Old Course Curriculum

New Course Curriculum

Semester I

Following courses will run in Sem I

Text ReferenceV. Texts/ References C.R. Cantor & P.R. Schimmel; Biophysical Chemistry, Part-2. W.H.Freeman & Co. 1980. J.R. Lalcowicz; Principles of Fluorescence Spectroscopy. Plenum Press. J.D. Campbell & RA. Dwek; Biological Spectroscopv. Benjamin, 1984. P.S.C Mathews; Quantum Chemistry of Atoms and Molecules. Cambridge University Press, 1986.
DescriptionElectromagnetic and quantum theory of radiation; Wave-particle duality; Photons; Interaction of light with matter, Transition dipole moment; Jablonsky diagram; UV-visible absorption spectroscopy: Beer-Lambert`s law; applications of UV-visible difference Spectroscopy; Circular dichroism in protein analysis: Fluorescence spectroscopy of Biomolecules: quantum yield, static and dynamic quenching of fluorescence, energy transfer, polarization, anisotropy, time-resolved fluorescence; Vibrational Spectroscopy: IR, FT-IR and Raman spectroscopy of biomolecules. Nuclear Magnetic Resonance Spectroscopy: chemical shifts, coupling constants, ring currents, paramagnetic shifts, spin-spin and spin-lattice relaxation times, NOE, chemical exchange, applications application to biomolecular structure and dynamics; Mass spectrometry of biomolecules; X-ray diffraction: Crystal systems and space groups, Miller indices and space lattices, Diffraction of x-rays and Braggs law, Electron Microscopy of Biomolecules and fluorescence microscopy.
Text ReferenceRobert F. Weaver, Molecular Biology 3rd Edition, McGraw-Hill, 2003. Benjamin Lewin, Genes IX. Jones and Bartlett Publishers, 2007.
DescriptionNucleic acids, DNA structure, central dogma; Replication: eukaryotic and prokaryotic replication, mechanism and control, replication of double stranded and single stranded circular DNA, the end-replication problem and telomerase; Nucleosomes: eukaryotic and prokaryotic genome packing, heterochromatin, euchromatin; Transcription: mechanism of RNA transcription in prokaryotes and eukaryotes; model systems of transcriptional control: lac operon, lambda phage; promoters, enhancers, repressors; RNA processing: processing of heterogeneous nuclear RNA: splicing, capping, polyadenylation; Translation: universal genetic code, degeneracy of codons, mechanisms of initiation, elongation and termination of translation, wobble hypothesis, genetic code in mitochondria; Mutations: nonsense, missense, frameshift and point mutations; intragenic and intergenic suppression; DNA repair: photoreactivation, excision, mismatch and SOS repair; Recombination: mechanism of homologous recombination in prokaryotes, site specific recombination, insertion sequences, transposons.
Text ReferenceD. Holme & H. Peck; Analytical Biochemistry. Longman, 1983. T.G. Cooper; The Tools of Biochemistry. Wiley Intersciences, 1977. R. Scopes; Protein Purification – Principles & Practices. Springer Verlag, 1982. Selected readings from Methods in Enzymology, Acadernic Press. R.C.Price, Proteins. Lafbax Academic Press 1996. Skoog et al., Fundamentals of analytical chemistry. 7th edition. Harcourt College Publisher, 2001.
DescriptionSeparation techniques in biochemistry: Centrifugation, TLC and Paper chromatography, gel permeation, ion exchange, hydrophobic, reverse-phase and affinity chromatography, HPLC and FPLC, Electrophoretic techniques, Criteria of protein purity, equilibrium dialysis, ultrafiltration and various membrane techniques, API-electrospray and MALDI-TOF, Mass spectrometery Radiotracer techniques for enzyme assays, receptor-ligand interactions; radioimmunoassay, ELISA
Text ReferenceBiothermodynamics : the study of biochemical processes at equilibrium, Edsall, J.T., Gutfreund, H., Chichester : John Wiley, 1983 Biological thermodynamics, Haynie, D.T. Cambridge: Cambridge University Press, 2001 Thermodynamics and kinetics for the biological sciences Hammes, G.G. J Wiley 2000 Atkin’s Physical chemistry. 8th ed. P W Atkins & J. dePaula, Oxford Univ Press, 2008
DescriptionThermodynamic functions – U, A, H, S and G. The First law: work, heat, energy, heat transactions, enthalpy, standard enthalpy changes. The Second law: entropy, entropy changes accompanying specific processes; The Third law and Biology. Chemical equilibrium: Gibb’s energy minimum, description of equilibrium, How equilibria respond to pressure, temperature & pH. Applications of thermodynamic principles to biological systems. Statistical thermodynamics: distribution of molecular states (introduce molecular partition function), the internal & the statistical entropy, Boltzmann distribution. Basic kinetic concepts: Reaction stoichiometry, rates of consumption & formation, extent of reaction, rate of reaction, Analysis of kinetic results, influence of temperature on reaction rates. Theories of reaction rates: Kinetic theory of collision, transition state theory of reaction rates, potential energy surfaces and reaction dynamics; diffusion; kinetics of unimolecular and bimolecular reactions; application of kinetics to biological systems. Catalysis: General catalytic mechanism (Arrhenius intermediate, Van’t Hoff intermediate), Acid-base catalysis, acidity function, Enzyme catalysis, Michealis-Menten equation, Inhibition, effects of pH, Bisubstrate reactions (sequential reaction, ping-pong reactions).
Text ReferenceMathematics for Biological Scientists, M. Aitken, B. Broadhursts, S. Haldky, Garland Science (2009) Introduction to Mathematics for Life Scientists, E. Batschelet, Springer Verlag, 3rd edition (2003) Calculus for Life Sciences, R. De Sapio, W. H. Freeman and Co. (1976) Physical Biology of the Cell, R Phillips, J Kondev, J. Theriot, Garland Science (2009) Random Walks in Biology, H. C. Berg, Princeton university press (1993)
DescriptionCalculus: Idea of functions using examples from biology (e.g., Concentrations of proteins as a function of space and time. Circadian oscillations) Differentiation. Plotting functions. Integration. Calculus of growth and decay processes. Differential equations. Vectors, Co-ordinate systems: Scalars and vectors. Spherical polar coordinates, Cylindrical coordinates. Use of these coordinate systems (e.g., 3-dimensional configuration of proteins ) Probability and Statistics: Relevance of stochasticity in biology. Need of using statistical methods. Mean, variance, standard deviation, Errors, fitting a function to an experimental data set — linear and non-linear fits. Introduction to probability, Probability distributions, Moments, Binomial distribution , Normal distribution , Poisson distribution, Examples from biology.(e.g., Knudson’s two-hit hypothesis, Luria-Delbruck fluctuation test, Wright-Fisher model) Fourier transformation and its application in biology (e.g., crystallography, optics)
Text ReferenceC.G. Cooper; Tools of Biochemistry, Wiley Interscience, 1977. E.D. Holme & H. Peck; Analytical Biochemistry, Longman, 1983. R. Scopes; Protein Purification – Principles and Practices, Springer Verlag, 1982
DescriptionTheory: Buffers & pKa; Cell fractionation; Estimation of Protein, Nucleic Acids, Lipid, Carbohydrate; Enzyme purification, purification table, definition of units- Km and Vmax determination, Criteria of purity; electrophoresis methods; Immunochemical methods of analysis. Experiments: Buffer preparation: finding out buffering zone and pKa value; Protein estimation by Lowry, Bradford, UV-visible method; Sugar estimation; Thin layer chromatography; Electrophoresis technique: Agarose and SDS-PAGE; Preparation of cell free extract, detection of enzyme activity and calculation of specific activity; Column chromatographic techniques: ion-exchange and gel-filtration chromatography

