensive agents, peripheral vasodilators and drugs used in atherosclerosis, coaogulants and anticoaogulants.

L22-L26. Drugs acting on the respiratory system, Expectorants and antitussive agents, Drugs acting on the digestive system, Drug acting on Renal system, Coaogulants and anticoaogulants, Analgesics- Opiod analgesics (Morphine) and NSAIDs (Brufen)

L28. Hormones and hormone antagonists (Classification of hormones based on their pharmacological and physiological action), Mechanism of hormonal action (Hypothalamopituitary adrenal / thyroid axis).

L29-L30. TUTORIALS & CLASS TEST

Principles of Toxicology

L31-L34. Definition, scope and different branches of toxicology. A brief review of toxic substances: Synthetic organic compounds: Chemical additives in food, Chemicals in the work place, Solvents, Pesticides, Cosmetics, Drugs of abuse. Inorganic chemicals: Industrial and chemical environmental inorganic toxicants polluting air/ water/ food. Naturally occurring poisons: Mycotoxins, Bacterial toxins, Plant toxins and Animal toxins.

Types of toxicity and its measurement

L35-L39 Acute, Sub-acute or Chronic and its manifestations. Acute toxicity: Mode of application/ administration/ exposure, in-vitro tests, Dose response relationship, Measurement of TD 50/ TC 50 and LD 50/ LC 50. Sub-acute and chronic toxicity. Risk and safety analysis: Margin of safety, Therapeutic index, Ideal therapeutic index. Inter-species extrapolation of dose-response data, NOEL, ADI, TLV, WHO standards. Special toxicity studies: Carcinogenecity, \\ teratogenicity, in-vitro mutagenicity tests.

Epidemiology of toxicity

L40-L42. Cohort study, Retrospect study, Case-control study, Cross-sectional study, Confounding.

Pharmacokinetic aspects of toxicants

L43-L44. Site of metabolism, Metabolizing enzymes of liver, kidney, lung, GI tract, skin and their role in activation and detoxification of drugs and chemicals. Physiological (route of exposure, species, sex and age), Nutritional and environmental (temperature, altitude and circadian rhythms related) factors affecting metabolism, detoxification and toxic responses of drugs and chemicals.

Organ toxicities

L45- L48. Hepatotoxicity: A brief description of morphological and functional aspects of liver with special reference to hepatotoxicity, various hepatotoxic agents, types of liver injuries- Fatty liver formation, Necrosis, Cholastosis, Hepatitis, Fibrosis, Cirrhosis, Carcinogenesis.

L49-L50. Nephrotoxicity: A brief description of morphological and functional aspects of kidney in relation of nephrotoxicity, nephrotoxic agents, detailed mechanisms of chemical induced nephrotoxicity.

L51-L52. Cardiovascular toxicity: A brief description of mechanisms of cardiovascular toxicity and cardiotioxic agents- subcellular and biochemical mechanisms.

L53-L54. Neurotoxicity: A brief description neurotoxic agents and types of neurotoxic effects- Axanopathy, Neropathy, Neuronopathy, Mylenopathy. Broncho-pulmonary (inhalation) toxicity.

L55.Gastro-intestinal toxicity.

L56.Skin toxicity/ photosensitivity.

Tests for evaluation of toxicities in different organs

L57-L58.Therapeutic aspects: General measures and treatment of poisoning cases, Specific antidotes, Agents of first choice, Contraindications.