Semester II

Following courses will run in Sem II

Text Reference
  • Biophysical Chemistry, Vol. 1 & 3. C.R.Cantor and P.R.Schimmel; W.H. Freeman, 1980.
  • Structure and Molecular properties. T.Creighton. W.H.Freeman, 2nd ed. 1992.
  • Protein structure. A practical approach. T.Creighton. Oxford Univ. Press. 2nd ed. 1997.
  • The structure of biological membranes. P.L.Yeagle. CRC Press. 2nd ed. 2004.
Description

Molecular structure; Torsion angles; Steric effect: Contact distances; Homomorphous sugars; cis & trans peptide bonds; Ramachandran map: for amino acids and as a general conformational analysis tool. Non-covalent interactions; hydrogen bond; stacking; Entropy: Entropy/enthalpy compensation; A=T vs. G≡C. Effective conc. Enthalpic and entropic co-operativity. Oligopeptide conformation. Conformationally constrained amino acids; Hydrophobic effect; Affinity and specificity in intermolecular interactions; Stability of protein structure; Folding / unfolding; m values; Models of protein folding; Folding funnel; Contact order; F value analysis; Denatured state; Intrinsically unfolded proteins; Protein and RNA folding; In vivo folding; Kinetically stable proteins; Lipids: Assemblies; Volume, surface area, length relationship; X-ray studies; Phase transitions of anhydrous and hydrated lipid bilayers.

Text ReferenceProgramming Python, M Lutz, O302222Reilly Media, 4th edition (2011)Learning Perl, R.L. Schwartz, B.D.Foy, T.Phoenix, O302222Reilly Media, 6th edition (2011).The C++ programming language, B.Stroustrup, Addison-Wesley Publishers, 4th edition (2013)
DescriptionAny one of the programming languages Perl, C++ or python. Introductory concepts (higher level programming, assembly level coding, compilers, libraries, STDIN, STDOUT); Variable types, declarations, scalars, arrays, etc. Operators (assignment, etc.), Control structures and conditional statements; loops (do, while, until, etc.), subroutines. Illustrative problem solving with applications in Bioinformatics.
Text ReferenceProgramming Python, M Lutz, O302222Reilly Media, 4th edition (2011)Learning Perl, R.L. Schwartz, B.D.Foy, T.Phoenix, O302222Reilly Media, 6th edition (2011).The C++ programming language, B.Stroustrup, Addison-Wesley Publishers, 4th edition (2013)
DescriptionAny one of the programming languages Perl, C++ or python. Introductory concepts (higher level programming, assembly level coding, compilers, libraries, STDIN, STDOUT); Variable types, declarations, scalars, arrays, etc. Operators (assignment, etc.), Control structures and conditional statements; loops (do, while, until, etc.), subroutines. Illustrative problem solving with applications in Bioinformatics.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. R.S. Ochs, R.W. Hanson and J. Halls; Metabolic Regulation. Elsevier, 1985. 2. P.W. Atkins; Physical Chemistry. ELBS, 1981. 3. J.G. Morris; A Biologist`s Physical Chemistry. 1974. 4. Lehninger Principles of Biochemistry. D.L.Nelson and M.M.Cox. 4th ed. W.H.Freeman, 2004. 5. Cellular physiology of nerves and muscles. G.G.Mathews. 4th ed. Blackwell Publishers, 2003. 6. Bioenergetics. D.G.Nicholls and S.J.Ferguson, 2nd ed. Academic Press, 2002.
DescriptionOverview of metabolism; concept of flow of matter and energy; thermodynamics of coupled systems and non-equilibrium reactions; biological energy currencies: high energy bond, reducing power and inter conversions of energy forms; carbon, nitrogen cycles in biosphere; classification of living system based on carbon and energy requirements; methods to study metabolism; carbohydrate and lipid catabolism; glycolysis; TCA cycle; fatty acid oxidation, other metabolic routes of carbon; oxidative phosphorylation; biosynthesis of carbohydrates and lipids photosynthesis; photosynthetic electron transport; Calvin cycle and other avenues of harvesting light energy; gluconeogenesis; Cori cycle; glycogen metabolism; biogenesis of fatty acids and sterols; nitrogen metabolism: sources of organic nitrogen; flow of nitrogen into biosynthesis and catabolism of amino acids; central role of glutamine; purines and pyrimidines; the metabolism of nucleotides; urea cycle and excretion of nitrogen; integration of metabolism and concepts of metabolic regulation.
Text Reference
  • R. Cantor and P.R. Schimmel; Biophysical Chemistry (Vol. 2-3). W.H. Freeman, 1980. T.E. Creighton; Protein Structure. I.R.E. Press, 1989.
  • R. ; Principles of Fluorescence Spectroscopy. Plenum Press, 1983. Methods in Enzymology Series. Academic.
Description

Theory: Reaction kinetics, rate laws, temperature dependence on rate constants, applications of kinetics to biological systems, DNA melting and renaturation, protein unfolding and folding, ligand binding to macromolecules, ligand induced conformational changes, protein-protein interaction.
Experiments: Use of UV-Vis spectroscopy and fluorescence spectroscopy to determine solvent exposure/accessibility of aromatic amino acids, in measurement of thermodynamic parameters of heat denaturation of proteins and nucleic acids, in measurement of the conformational stability of a protein; estimation of secondary structure of proteins by CD; determining the binding constant as the number of binding sites by Scatchard plot.; EPR and the use of spin labels; proton NMR of amino acids; assigning the proton resonances of peptides by NMR; FT-IR of protein; electrospray ionization mass spectroscopy; determination of molecular weight of a protein; modeling biomolecule and biomolecular processes by computer simulations and graphics.

Text Reference
  • Programming Python by M.Lutz, O’Reilly media, 2011, 4th
  • Learning Perl by R.L.Schwartz, B.D.Foy, T.Phoenix, O’Reilly meida, 2011, 6th
  • The C++ programming language, by B.Stroustrup, Addison-Wesley professional publishers, 2013, 4th edition
Description

Any one of the programming languages Perl, C++ or python. Introductory concepts (higher level programming, assembly level coding, compilers, libraries, STDIN, STDOUT); Variable types, declarations, scalars, arrays, etc. Operators (assignment, etc.), Control structures and conditional statements; loops (do, while, until, etc.), subroutines. Illustrative problem solving with applications in Bioinformatics.

Semester III

Following courses will run in Sem III

Text Reference
  • Enzymatic reaction mechanisms by C. Walsh. WH Freeman, San Francisco, 1979.
  • Enzyme Kinetics by I. Segel. Wiley Interscience, NewYork, 1993.
  • An introduction to enzyme and coenzyme chemistry by T. Bugg 2nd Ed., Blackwell Publishers, Oxford, 2004.
  • Enzyme Kinetics: Principles and Methods by H. Bisswanger Translated by L. Bubenheim.
  • Wiley-VCH Verlag GmbH, Weinheim, Germany, 2002.
  • Fundamentals of Enzyme Kinetics by A. Cornish-Bowden 3rd Edition, Portland Press, London, 2004.
Description

Rate accelerations in biological systems; Catalysis and historical perspective on enzymes; Overview of applied enzymology and enzyme technology; Enzyme nomenclature; Origins of enzyme catalytic power; Structural basis of enzyme action and characterization of active site residues; Kinetic approaches to understand enzyme action; Michaelis-Menten kinetics; Evaluation of Km, kcat and enzyme inhibition analysis; Concept of an efficient catalyst; Elucidation of kinetic mechanism through initial velocity, product inhibition, pH and isotopic analysis; Role of metal ions in enzyme catalysis; Integration of kinetic, chemical and structural data to describe enzyme action; Control of enzyme activity and its role in regulating metabolism – in vivo enzymology; Frontiers in enzymology: Rational design of an enzyme catalyst, directed evolution, abzymes, non-protein catalysts.

Text Reference
  • Old & Primrose; Principles of Gene Manipulation. S.B.University Press, 6th edition, 2001.
  • Maniatis, E.F. Fritsch & J. Sambrook; Molecular Cloning: A Laboratory Manual. CSHL, 3rd edition, 2002.
  • A. Innis, D.H. Gelfand, J.J. Sninsky & T.J. White. PCR Protocols. Academic Press, 1990.
Description

Concept of recombinant DNA technology and purpose, basic methodology, use of plasmids, Type I, II and III restriction modification systems, type II restriction endonucleases, nomenclature and sequence recognition, mcr and rnrr genotypes, linkers, adaptors, blunt end ligation, homopolymeric tailing, Transformation, methods in screening recombinant DNA. Radioactive and non-radioactive methods for labeling DNA: Nick translation, random priming, use of Klenow enzyme, T4 DNA polymerase, bacterial alkaline phosphatase, polynucleotide kinase, hybridization techniques, northern, Southern and colony hybridization. Restriction maps and mapping techniques. PCR technology, enzymes in PCR, hot-start, touchdown PCR, primer design, introduction of restriction sites etc. Construction of cDNA libraries in plasmids, hybrid select translation, RT-PCR and quantitative RT-PCR. Strategies for maximizing gene expression, prokaryote expression vectors; pMal, GST fusion vectors, pET vectors and their applications in expression, quantitation, purification. Inclusion bodies, approaches to solubilization, Intein based expression and purification vectors. Cloning in M13 mp vectors, application to DNA sequencing, site-directed mutagenesis; PCR-based mutations. Transcription vectors. Lambda vectors; insertion and replacement vectors, selection and screening recombinant phage, in vitro packaging, genomic libraries and cDNA cloning, application of lgt10, lgt11, lZAP vectors. Cosmid vectors. Yeast transformation, yeast cloning vectors, specialized vectors such as gap and retrievers, principles and application of dihybrid systems. Cloning and expression in mammalian cells, methods of selection and screening, application of reporter genes. Basic principles of transcriptomics and proteomics.

Text Reference
  • Janos Kuby; Immunology 2nd edition. H. Freeman and Company New York, 1994.
  • E. Paul; Fundamental Immunology. Raven Press, 1998.
  • Immunobiology: the immune system in health and disease. 5th ed. C A Janeway et al., Garland Publishing company, 2001.
  • Cellular and Molecular Immunology. 4th ed. A K Abbas, A. H Lichtman, J S Pober, W B Saunders Company, 2000.
Description

Natural immunity, defensins, pathogen associated recognition motifs, Toll receptors, complement system, applications of complement proteins in rapid clearance of pathogens, acquired immunity: immune cells, antigens haptens, B and T cell epitopes, antibodies: structure and function, monoclonal antibodies, single chain antibodies, domain antibodies, antigen antibody reactions, genetics of immunoglobulins and antibody diversity, Major Histocompatibility Complex, structure and functions of class I and class II MHC molecules, antigen presentation by MHC and non MHC molecules, cytokines, in vivo regulation of immune responses, B and T cell activations, hypersensitivity, mucosal immunity, introduction to transplantation immunology tolerance, tumor immunology and vaccines.

Text Reference
  • T Maniatis, EF Fritsch, J Sambrook; Molecular cloning. A laboratory manual. 3rd edition. Cold spring harbor laboratory press, 2001.
  • C Hardin, J Edwards, A Riell, D Presutti, W Miller and D Robertson; Cloning, Gene Expression and Protein ; Experimental procedures and process rationale. Oxford University Press, 2001.
Description

Theory: The emphasis of the lab is on understanding the principles behind experiments, the ability to design and execute experiments and time management. The purpose of various steps and project planning will be discussed.
Experiments: (1) Isolate genomic DNA from Bacillus subtilis (or equivalent organism) genome, (2) PCR amplification of scoC gene and analysis by agarose gel electrophoresis. (3) Preparation of plasmid pET-28a from E. coli DH5α and gel analysis. (4) Restriction digestion of vector (gel analysis) and insert with NcoI and XhoI (5) a. Vector and insert ligation, b. Transformation in E. coli DH5α. (6) Plasmid isolation and confirming recombinant by PCR and RE digestion. (7) Transformation of recombinant plasmid in BL21(DE3). (8) Induction of ScoC protein with IPTG and analysis on SDS-PAGE. (9) Purification of protein on Ni-NTA column and analysis of purification by SDS-PAGE. (10) Random primer labeling of scoC with Dig-11-dUTP (12) Southern hybridization of B. subtilis genome with probe and non-radioactive detection.

Text Reference
  • Keith, J. Humana Press, 2008.
  • Computer methods for macromolecular sequence analysis. R.F.Doolittle, Academic Press, 1996.
  • Sequence and genome analysis. D.W.Mount. Cold Spring Harbor Lab. press. 2004.
  • Bioinformatics and functional genomics. J. Pevsner. Wiley-Liss, 2003.
  • Encyclopedia of Genetics, Genomics, Proteomics & Bioinformatics, Jorde et al., (eds.) John Wiley and Sons, 2005.
Description

Introduction; Databases – sequence, structure, non-redundant; Sequence alignment – pairwise and multiple; phylogenetics; ORFinder; Structure prediction methods – high-accuracy, template based, free modeling (new folds); Secondary structure prediction; Pattern recognition – PSSMs, weight matrices; hidden Markov models

Electives Listed Below

Project Stage I

Elective I

Elective I courses

Text ReferenceAn introduction to genetic analysis, Griffith et al W.H. Freeman and Company, 10th edition (2011).Human molecular genetics, Strachan and Read, Taylor and Francis, 4th edition (2010).Principles of Genetics, Snustad and Simmons, John Wiley and Sons, 6th Edition (2011).
DescriptionMendelian genetics; deviation from Mendelian ratiosCrossing over and Linkage analysis; Fine structure analysis of a gene; Concept of mutation; Complementation analysis; Recombination; Cytoplasmic inheritance; Sex-linked inheritance; Transposons; Chromosomal aberrations (structural and numerical) and associated diseases; population and evolutionary genetics.

 

Text ReferenceMultilayer Thin Films, G Decher, JB. Schlenoff, Wiley-VCH Verlag GmbH & Co. KGaA (2003)Bionanotechnology, Lessons from Nature; D S. Goodsell, Wiley-Liss (2004) Biomedical Nanotechnology, N H. Malsch, CRC Press (2005)Nanotechnologies for the Life Sciences, Vol 2, Biological and pharmaceutical nanomaterials; Challa Kumar, Wiley-VCH, (2006)
DescriptionIntroduction to Bio-Nanotechnology, Cellular nanostructures, self-assembly of colloidal nanostructures of biological relevance, biofunctional nanoparticles, Nanoparticles for drug delivery (including solid lipid nanoparticles, synthetic and biopolymeric nanoparticles), carbon nanotubes, polymeric nanofibers, quantum dots, magnetic nanoparticles and gold nanostructures for theranostics, Multilayer Thin Film: Polyelectrolyte multilayers, coated colloids, smart capsules, Nanoengineered biosensors, Nanotechnology for Biodefense, Implants and Prosthesis, Implications in neuroscience, tissue engineering and cancer therapy, and Environmental and safety aspects of bio-nanotechnology.