L59-L60. TUTORIALS & CLASS TEST

PHARMACOLOGY & TOXICOLOGY (Practicals)

1. CPCSEA guidelines for animal experiments, Animal handling and precautions.

2. To study the different routes of administration in different animal models.

3. Preparation of buffers and reagents require for the forthcoming experiments.

4. Topical application of Atropine and Pilocarpine on rabbit eye

5. Analgesic effect of diclofenac on mice/rat.

6. Study the effects of acetylcholine (Ach) and plot the dose-response curve.

7. Study the effect of general anaesthesia with ketamine in rat.

8. Study the haloperidol induced PD-like symptoms in mice.

9. To determine the effect of promethazine on phenobarbitone induced sleeping time in mice.

10. To determine the acute toxicity of a given drug and calculate the LD50 value.

11. Detection of organophosphorous pesticides in biological sample.

12. To test the presence of paracetamol in the given biological sample.

13. To determine the lethal concentration of Arsenic in Zebra fish according to OECD guidelines.

14. To determine the lethal concentration of Copper in Zebra fish according to OECD guidelines.

15. To identify plants which are toxic to human and animals in a given set up of garden or farm field.

READING LIST

1. Essential of medical pharmacology; 6thEd. By K.D. Tripathi; Jaypee Brothers; New Delhi; 2008. 2. Goodman & Gilman’s the pharmacological basisof therapeutics by Laurence Brunton and John Lazo and Keith Parker; Ed. 11th; McGraw-Hill Professional; 2005. 3. Pharmacology H. P. Rang and M.M. Dale and J.M. Ritter and P.K. Moore; Ed. 5th; Churchill Livingstone, 2003.

4. Integrated Pharmacology: With Student Consult Accessby Clive P. Page and M.J. Curtis and M.C. Sutter and M.J. Walker and B.B. Hoffman; Ed. 3rd; Mosby; 2006. 5. Principles of toxicology by Karen E. Stine and Thomas M. Brown; Ed. 2nd; CRC Press; 2006. 6. Lu’s basic toxicology: fundamentals, target organs and risk assessment by Frank C.Lu and Sam Kacew; Ed. 5th; Informa Healthcare; 2009. 7. Casarett and Dull’s toxicology: the basic science of poisons by Curties D. Klaassen; Ed. 7th; McGraw Hill; New York; 2007. 8. Toxicology by Hans Marquradt and S.G. Schafer and R.D. McClellah and Academic Press; 1999. 9. Principles and practice of toxicology in public health by Ira R. Richards; Jones and Bartlett Publishers; 2007. 10. Handbook of human toxicology byE.J. Massaro; CRC Press; 1997.

Course outcome

After completing the course, students shall be able to:

- describe the various steps involved in the interaction of a drug to its target,

- Administer the drug through various routes to the rats or mice and do toxicity assays.

- describe the pharmacokinetic and toxicokinetic profile of the drugs and chemicals respectively,

- Describe the design of treatment strategy - in animal group,

- plan and conduct a pharmacology project and toxicological assays,

- Independently acquire and critically assess Pharmacological and Toxicological information from databases

ANALYTICAL & BIOMEDICAL TECHNIQUES AND INSTRUMENTATION CORE COURSE IIIrd Semester Credits (3 + 1 = 4) 60 lectures

Preamble: The course on Analytical and Biomedical Techniques and Instrumentation will be offered as CORE course in the 3rd Semester and covers various techniques used in analytical and Biomedical analysis. The course will be able to make students understand theoretical basis of these techniques as well as train them in handling various instruments and analysing the data. The students will be given hands on training to learn these techniques and apply the knowledge in developing skills which are essentially needed to work in clinical diagnostic and research laboratories in the field of biology and analytical biochemistry. The course has been designed to make them gain theoretical knowledge, practical handling of instruments and analysing the results obtained from these techniques for biomedical research.

Introduction 1 Lecture

L1 Principles of Instrumental Analysis, Types of Instrumental Methods to be covered in the course. Selecting an analytical method and developing a new Analytical Technique.

Optical Methods and their applications in Biomedical Sciences 11 Lectures

L2-3. Ultraviolet / Visible molecular absorption spectroscopy, Theoretical basis, transitions, Lambert’s Beers Law, factors affecting Absorption, L4-5. Fluorescence and Phosphorescence (principle Jablonski diagram), Fluorescence quenching (dynamic, static, Sterm volmer constant, FRET with examples from Biomedical field. L6-7. Biomolecular interactions using spectroscopic methods L8-9. Infrared – vibrational spectroscopy introduction, Functional group identification, Effects of various factors on IR frequencies and biomedical application. L10. Concept of circularly polarized light and principles of CD L11. CD instrumentation, concepts of band width, slit width, scan speed, and other factors in getting proper resolution of bands L12. Application of CD in macromolecular structure determination, binding studies and other applications

Separation Methods 4 lectures

L13–16. An introduction to chromatographic separation, Gas Chromatography, Pressure Liquid Chromatography and FPLC, Supercritical fluid chromatography

Nuclear Magnetic Resonance Spectroscopy 10 Lectures

L17-19. Theory of NMR: Quantum description, Classical description – Processional motion, Larmour frequency, Relaxation processes, T1 and T2 and their measurement. Fourier Transform NMR: Pulsed excitation, FID, Types of NMR Spectra – Wild line and high - resolution spectra. L20-21. NMR Spectrometers: Instrumentation. Environmental Effects: Types, Chemical shift theory, Magnetic anisotropy, L22-24. Spin–spin splitting, first order and second order spectra, Double Resonance Techniques, Proton on heteroatom. Application of proton NMR: Identification of compounds. L25-26. Introduction to 13C NMR: Proton decoupling: Broad band, off-resonance, Pulsed decoupling, NOE, application to structure determination.

Magnetic Resonance Imaging: 6 Lectures

L27-28. The concept of MRI, BOLD imaging, fMRI, L29- 30. Application in Muscle Physiology, functional mapping of brain. L31-32. Other nuclei : 31P, 19F, 23Na, 15N, metabolomics studies using NMR

Mass Spectrometry 6 lectures

L33-35. Introduction to mass Spectrometry. Forming charged particles: Electron impact (EI) and Chemical Ionization(CI), Fast Atom Bombardment (FAB), Field Desorption (FD), Electrospray Ionization, Matrix Assisted Laser Desorption Ionization (MALDI). L36-37. Mass Analyzers: Magnetic sector mass spectrometers, Double focusing mass spectrometers, Quadrupole pole mass spectrometers, ion cyclotron resonance, Time of Flight mass analyzers. Combine the mass spectrometer with Gas Chromatography (GC/MS) and with liquid chromatography (LC/MS). L38. Applications of mass spectrometry in Biomedical field- Peptide mass fingerprinting, protein sequencing using MASS spectrometry.

Flow Cytometry, Magnetic Assisted Cell Sorting: 4 lectures

L39. Introduction to flow cytometer: Need and versatility of FACS. Fluidics and Optics in FACS L40& 41. Filters and detectors in FACS: choosing the right fluorochromes, compensation of overlapping emissions L42. Plotting of data in various formats (Histograms/dot plots/ contour plots) Gating, Principles of cell Sorting by FACS and MACS

Miscellaneous TECHNIQUES 5 Lectures

L43. Confocal Microscopy: Applications in Cell Biology, Electron Microscopy, L44-46. Tracer Techniques in Biology: tumor diagnosis and imaging, infectious diseases such as tuberculosis. L47-48. Biomolecular Structure determination techniques: X-Ray crystallography.

Tutorial classes/class tests/ discussion periods 12 lectures

Course Learning Outcomes

• The students of the course will be able to learn theoretical basis of various analytical and biomedical techniques. They will be trained in spectroscopic techniques such as UV-Visible, Infrared, Fluorescence, Circular Dichroism and their applications in the field of Biomedical Analysis. • Students will learn analytical separation techniques such as Gas Chromatography, High Performance Liquid Chromatography, Supercritical Fluid Chromatography. • Students will understand theoretical basis of Magnetic Resonance Spectroscopy (MRS) as well as Imaging (MRI). They will be able to understand the application of NMR in the field of drug analysis and diagnosis using MRI etc. • Students will also learn about MASS spectroscopy and its application in the field of analytical and biomedical research. Students will be able to solve structures of small drug molecules based on analytical data based on IR, NMR and MASS spectroscopic techniques. • Students will be able to analyse and interpret results obtained from fluorescence assisted flow cytometry (FACS), confocal microscopy and tracer techniques in this field.