 

Semester IV

Elective II and Elective III

Seminar

Project Stage II

Elective II & III

Elective II and III courses

Text ReferenceHistorical Introduction to the Philosophy of Science, J Losee, Oxford University Press (1972). Philosophy of Biology, Ruse Michael (ed), MacMillan (1989) Scientific method in Practice, Gauch H G. Jr., Cambridge University Press (2003). Selected readings from Reviews and Commentaries.
DescriptionIntroduction to philosophizing: language, truth and logic. A review of history of philosophy of science. Scientific imagination; case studies of Mendel and Galileo. The scientific methods in the practice of biology. The success of reductionist approach to problems in molecular biology. Contrast with holistic (higher level) biology. Resurgence of interest in global approaches like- systems biology, complexity and various “Omics”. Richness of biology in cyclical phenomena with interdependent parallel processes, feedback loops and networks. Emergent properties of the system. The concept of Causality in light of extant complexity. Complexity and indeterminacy in Biology. Historical contingency and evolution. History, nature and the future of Biology: Physics-biology interface during the classical period; biology as an independent science during the 19th and 20th centuries (the major concepts and their evolution); the nature of explanation in modern biology; the future directions. The interface between Biology (Genetics) and Society: some controversies. Darwinism, Lamarckism and Creationism; Eugenics, its history and future; ELSIfication of biology. Genetic screening; Evolution of ethics and ethics in post-genomic society. Bio-safety and environmental concerns. Molecular organizing principles of living systems. Ontogenic theories based on molecular self-organization. Importance of template replication and macromolecular catalysis. Protein first or DNA first conundrum. RNA world hypothesis. Present consensus and remaining challenges.
Text ReferenceJ.G. Nicholls, A.R. Martin & B. Wallace: From Neuron to Brain, 3rd ed., Sinauer, Sunderland, 1992. R.D. Barr & R.L. Plonsey: Bioelectricity: A Quantitative Approach, Academic Press, N.Y., 1988. E.R. Kandel & J. Shwartz (ed.): Principles of Neural Science, 3rd ed., 1991.
DescriptionAction potential of excitable cells: Quantitative description, Hodgkin-Huxley model, significance of parameters in Hodgkin-Huxley equations; Voltageclamp experiments: design, and analysis of results; Factors determining the initiation, amplitudes, and kinetic properties of action potentials. Passive membrane electrical properties: Cellular resistance, capacitance, time constant and space constant, methods of measurement; Importance in cellular excitation and signaling: Impulse propagation. Electrophysiology of synaptic transmission: Prejunctional and postjunctional electrical events; time courses of transmitter-activated membrane currents and potentials in skeletal and smooth muscle; Electrical models of the skeletal and smooth muscle membranes
Text ReferenceSince this course will be research-oriented, there is, if no official textbook other than original research necessary) papers and reviews identified by the instructor. Students will be responsible for downloading and printing PDFs. B. Alberts, D. Bray, J. Levis, M. Raff, K. Roberts & J. D. Watson: Molecular Biology of the Cell; 5th Ed, Garland Science Fung, Y. C.: Biomechanics: Mechanical Properties of Living Tissues. 2nd Ed., Springer.R. Kamm and M. K. Mofrad. Cytoskeletal Mechanics: Models and Measurements. Cambridge University Press.
DescriptionMechanical forces are known to play an increasinglyimportant role during development, normal functionas well as in disease. This course will focus on thephysical interactions between cells and theirsurroundings. Students will learn how cells sense andrespond to external forces and cues, and how thesemechanical inputs influence subcellular biochemistryand cell behavior. They will also study variousexperimental techniques that have been developed forprobing cell structure, manipulating cells andmeasuring their mechanical properties.
Text Reference1. Blitterswijk CV, Tissue Engineering, Academic Press (2008).2. Saltzman WM, Tissue Engineering, Oxford University Press (2004).3. Lanza RP, Langer R, Vacanti JP, Principles of Tissue Engineering, Academic Press, 3rd Edition (2007). 4. Palsson B and Bhatia SN, Tissue Engineering, Pearson Prentice Hall (2003).
DescriptionBasic cell biology, cell-matrix interactions, receptor biology, cell culture, gene therapy and gene transfer techniques, protein and peptide engineering, stem cell programming, controlled release and drug delivery, tissue ablation, engineering angiogenesis, vascularization, material based immuntherapy and case studies involving skin, bone, liver, muscle tissue engineering.
Text ReferenceMartin Bland: An Introduction to Medical Statistics, Oxford University Press, 1995. Wayne Daniel: Biostatistics: Foundation for Analysis in the Health Sciences, 5th ed., John Wiley & Sons, New York, 2009. 9th Edition Marcello Pagano, Principles of Biostatistics, Cengage Learning India, 2000, 2nd Edition P. G. Hoel, S. C. Port, and C. J. Stone, Introduction to Statistical Theory, Universal Book Stall, New Delhi, 1994
DescriptionAnalytics in biology and medicine. Probability, statistics and stochastics. Applications in biology and medicine will be given at each topic below. A. Descriptive statistics, quantitative parameters and inferential statistics. B. Events and samples spaces, algebra of events, Venn diagram, random events, axiomatic definition of probability, probability as relative frequency. Independence, mutually exclusive events, conditional events, Bayes’ rule and theorem, counting-permutation-combination and probability, application to diagnostics, types of errors, evaluation of odds and risks. C. Random variables as functions, discrete and continuous random variables, probability mass function, common discrete distributions – Bernouli, Binomial, Geometric, Poisson, z-transform, marginal and joint distributions, applications D. Continuous random variables and distributions, Normal, exponential and gamma, Chi Square, t, and F distributions, characteristic/moment-generating functions E. Estimation of mean and variance and their distributions, Central Limit Theorem and sample size, confidence intervals, applications F. Testing for single or two populations for the mean with and without knowledge of variance, Normal and Student `t’ test, Chi Square/F test for the variance of one/two populations, G. G. Independence of attributes and Chi Square test for goodness of fit. H. Experimental design: randomization, factorial, Latin square, and sequential cross-over design, F Test and Applications. I. Non-parametric and distribution-free statistics, some important nonparametric tests; sign test, Wilcoxon`s rank test and Spearman`s rank, correlation. J. Classification (differential diagnosis), sequential clinical trials, and other applications. K. Introduction to regression and time-series, data mining for patterns, analytics. L. Laboratory sessions for descriptive statistics, testing and experimental design, using open source software R
Text Reference* A. W. Norman and G. Litwack; Hormones. Academic Press, 1987. * G. G. Gilman, L. S. Goodman, T. W. Rall and F. C. Murad (Eds.); The Pharmacological Basis of Therapeutics (7th ed). Macmillan, 1985. * G. Posli and S. T. Crooke (Eds.); Mechanisms of Receptor Regulation. Plenum Press, 1985.
DescriptionOver view of cell-cell and intracellular signaling mechanisms, endocrine, paracrine, autocrine and synaptic transmissions. Cell-cell recognition, cell-adhesion molecules. Receptors (extracellular, intracellular), receptor-ligand interactions (agonist and antagonist), receptor characterizations, receptor functions. Extracellular receptors: coupling of receptors to different signal transducing machinery; G-poteins, ion channels, and catalytic proteins. G-proteins: structure, function, adenylate cyclase system, cAMP-PK and CREB proteins. Calcium channels, oscillations of calcium conc. as signals. Receptors with protein tyrosine kinase activity, structure and function. Intracellular receptors: steroid receptors, structure and function. Second messengers; phosphoinositides, inositol 1,4,5 tris phosphate, diacyl glycerol, cAMP, cGMP, arachidonic acid, prostaglandins, NO. Mechanisms of signal transduction: coupling of activation of receptors to intracellular signal transducing machinery, protein kinase cascades, gene regulation. Regulation of receptor function; receptor modifications, adaptation of cells. Signal transduction pathways in development and disease. Relationship of receptor tyrosine kinases with proto-oncogenes. Developmental abnormalities due to defective signalling pathways. Signal transducing machinery as targets for potential drugs 