Reading List

1 Spectrometric identification of organic compounds by Robert M. Silverstein and Francis X. Webster; Ed. 6th; John Wiley; 1997. 2 Principles of instrumental analysis by Douglas Skoog and F. James Holler and Timothy A. Nieman; Ed. 5th; Saunders; 1998. 3 Contemporary instrumental analysis by Kenneth A. Rubinson and Judith F. Rubinson; Prentice Hall 2000. 4 Organic spectroscopy by William Kemp; Ed. 3rd; Palgrave; 1991. 5 Basic one and two dimensional NMR spectroscopy by Horst Friebolin; Ed.3rd; Wiley- VCH; 1998. 6 Principles of Fluorescence Spectroscopy by Lacowicz, 3rd Ed. 2006, Springer US. 7 NMR and its applications to living systems by David G. Gadian; Ed. 2nd; Oxford; 1995. 8 Structure determination of organic compounds: tables of spectral data by E. Pretsch and P. Buhlmann and C. Affolter; Springer; 2005. 9 MRI principles by Donald G. Mitchell; W S Saunders; 1999. 10 HPLC: a practical user’s guide; Ed.2nd by Marvin C. McMaster; Wiley-Interscience; 2007.

Practicals

Course: ANALYTICAL & BIOMEDICAL TECHNIQUES AND INSTRUMENTATION Semester IIIrd Credits 2

1. To verify Lambert Beer’s law and calculating concentration of unknown analyte a. using UV-VIS spectroscopy. b. Fluorescence spectroscopy 2. To study interaction of intercalating agents like ethidium bromide with DNA using: a. UV –visible spectroscopy. b. Fluorescence spectroscopy. 3. Studying and analysing CD spectrum of a protein 4. To study the Conformation change of Biomolecule using CD spectroscopy. 5. Infra-red Spectroscopy. Recording and interpretation of IR of a metabolite. 6. HPLC- introduction to the working of the instrument and analysis of a sample. Calculating concentration of unknow sample from standard surve 7. Separation of two samples using HPLC using isocratic and gradient mobile system. 8. Mass Spectroscopy: Identification of a biopolymer using MALDI/ LC-MS. 9. NMR: 1H and 31P spectroscopy of muscle physiology during exercise and calculation of pH change from spectra. 10. Spectral Identification of a simple organic compound/metabolite/drug. (two examples) 11. Flow Cytometry: a. Cell cycle analysis b. To monitor real time influx in intercellular calcium levels

Course specific learning outcome (Practicals)

• At the end of this course student will be able to able to instruments such as UV-VIS, Fluorescence and CD spectrophotometer. • They will be able to analyse samples using HPLC and flow cytometer. • The students will also learn how to analyse characterization data of given unknown compound and interpret its structure from the data. • They will also learn to study the biomolecular interactions using the spectroscopic techniques, analysing secondary structure of a biomolecule etc.

MOLECULAR ONCOLOGY

ELECTIVE paper in III semester

Credits 4 (4+0+0)

Preamble: With increase in incidence of cancer in our country, it is considered important to have a basic background of molecular basis of cancer. The students will be taught various risk factors and types of cancer. Basic concept of mechanism of carcinogenesis will be taught wherein important proteins and pathways will be taught. At the end of the course some of the research papers related to these topics will be presented and discussed in the class.

The Cancer Problem L1: Introduction to Cancer, Global and Indian incidence, various types of cancers, Epidemiology, L2: Environmental carcinogens, chemical and physical carcinogens types with examples. L3: Various risk factors, life style, changing patterns, the Indian scenario.

Mechanisms of Carcinogenesis

L4: Various theories, multi-step and multistage processes, concept of transformation L5: Initiation, Promotion and Progression of cancer. L6: Role of DNA damage, repair and mutations by physicochemical agents and viruses, L7: Interaction of various agents in cancer L8: Differentiation: hyperplasia and precancerous lesions. Strategies of chemoprevention.

L 9: TUTORIAL CLASS L10: TEST (10marks)

Tumor types and leukemia

L11: Benign and malignant tumors, localized and metastatic disease L12: Schemes of classification, WHO classification, staging and grading, degree of malignancy. L13: Introduction to leukemia, Classification of leukemia, types of chromosomal translocations. Examples of common types based on prevalence. L14: Diagnosis of leukemia (Flow cytometric method, qPCR).

Modulation of the Eukaryotic Cell Cycle and cell death in cancer L15: Cell cycle and check points, role of kinases, L16: Mechanism of deregulation of cell cycle during cancer. Various proteins involved and their mechanism L17: Apoptosis, and Necrosis regulation in normal cell and dysregulation in cancer L18: Proapoptotic and Antiapoptotic proteins and mechanism of action in controlling apoptosis. L19: Methods used to study apoptosis (western, Flow cytometry, tunnel assay) L20: methods contd, Cellular senescence

L21: TUTORIAL CLASS L22: CLASS TEST 2 (Marks 10)

Cell-cell Interactions in Development of cancer L23: Cell-cell interaction, integrins, and other proteins involved in cellular adhesion. L24: Concept of invasion, changes in cellular proteins. L25: Mechanism of invasion by cancerous cells. L26: Metalloproteases and their role in cancer metastasis L27: Methods to study invasion in vitro. L28: Tumor microenvironment, interaction between malignant and normal cells L 29: Research papers presentation L30 Research Papers presentations and Discussion

L31: Test based (Marks 10)

ANGIOGENESIS: L32: Angiogenesis and various factors involved in angiogenesis L33: Molecular mechanism of angiogenesis L34: Concepts and molecular mechanism of Neoangiogenesis in cancer L35: Methods to study angiogenesis.

L 36: Tutorial Research papers discussion on angiogenesis

Tumor suppressor genes and Viral oncogenes L37: Concept of tumour suppressor proteins and oncoproteins. transformed cells and immortal cells. L38: Mechanisms of action of P53 in cancer L39: Mechanisms of action of P53 in cancer contd L40: Role of other members of p53 protein in cancer L 41: Tutorial on Research papers discussion related to P53 isoforms. L42: Role of RB proteins in cancer L43: Altered mechanisms of action of Rb protein in cancer cells L44: Other tumour suppressor proteins, BRCA1, BRCA2, APC and WT1, Mismatch repair proteins L45: Oncoproteins and their examples, Basic concept of proto-oncogene, discovery, gain of function mutations etc. methods to identify. L46: Role and mechanism of viral oncogenes with 1-2 examples. L47: understanding the role of large Tantigen, HPV in cervical cancer. L48: Role of cellular oncogenes in altered gene regulation (basic mechanisms of action) L49: Mechanism of action of oncogenes contd using specific examples: jun-fos, Ras L50: condt. AML-ETO etc in gene regulation.

L51: Research paper presentations and discussion L 52: Research paper presentations and discussion L 53 Research paper presentations and discussion L54: Test (Marks 10)

Growth factor-signalling pathways in cancer L55: Relationship between oncogene products and growth factors, L56: Understanding altered pathways using example of receptor kinases, Src, Wnt signalling L57: Abl, cKit, Rho and Ras factors L58: GAP and growth factors. L59: Effect of viral infection on signal transduction. L60: Tyrosine kinases and inhibitors

L 61: Research paper presentations and discussion L62: Research paper presentations and discussion L63: Research paper presentations and discussion

COURSE OUTCOME:

By the end of the course students will be familiar with common carcinogens and how life style can contribute to increase in cancer incident. They will also be aware of various steps and different mechanisms that form the basis of differences in cancer progression and drug response. A basic understanding of various techniques that can be used so as to do decipher these pathways and to identify the proteins involved in cancer will help them in pursuing research in this important area.