Text Reference* Crueger and A. Crueger; Biotechnology: A Textbook of Industrial Microbiology (Eng. Ed. T. D. Brook). Sinaeur Associates, 1990. * L. E. Casida, Jr.; Industrial Microbiology. Wiley Eastern Ltd., 1989. * G. Reed (Ed.); Prescott and Dunn`s Industrial Microbiology (4th Ed.). CBS Publishers, 1987. * H. J. Rehm, G. Reed and H. Pape (Eds.) Biotechnology (A Comprehensive Treatise vols. 1-8). VCH, 1986. * Harry W.Seeley,Jr. and Paul Van Denmark; Microbes in Actions: A lab Manual of Microbiology. D. B. Taraporwalla and Sons, 1984.
DescriptionThe scope of industrial microbiology. Screening strategies for new metabolite such as antibodies, enzymes, amino acids and other substances. Strain improvement methods and their application. Fermentation media, stock cultures, and inoculum preparation. So urces of raw materials for Biotechnology industry. Fermentation procedures, purification and recovery of products. Biochemical basis of production processes. Production, structure, biosynthesis, regulation and uses of organic acids, amino acids, nucleosid es, nucleotides and related compounds, vitamins antibiotics and ergot alkaloids. Microbial transformations and their application. Immobilised enzymes and cells. Enzymes as products of fermentation. Representative examples – Penicillin acylase, glucose iso merase, invertase. Aspects of single cell proteins, microbial leaching, Extra cellular polysaccharides. A brief introduction to patents and secret processes. Fermentation economics and process appraisal.
Text Reference# H. J. Rehm, G. Reed and H. Pape (Eds.); Biotechnology: A Comprehensive Treatise in eight volumes. VCH, 1986.# M. Moo-Young (Eds.); Comprehensive Biotechnology (3 Vols.). Elsevier, London 1986.# Selected reviews and articles from Nature, Science, Annual reviews etc.
DescriptionThis course covers three to four contemporary themes in Biotechnology from among: Plant cell culture and tissue culture; Enzymes and Biocatalyses- immobilized enzyme applications; Bioconversion/fermentation of industrial fine chemicals; Antibiotics and chemotherapy; Recombinant DNA technology and protein therapeutics; Waste treatment, Utilization and methanogenesis.
Text ReferenceStrickberger`s Evolution. Brian K. Hall & BendiktHallgrimsson, Jones and Bartlett Publishers, 4thedition, 2007.Evolution. Nicholas H. Barton, Derek E. G. Briggs, Jonathan A. Elison, and Nipam H. Patel. ColdSpring Harbor Laboratory Press, 2007.Sequence – Evolution 302226 Function: ComputationalApproaches in Comparative Genomics. Eugene VKoonin and Michael Y Galperin. NCBI, NLM,NIH, Boston: Kluwer Academic, 2003.On the origin of species. Charles Darwin, 1859.Recent research articles, reviews, news, and views
DescriptionIntroduction, historical perspectives: pre-Darwinian, Darwinian and Neo-Darwinian theoriesofevolution, cosmic origins of earth, pre-biotic earth,from molecules to life, RNA world & transition toDNA world, evolution of genetic code, origins ofcell and first organisms, fossils and evolution, LastUniversal Common Ancestor (LUCA), tree of life,viruses and orphan replicons, endosymbiosis,evolution of eukaryotes, origin of species, naturalselection, Mendelian genetics, chromosomesegregation and sex determination, geneticvariation, regulation and mutation, populations,genefrequencies and Hardy-Weinberg equilibrium,species and speciation, phylogeny andclassification,diversity of life: evolution of plants and animals,human origins, viral evolution: influenza & HIV,functional genomics, horizontal gene transfer,introduction to game theory, unsolved mysteries ofevolution.
Text Reference1.302223Biomolecular Crystallography: Principles, Practice, and Application to Structural Biology302224 by Bernhard Rupp: Garland Science, Taylor & Francis Group LLC., 1st edition, 2010.2.302223Crystallography Made Crystal Clear: A Guide for Users of Macromolecular Models302224 by Gale Rhodes: Elsevier Inc., 3rd edition, 2006.3.302223Principles of Protein X-Ray Crystallography302224 by Jan Drenth: Springer Science + Business Media LLC., 3rd edition, 2007.
DescriptionIntroduction about the course, Brief introduction about protein structure, Protein production for crystallization, Protein crystallization, Crystal geometry, X-ray diffraction, Statistics and probability in crystallography, Instrumentation and diffraction data collection, Diffraction data to electron density, Solving phase problem, Isomorphous replacement method, Anomalous scattering method, Phase combination and improvement, Molecular replacement, Model building and refinement, Structure validation and deposition, Judging a crystallographic model, Computer program for analyzing protein structures, Tutorials, Structure analysis.
Text ReferenceJohn G. Webster (ed.): Medical Instrumentation – Application and Design; Houghton Mifflin Co., Boston, 1992.Richard Aston: Principles of Biomedical Instrumentation and Measurement, Merril Publishing Co., Columbus, 1990.Richard S.C. Cobbold : Transducers for Biomedical Measurements: Principles and Applications, John Wiley & Sons, 1974Ernest O. Doeblin: Measurement Systems, Application and Design, McGraw-Hill, 1985A.P.F. Turner, I. Karube & G.S. Wilson: Biosensors : Fundamentals & Applications, Oxford University Press, Oxford, 1987.
DescriptionSensor architecture and Classification; Medically significant measurands, functional specifications of medical sensors; Sensor characteristics : linearity, repeatability, hysteresis, drift; Sensor models in the time & frequency domains.Sensors for physical measurands: strain, force, pressure, acceleration, flow, volume, temperature and biopotentials.Sensors for measurement of chemicals: potentiometric sensors, ion selective electrodes, ISFETS; Amperometric sensors, Clark Electrode; Biosensors, Catalytic biosensors, immunosensors.
Text ReferenceA. Burger, Medicinal Chemistry, 4th Ed., Wiley Interscience, 1981. R.F.Doerge, Ed., Wilson and Gisveld”s Text Book of Organic Medicinal and Pharmaceutical chemistry, 8th Ed., J.B. Lippincott Co., 1982. D. Lednicer and L.A. Mitscher, The Organic Chemistry of Drug Synthesis, Wiley Interscience, 1977. O.L.Salerini, Natural and Synthetic Organic Medicinal Compounds, C.V. Mosby Co., 1976.
DescriptionA brief history of medicinal chemistry. Drug receptor interactions. Approaches to drug design. Drug metabolism. A few drugs from each of the following groups will be discussed. Analgesics, antidepressants, antipsdychotics, antiinflammatory agents, cardiovascular agents, diuretics, antibacterials, antibiotics, antivirals, antimalarials, antiamoebics, drugs for neoplastic deseases. Vitamins : A, B1,B2, B6 niacin, folic acid, dantothenic acid, biotin, B12,C,D,E,and K. Hormones : Thyroid hormones and antithyroid drugs. Steroid hormones and some important steroidal drugs.
Text ReferenceNielsen, J. and Villadsen, J., Bioreaction Engineering Principles, Plenum Press, New York, 1994. Stephenapoulous, G, Aristidou, A and Nielsen, J., Metabolic Engineering: Principles and Applications, Academic Press, New York, 1999. Schugerl, K. and Bellgardt, K. V., Bioreaction Engineering: Modeling and Control, Springer Verlag, Heidelberg, 2000.
DescriptionStructured growth models; compartmental models, cybernetic and optimal models, stoichiometric models, immobilized enzyme kinetics, multi-enzyme kinetics. Reactor design, use of structured models, bubble column reactors, fed-batch operation, immobilized cell reactors, immobilized cell reactor/separator, simultaneous enzyme and cell reactors. Metabolic Engineering, Flux analysis, Biochemical Systems Theory (BST), Metabolic Control Analysis (MCA), Genetic models, Protein production kinetics, Analysis of genetic switches.
Text ReferenceBaker, K H., and Herson, D. S., Bioremediation, McGraw-Hill Publishing Company, New York, 1994 . Eweis, J. B., Ergas, S. J., Chang D. P. Y., and Schroeder E. D., Bioremediation Principles, McGraw-Hill Publishing Company, Singapore, 1998.
DescriptionCurrent bioremediation practice and applications; Microbial systems of bioremediation; Factors influencing bioremediation (environmental factors, physical factors and chemical factors); Genetic responses of microorganisms to the presence of pollutants (plasmid coded inducible degradative enzymes); Application of genetically engineered microorganisms for hazardous waste management; Microbial transformation reactions (aerobic and anaerobic biotransformations); Microbial detoxification of specialty chemicals (insecticides, herbicides, fungicides, polychlorinated biphenyls, heavy metals); Bioremediation systems and processes (solid, liquid and slurry phase bioremediation); Microbial cleaning of gases (biofiltration and bioscrubbing); In situ bioremediation; Laboratory scale biotreatability studies for bioremediation; Management of bioremediation project.