ACBR, CBCS April 2018

Stem Cell Biology for developmental and translational research (III Semester Elective Course, Credits 3+1)

Members of the sub-committee: Dr. Manisha Yadav, Dr. Richa Arya, Prof. Vani Brahmachari. Feedback received from: Dr.Maneesha Inamder, JNCASR, Dr.Jyotsna, InStem, Prof. B.C. Das

Preamble: This course is conceived in the light of relevance of stem cells to biomedical research. The natural process of development is the journey of living organisms from totipotency to pluripotency and further to differentiation towards functional specialization to make a complex and self-propagating system . Therefore the course begins with the concepts of developmental biology, the unification of molecular mechanisms across phyla is emphasised. The course tries to bring out how this knowledge also gives us the ability to reverse the process to address important aspects of human health.

Course outcome: • The students will gain an understanding of common theme and the varied strategies of development that nature has evolved by the comparison between different systems • The students will be aware of the characteristics of stem cells and the limitations in the use of stem cells. • They will appreciate how nature has preserved the mechanisms invented at various stages of evolution. • They will be aware of the tools used in stem research, the ethical issues involved in the application of stem cell usage in medical research. • Throughout the course the students will be exposed to original papers that led to the various discoveries that have kindled the enthusiasm and hope of use of stem cells in health sciences.

L1 - 3: Introduction: what are stem cells ( embryonic stem cells, adult stem cells, iPS), History of stem cell research, Differentiated cell vs stem cells, What determines stemness, scope of stem cells to cure disease, Early experiments on stem cell and regeneration. Cloning and aging issues (Dolly, etc..), what we do not know about stemness (discussion to introduce importance of learning developmental biology).

Journey from stemness to differentiation I; L4- 5: Insights from Drosophila model: Early embryonic development, Maternal inheritance, L6-8: Genetic basis of axis determination, pattern formation, regulatory cascade in development in Drosophila, L 9 & 10: Homeotic genes and their regulation.

L11-12-Student Seminar

Journey from stemness to differentiation II; L13-14: Amphibian development: Xenopus development as a model, Salient feature of amphibian development

ACBR, CBCS April 2018

L15: Positional information in development- the 'Organizer ' concept, cell-cell interaction in development, L16-17: Concept of morphogen gradients, their generation and effect on development.

Journey from stemness to differentiation III; L18-19; Mammalian development: Salient features of Mouse and Human embryonic development as examples of regulated development, generation of mosaic embryos. L20: Pattern formation example of limb development.

L21-22: Conservation of pathways of development and differentiation across phyla with example; Notch, Wnt, Hippo, discovery and evolutionary conservation (the teacher may choose one of the examples to illustrate the concept)

L23-25: Molecular basis of stem cell renewal and differentiation, Metaplasia and trans- differentiation. Molecular basis of pluripotency and stem cell niche and reprogramming.

L26-27- Student Seminar

L28-31: Reversing differentiation by reprogramming: (i) Developmental reprogramming, regeneration "Young all the Time!"; Planaria, Hydra, earthworm. Induced pluripotent Stem cells (iPSCs).

L32-35: Overview of tools for stem cell research: Isolation & characterizations, markers & their identification, growth factor requirements and their maintenance in culture. Cell cycle regulators in stem cells

L36-38: Ethical issues related to stem cell research; Ethics in use of stem cell, regulatory bodies for use of material for human need, commercial developments and stem cell based products, bio- vigilance, Stem cell regulatory aspects in international and Indian context.