Semester I

Following courses will run in Sem I

Text Reference1. Stryer, L. (2015). Biochemistry. (8th ed.) New York: Freeman. 2. Lehninger, A. L. (2012). Principles of Biochemistry (6th ed.). New York, NY: Worth. 3. Voet, D., & Voet, J. G. (2016). Biochemistry (5th ed.). Hoboken, NJ: J. Wiley & Sons. 4. Dobson, C. M. (2003). Protein Folding and Misfolding. Nature, 426(6968), 884-890. doi:10.1038/nature02261. 5. Richards, F. M. (1991). The Protein Folding Problem. Scientific American, 264(1), 54-63. doi:10.1038/scientificamerican0191-54.
DescriptionChemical basis of life: Miller-Urey experiment, abiotic formation of amino acid oligomers, composition of living matter; Water – properties of water, essential role of water for life on earth pH, buffer, maintenance of blood pH and pH of gastric juice, pH optima of different enzymes (pepsin, trypsin and alkaline phosphatase), ionization and hydrophobicity, emergent properties of biomolecules in water, biomolecular hierarchy, macromolecules, molecular assemblies. Structure-function relationships: amino acids – structure and functional group properties, peptides and covalent structure of proteins, elucidation of primary and higher order structures, Ramachandran plot, evolution of protein structure, protein degradation and introduction to molecular pathways controlling protein degradation, structure-function relationships in model proteins like ribonuclease A, myoglobin, hemoglobin, chymotrypsin etc.; basic principles of protein purification; tools to characterize expressed proteins; Protein folding: Anfinsen’s Dogma, Levinthal paradox, cooperativity in protein folding, free energy landscape of protein folding and pathways of protein folding, molten globule state, chaperons, diseases associated with protein folding, introduction to molecular dynamic simulation. Enzyme catalysis – general principles of catalysis; quantitation of enzyme activity and efficiency; enzyme characterization and Michaelis-Menten kinetics; relevance of enzymes in metabolic regulation, activation, inhibition and covalent modification; single substrate enzymes; concept of catalytic antibodies; catalytic strategies with specific examples of proteases, carbonic anhydrases, restriction enzymes and nucleoside monophosphate kinase; regulatory strategies with specific example of hemoglobin; isozymes; role of covalent modification in enzymatic activity; zymogens. Sugars – mono, di, and polysaccharides with specific reference to glycogen, amylose and cellulose, glycosylation of other biomolecules – glycoproteins and glycolipids; lipids – structure and properties of important members of storage and membrane lipids; lipoproteins. Self-assembly of lipids, micelle, biomembrane organization – sidedness and function; membrane bound proteins – structure, properties and function; transport phenomena; nucleosides, nucleotides, nucleic acids – structure, a historical perspective leading up to the proposition of DNA double helical structure; difference in RNA and DNA structure and their importance in evolution of DNA as the genetic material. Bioenergetics-basic principles; equilibria and concept of free energy; coupled interconnecting reactions in metabolism; oxidation of carbon fuels; recurring motifs in metabolism; Introduction to GPCR, Inositol/DAG//PKC and Ca++ signaling pathways; glycolysis and gluconeogenesis; reciprocal regulations and non-carbohydrate sources of glucose; Citric acid cycle, entry to citric acid cycle, citric acid cycle as a source of biosynthetic precursors; Oxidative phosphorylation; importance of electron transfer in oxidative phosphorylation; F1- F0 ATP Synthase; shuttles across mitochondria; regulation of oxidative phosphorylation; Photosynthesis – chloroplasts and two photosystems; proton gradient across thylakoid membrane; Calvin cycle and pentose phosphate pathway; glycogen metabolism, reciprocal control of glycogen synthesis and breakdown, roles of epinephrine and glucagon and insulin in glycogen metabolism; Fatty acid metabolism; protein turnover and amino acid catabolism; nucleotide biosynthesis; biosynthesis of membrane lipids and sterols with specific emphasis on cholesterol metabolism and mevalonate pathway; elucidation of metabolic pathways; logic and integration of central metabolism; entry/ exit of various biomolecules from central pathways; principles of metabolic regulation; steps for regulation. Calvin cycle and pentose phosphate pathway; glycogen metabolism, reciprocal control of glycogen synthesis and breakdown, roles of epinephrine and glucagon and insulin in glycogen metabolism; Fatty acid metabolism; protein turnover and amino acid catabolism; nucleotide biosynthesis; biosynthesis of membrane lipids and sterols with specific emphasis on cholesterol metabolism and mevalonate pathway; elucidation of metabolic pathways; logic and integration of central metabolism; entry/ exit of various biomolecules from central pathways; principles of metabolic regulation; steps for regulation; target of rapamycin (TOR) & Autophagy regulation in relation to C & N metabolism, starvation responses and insulin signaling.

 

Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2008). Molecular Biology of the Cell (5th Ed.). New York: Garland Science. 2. Lodish, H. F. (2016). Molecular Cell Biology (8th Ed.). New York: W.H. Freeman. 3. Krebs, J. E., Lewin, B., Kilpatrick, S. T., & Goldstein, E. S. (2014). Lewin`s Genes XI. Burlington, MA: Jones & Bartlett Learning. 4. Cooper, G. M., & Hausman, R. E. (2013). The Cell: a Molecular Approach (6th Ed.). Washington: ASM ; Sunderland. 5. Hardin, J., Bertoni, G., Kleinsmith, L. J., & Becker, W. M. (2012). Becker`s World of the Cell. Boston (8th Ed.). Benjamin Cummings. 6. Watson, J. D. (2008). Molecular Biology of the Gene (5th ed.). Menlo Park, CA: Benjamin/Cummings.
DescriptionUniversal features of cells; cell chemistry and biosynthesis: chemical organization of cells; internal organization of the cell – cell membranes: structure of cell membranes and concepts related to compartmentalization in eukaryotic cells; intracellular organelles: endoplasmic reticulum and Golgi apparatus, lysosomes and peroxisomes, ribosomes, cellular cytoskeleton, mitochondria, chloroplasts and cell energetics; nuclear compartment: nucleus, nucleolus and chromosomes. Chromatin organization – histone and DNA interactome: structure and assembly of eukaryotic and prokaryotic DNA polymerases, DNA-replication, repair and recombination; chromatin control: gene transcription and silencing by chromatin Writers,-Readers and –Erasers; Transcriptional control: Structure and assembly of eukaryotic and prokaryotic RNA Polymerases, promoters and enhancers, transcription factors as activators and repressors, trancriptional initiation, elongation and termination; post-transcriptional control: splicing and addition of cap and tail, mRNA flow through nuclear envelope into cytoplasm, breakdown of selective and specific mRNAs through interference by small non-coding RNAs (miRNAs and siRNAs), protein translation machinery, ribosomes-composition and assembly; universal genetic codes, degeneracy of codons, Wobble hypothesis; Iso-accepting tRNA; mechanism of initiation, elongation and termination; co- and post-translational modifications, mitochondrial genetic code translation product cleavage, modification and activation. Molecular mechanisms of membrane transport, nuclear transport, transport across mitochondria and chloroplasts; intracellular vesicular trafficking from endoplasmic reticulum through Golgi apparatus to lysosomes/cell exterior. Cell cycle and its regulation; cell division: mitosis, meiosis and cytokinesis; cell differentiation: stem cells, their differentiation into different cell types and organization into specialized tissues; cell-ECM and cell-cell interactions; cell receptors and transmembrane signalling; cell motility and migration; cell death: different modes of cell death and their regulation. Isolation of cells and basics of cell culture; observing cells under a microscope, different types of microscopy; analyzing and manipulating DNA, RNA and proteins. Mutations, proto-oncogenes, oncogenes and tumour suppressor genes, physical, chemical and biological mutagens; types of mutations; intra-genic and inter-genic suppression; transpositions- transposable genetic elements in prokaryotes and eukaryotes, role of transposons in genome; viral and cellular oncogenes; tumor suppressor genes; structure, function and mechanism of action; activation and suppression of tumor suppressor genes; oncogenes as transcriptional activators.