L39- 42: Bench to Bedside using naturally occurring stem cells and induced pluripotent stem cells – Discuss research papers on the advancements in the field

L43- 46: Group discussion on Topics discussed and Paper presentation by students

2 hours for tests.

Books:

1. David Warburton, Stem Cells, Tissue Engineering and Regenerative Medicine, 2015, World Scientific. 2. Sell Stewart, Stem Cell Handbook, 2013, Humana Press. 3. R. Lanza, I. Weissman, J. Thomson, and R. Pedersen, Handbook of Stem Cells, Volume 1-2: 2012, Academic Press. 4. R. Lanza, J. Gearhart et al (Ed), Essential of Stem Cell Biology, 2009, Elsevier Academic press. 5. A. Naggy, N. Habib, M.Y. Levicar, L.G. Jiao and N. Fisk: Stem Cell Repair and Regeneration. Volume-2, 2007, Imperial College Press.

ACBR, CBCS April 2018

6. R. Lanza and I. Klimanskaya, Essential Stem Cells Methods. (2009), Academic Press.

7. Developmental biology by Scott F. Gillbert; Ed.8th; Sinauer Associates; 2006

NEW PAPER: NEW METHODS IN ORGANIC SYNTHESIS Elective Paper: Credits 3

The course aims at understanding the methods by which chemically and biologically important molecules and macromolecules are synthesized and characterized. This course includes an overview of nucleotide synthesis, peptide synthesis alkene metatheis, green chemistry and total synthesis of pharmaceutically beneficial compounds.

Methods in nucleotide synthesis

L1 - Advantage of chemical synthesis L-2- Protecting groups L-3 nucleoside3-phosphoramidates L-4 solid phase synthesis L-5 Oligonucleotide synthesis cycle L-6 Automated oligonucleotide synthesizer L-7 DNA microarrays L-8 Light directed chemical synthesis L-9 Microarray synthesis using micro mirrors L-10 Structure validation

Methods in peptide synthesis L11 solid phase synthesis L12 Protecting groups/deprotection L-13 structure validation

Alkene metathesis

L-14 Mechanism L-15 Metal carbenes L-16 Schrock's catalyst L-17 Grubb's catalyst L-18 Ruthenium catalysts L-19 Ring closing metathesis L-20 Cross metathesis L-21 Polymerization L-22 Ring closing metathesis of small rings L-23 Ring closing metatheis of medium rings L-24 Macrocyclization

Green chemistry

L-25 Introduction L-26 Atom economy L-27 Less Hazardous synthesis L-28 Designing safer chemicals L-29 Design for energy efficiency L-30 Design for degradation L-31-32 Relevant examples L-33-38 Relevant examples of total synthesis

L-38-48 Tutorials/tests/student seminar

ADVANCED IMMUNOLOGY

Semester: III

Elective Paper

Credits: 3+1

Credits: 60 Lectures

Preamble

The course on Advanced Immunology is offered as an Elective paper in the IV semester that builds on the basics taught in the Immunology (MBS204) paper in the II semester. The course begins with a recap on the basics of immunology and immune responses. Emphasis is laid on the recent advances in each aspect of immunology by constant references to peer reviewed papers published in high impact factor journals. Further, eminent scientists working in leading institutes like NII, ICGEB and AIIMS are invited to give lectures on certain topics that have been already covered by teachers.

Course Outcome

At the end of the course the student will have:

1. A detailed knowledge of T cell differentiation, activation and regulation.

2. Appreciated the difference between systemic and mucosal immune responses.

3. The ability to design experiments critically following the experience they have gained via presenting papers in seminars.

4. Knowledge of the nuances of immune responses to various infections and the qualitative and quantum roles of inter-cellular and intracellular molecules.

5. Understanding on the reasons of weaker immunity displayed by aged individuals compared with young individuals to newer and older infections.

1 6. Thus, after finishing the course a student is well trained in all the aspects of immunology and how the body reacts and responds to invading pathogens and other antigenic stimulations.