 

Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Chawla, H. S. (2000). Introduction to Plant Biotechnology. Enfield, NH: Science. 2. Razdan, M. K. (2003). Introduction to Plant Tissue Culture. Enfield, NH: Science. 3. Slater, A., Scott, N. W., & Fowler, M. R. (2008). Plant Biotechnology: an Introduction to Genetic Engineering. Oxford: Oxford University Press. 4. Buchanan, B. B., Gruissem, W., & Jones, R. L. (2015). Biochemistry & Molecular Biology of Plants. Chichester, West Sussex: John Wiley & Sons. 5. Umesha, S. (2013). Plant Biotechnology. The Energy And Resources. 6. Glick, B. R., & Pasternak, J. J. (2010). Molecular Biotechnology: Principles and Applications of Recombinant DNA. Washington, D.C.: ASM Press. 7. Brown, T. A. (2006). Gene Cloning and DNA Analysis: an Introduction. Oxford: Blackwell Pub. 8. Primrose, S. B., & Twyman, R. M. (2006). Principles of Gene Manipulation and Genomics. Malden, MA: Blackwell Pub. 9. Slater, A., Scott, N. W., & Fowler, M. R. (2003). Plant Biotechnology: The Genetic Manipulation of Plants. Oxford: Oxford University Press. 10. Gordon, I. (2005). Reproductive Techniques in Farm Animals. Oxford: CAB International. 11. Levine, M. M. (2004). New Generation Vaccines. New York: M. Dekker. 12. Pörtner, R. (2007). Animal Cell Biotechnology: Methods and Protocols. Totowa, NJ: Humana Press.
DescriptionPlant tissue culture: historical perspective; totipotency; organogenesis; Somatic embryogenesis; establishment of cultures – callus culture, cell suspension culture, media preparation – nutrients and plant hormones; sterilization techniques; applications of tissue culture – micropropagation; somaclonal variation; androgenesis and its applications in genetics and plant breeding; germplasm conservation and cryopreservation; synthetic seed production; protoplast culture and somatic hybridization – protoplast isolation; culture and usage; somatic hybridization – methods and applications; cybrids and somatic cell genetics; plant cell cultures for secondary metabolite production. Animal cell culture: brief history of animal cell culture; cell culture media and reagents; culture of mammalian cells, tissues and organs; primary culture, secondary culture, continuous cell lines, suspension cultures; application of animal cell culture for virus isolation and in vitro testing of drugs, testing of toxicity of environmental pollutants in cell culture, application of cell culture technology in production of human and animal viral vaccines and pharmaceutical proteins. Genetic engineering: Agrobacterium-plant interaction; virulence; Ti and Ri plasmids; opines and their significance; T-DNA transfer; disarmed Ti plasmid; Genetic transformation – Agrobacterium-mediated gene delivery; cointegrate and binary vectors and their utility; direct gene transfer – PEG-mediated, electroporation, particle bombardment and alternative methods; screenable and selectable markers; characterization of transgenics; chloroplast transformation; marker-free methodologies; advanced methodologies – cisgenesis, intragenesis and genome editing; molecular pharming – concept of plants as biofactories, production of industrial enzymes and pharmaceutically important compounds. Animal reproductive biotechnology: structure of sperms and ovum; cryopreservation of sperms and ova of livestock; artificial insemination; super ovulation, embryo recovery and in vitro fertilization; culture of embryos; cryopreservation of embryos; embryo transfer technology; transgenic manipulation of animal embryos; applications of transgenic animal technology; animal cloning – basic concept, cloning for conservation for conservation endangered species; Vaccinology: history of development of vaccines, introduction to the concept of vaccines, conventional methods of animal vaccine production, recombinant approaches to vaccine production, modern vaccines. Overview of genomics – definition, complexity and classification; need for genomics level analysis; methods of analyzing genome at various levels – DNA, RNA, protein, metabolites and phenotype; genome projects and bioinformatics resources for genome research – databases; overview of forward and reverse genetics for assigning function for genes. Molecular markers – hybridization and PCR based markers RFLP, RAPD, STS, SSR, AFLP, SNP markers; DNA fingerprinting-principles and applications; introduction to mapping of genes/QTLs; marker-assisted selection – strategies for Introducing genes of biotic and abiotic stress resistance in plants: genetic basis for disease resistance in animals; molecular diagnostics of pathogens in plants and animals; detection of meat adulteration using DNA based methods.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Pelczar, M. J., Reid, R. D., & Chan, E. C. (2001). Microbiology (5th ed.). New York: McGraw-Hill. 2. Willey, J. M., Sherwood, L., Woolverton, C. J., Prescott, L. M., & Willey, J. M. (2011). Prescott’s Microbiology. New York: McGraw-Hill. 3. Matthai, W., Berg, C. Y., & Black, J. G. (2005). Microbiology, Principles and Explorations. Boston, MA: John Wiley & Sons.
DescriptionIntroduction to microbiology and microbes, history & scope of microbiology, morphology, structure, growth and nutrition of bacteria, bacterial growth curve, bacterial culture methods; bacterial genetics: mutation and recombination in bacteria, plasmids, transformation, transduction and conjugation; antimicrobial resistance. Microbial taxonomy and evolution of diversity, classification of microorganisms, criteria for classification; classification of bacteria; Cyanobacteria, acetic acid bacteria, Pseudomonads, lactic and propionic acid bacteria, endospore forming bacteria, Mycobacteria and Mycoplasma. Archaea: Halophiles, Methanogens, Hyperthermophilic archae, Thermoplasm; eukarya: algae, fungi, slime molds and protozoa; extremophiles and unculturable microbes. Sterilization, disinfection and antisepsis: physical and chemical methods for control of microorganisms, antibiotics, antiviral and antifungal drugs, biological control of microorganisms. Virus and bacteriophages, general properties of viruses, viral structure, taxonomy of virus, viral replication, cultivation and identification of viruses; sub-viral particles – viroids and prions. Host-pathogen interaction, ecological impact of microbes; symbiosis (Nitrogen fixation and ruminant symbiosis); microbes and nutrient cycles; microbial communication system; bacterial quorum sensing; microbial fuel cells; prebiotics and probiotics.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Hartl, D. L., & Jones, E. W. (1998). Genetics: Principles and Analysis. Sudbury, MA: Jones and Bartlett. 2. Pierce, B. A. (2005). Genetics: a Conceptual Approach. New York: W.H. Freeman. 3. Tamarin, R. H., & Leavitt, R. W. (1991). Principles of Genetics. Dubuque, IA: Wm. C. Brown. 4. Smith, J. M. (1998). Evolutionary Genetics. Oxford: Oxford University Press.