Detailed Contents

Introduction and Recap of Basic Immunology

L1: Introduction to the Immune system

L2: Adaptive and innate immunity: regulation by Immunoglobulin gene expression, Immunoglobulin loci, TLRs, complement, diversity via gene translocation at Ig loci

L3: Factors regulating immune effector functions

L4: Structure, Function & Antigen processing on MHC class I and MHC class II, factors governing peptide binding, loading and presentation to T cells

L5: Pathogen Interface with Antigen Presentation

T Cell Differentiation, Activation and Functions

L6: Differentiation of T cells: TCR gene recombination, regulation and function therein. Positive and Negative selection of T cells

L7: Factors regulating T cell diversity and cross-reactivity

L8: T cell migration and turnover

L9: Role of costimulatory molecules in T cell selection

L10: T cell functions during various immune responses

L11: Signaling from innate, B cell and T cell receptors: avidity vs affinity of the interactions

L12: T cell response generation and magnitude of the immune response

L13: Heterogeneity in CD4 and CD8 T cell population. CD4 T cell subsets and functions. TH1/TH2/TH9/TH17/Tfh subsets and functions in immunity and disease

2 L14: Hybridoma vs T cell clones vs transgenic vs Knockout mice: applications thereof

L15: Regulatory T cells and fine-tuning of immune response

L16: Solutions and compromises of studying T cells response

L17: T cell memory and short-term and long-term immunity

B Lymphocyte Differentiation, Activation and Functions

L18: Differentiation of B lymphocytes

L19: Activation of B cells by Antigens and modulations by costimulations

L20: Memory B cell responses, turnover and regulation

APC-T Cell Interactions via Costimulation and Immune Synapse

L21: Costimulatory networks in immune response building and maintenance

L22: Positive and negative costimulation by various molecules during building up, maintenance and termination of immune response

L23: Immune synapse and regulation of immune response to pathogens

Mucosal Immunity and Allergy

L24: Introduction to Mucosal immunity vis-à-vis systemic immunity

L25: Intrinsic and extrinsic factors affecting immunity at mucosal surfaces

L26: Exploitation of gaps and weaknesses in the mucosal immunity by pathogens

L27: Mucosal vaccines and diseases

L28: Allergy and hypersensitivity reactions during an immune response

L29: Striking a balance between immunity to infections and allergy

Immunity to pathogens

L30: Immunity to Mycobacteria

3 L31: Immunity to Streptococcus pneumoniae and pneumonia vaccines

L32: Immunity to HIV: Pitfalls of immune-deficiency

L33: Immunity to Salmonella: Current trends and future perspectives

Regulation and Deregulation of Immune Responses

L34: Systemic and organs specific Autoimmunity

L35: microRNAs in regulating immune responses and protozoan immunity

L36: Aging and Immunity and Immune-senescence

L37: Role of Autophagy in mediating immune responses

Transplantation and Tumor Immunology

L38: Transplantation immunology and MHC restriction

L39: Immunity to cancers/tumors vs long-term persistent infections: similarities and differences

Immuno-Therapeutics and Vaccines

L40: Alternative approaches to chemotherapy vis immune-therapeutics and tweaking of the immune system

L41: Vaccines: short-term and long-term protection: inbuilt mechanisms of innate and adaptive memory.

Organogenesis and Lymphoid Development

L42: Organogenesis of secondary lymphoid organs: Overview of the immune system, localization of the lymphoid organs in the body, mouse and human.

L43: The gross anatomy and functional relevance of lymphoid organs.

L44: Review of Timeline based experiments (literature) of development of Peyer’s patches

4 L45: Review of Timeline based experiments(literature) of development of lymph nodes

L46: Literature review of Early and late patterning of lymphoid genes

L47: Lymphotoxin signalling and secondary lymphoid organ development analysis of NALT, MALT, Peyer’s patches and lymphnode.

L48-L60: Seminars/Tests/Discussions