DescriptionConcept of a gene in pre-DNA era; mapping of genes in bacterial and phage chromosomes by classical genetic crosses; fine structure analysis of a gene; genetic complementation and other genetic crosses using phenotypic markers; phenotype to genotype connectivity prior to DNA- based understanding of gene. Meiotic crosses, tetrad analyses, non-Mendelian and Mendelian ratios, gene conversion, models of genetic recombination, yeast mating type switch; dominant and recessive genes/mutations, suppressor or modifier screens, complementation groups, transposon mutagenesis, synthetic lethality, genetic epistasis. Monohybrid & dihybrid crosses, back-crosses, test-crosses, analyses of autosomal and sex linkages, screening of mutations based on phenotypes and mapping the same, hypomorphy, genetic mosaics, genetic epistasis in context of developmental mechanism. Introduction to the elements of population genetics: genetic variation, genetic drift, neutral evolution; mutation selection, balancing selection, Fishers theorem, HardyWeinberg equilibrium, linkage disequilibrium; in-breeding depression & mating systems; population bottlenecks, migrations, Bayesian statistics; adaptive landscape, spatial variation & genetic fitness. Complex traits, mapping QTLs, yeast genomics to understand biology of QTLs. Laws of segregation in plant crosses, inbreeding, selfing, heterosis, maintenance of genetic purity, gene pyramiding.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Stroud, K. A., & Booth, D. J. (2009). Foundation Mathematics. New York, NY: Palgrave Macmillan. 2. Aitken, M., Broadhursts, B., & Haldky, S. (2009) Mathematics for Biological Scientists. Garland Science. 3. Billingsley, P. (1986). Probability and Measure. New York: Wiley. 4. Rosner, B. (2000). Fundamentals of Biostatistics. Boston, MA: Duxbury Press. 5. Daniel, W. W. (1987). Biostatistics, a Foundation for Analysis in the Health Sciences. New York: Wiley.
DescriptionLinear equations, functions: slopes-intercepts, forms of two-variable linear equations; constructing linear models in biological systems; quadratic equations (solving, graphing, features of, interpreting quadratic models etc.), introduction to polynomials, graphs of binomials and polynomials; Symmetry of polynomial functions, basics of trigonometric functions, Pythagorean theory, graphing and constructing sinusoidal functions, imaginary numbers, complex numbers, adding-subtracting-multiplying complex numbers, basics of vectors, introduction to matrices. Differential calculus (limits, derivatives), integral calculus (integrals, sequences and series etc.). Population dynamics; oscillations, circadian rhythms, developmental patterns, symmetry in biological systems, fractal geometries, size-limits & scaling in biology, modeling chemical reaction networks and metabolic networks. Probability: counting, conditional probability, discrete and continuous random variables; Error propagation; Populations and samples, expectation, parametric tests of statistical significance, nonparametric hypothesis tests, linear regression, correlation & causality, analysis of variance, factorial experiment design.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Baaquie, B. E. (2000). Laws of Physics: a Primer. Singapore: National University of Singapore. 2. Matthews, C. P., & Shearer, J. S. (1897). Problems and Questions in Physics. New York: Macmillan Company. 3. Halliday, D., Resnick, R., & Walker, J. (1993). Fundamentals of Physics. New York: Wiley. 4. Ebbing, D. D., & Wrighton, M. S. (1990). General Chemistry. Boston: Houghton Mifflin. 5. Averill, B., & Eldredge, P. (2007). Chemistry: Principles, Patterns, and Applications. San Francisco: Benjamin Cummings. 6. Mahan, B. H. (1965). University Chemistry. Reading, MA: Addison-Wesley Pub. 7. Cantor, C. R., & Schimmel, P. R. (2004). Biophysical Chemistry. San Francisco: W.H. Freeman.
DescriptionPhysical quantities and their dynamics: definitions and dimensions; vectors & scalars, displacement, velocity, acceleration, kinematic formulas, angular momentum, torque etc. force, power, work, energy (kinetic & potential/electric charge separation, electromagnetic spectrum, photons etc.); springs & Hookes laws; elastic and inelastic collisions; Newton’s law of motions (centripetal and centrifugal forces etc.); simple harmonic motions, mechanical waves, Doppler effect, wave interference, amplitude, period, frequency & wavelength; diffusion, dissipation, random walks, and directed motions in biological systems; low Reynolds number – world of Biology, buoyant forces, Bernoulli’s equation, viscosity, turbulence, surface tension, adhesion; laws of thermodynamics: Maxwell Boltzmann distribution, conduction, convection and radiation, internal energy, entropy, temperature and free energy, Maxwell’s demon (entropic forces at work in biology, chemical assemblies, self-assembled systems, role of ATP); Coulomb’s law, conductors and insulators, electric potential energy of charges, nerve impulses, voltage gated channels, ionic conductance; Ohms law (basic electrical quantities: current, voltage & power), electrolyte conductivity, capacitors and capacitance, dielectrics; various machines in biology i.e. enzymes, allostery and molecular motors (molecules to cells and organisms). Basic constituents of matter – elements, atoms, isotopes, atomic weights, atomic numbers, basics of mass spectrometry, molecules, Avogadro number, molarity, gas constant, molecular weights, structural and molecular formulae, ions and polyatomic ions; chemical reactions, reaction stoichiometry, rates of reaction, rate constants, order of reactions, Arrhenious equation, Maxwell Boltzmann distributions, ratedetermining steps, catalysis, free-energy, entropy and enthalpy changes during reactions; kinetic versus thermodynamic controls of a reaction, reaction equilibrium (equilibrium constant); light and matter interactions (optical spectroscopy, fluorescence, bioluminescence, paramagnetism and diamagnetism, photoelectron spectroscopy; chemical bonds (ionic, covalent, Van der Walls forces); electronegativity, polarity; VSEPR theory and molecular geometry, dipole moment, orbital hybridizations; states of matter – vapor pressure, phase diagrams, surface tension, boiling and melting points, solubility, capillary action, suspensions, colloids and solutions; acids, bases and pH – Arrhenious theory, pH, ionic product of water, weak acids and bases, conjugate acid-base pairs, buffers and buffering action etc; chemical thermodynamics – internal energy, heat and temperature, enthalpy (bond enthalpy and reaction enthalpy), entropy, Gibbs free energy of ATP driven reactions, spontaneity versus driven reactions in biology; redox reactions and electrochemistry – oxidation-reduction reactions, standard cell potentials, Nernst equation, resting membrane potentials, electron transport chains (ETC) in biology, coupling of oxidative phosphorylations to ETC; theories of ATP production and dissipation across biological membranes; bond rotations and molecular conformations – Newman projections, conformational analysis of alkanes, alkenes and alkynes; functional groups, optically asymmetric carbon centers, amino acids, proteins, rotational freedoms in polypeptide backbone (Ramachandran plot).
Text Reference1.011C.G. Cooper; Tools of Biochemistry, Wiley Interscience, 1977.2.011E.D. Holme & H. Peck; Analytical Biochemistry, Longman, 1983.3.011R. Scopes; Protein Purification – Principles and Practices, Springer Verlag, 1982.4.011R.C. Price., Proteins. Lafbax Academic Press, 1996.5.011I. H.Segel., Biochemical calculations. Wiley, 1975.6.011K. Wilson & J. Walker, Principles and techniques of biochemistry and molecular biology. Cambridge University Press, 2010.7.011Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1-2), 248-254.8.011Lowry, O. H., Rosebraugh, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of biological chemistry, 193, 265-275.9.011Miller, G. L. (1959). Use of dinitrosalicylic acid reagent for determination of reducing sugar. Analytical Chemistry, 31(3), 426-428.
Description1.011Preparing various stock solutions and working solutions that will be needed for the course.2.011To prepare an Acetic-Na Acetate Buffer and validate the Henderson-Hasselbach equation.3.011To determine an unknown protein concentration by plotting a standard graph of BSA using UV-Vis Spectrophotometer and validating the Beer- Lambert302222s Law.4.011Titration of Amino Acids and separation of aliphatic, aromatic and polar amino acids by thin layer chromatography.5.011Purification and characterization of an enzyme from a recombinant source (such as Alkaline Phosphatase or Lactate Dehydrogenase or any enzyme of the institution302222s choice). a) Preparation of cell-free lysates; b) Ammonium Sulfate precipitation; c) Ion-exchange Chromatography; d) Gel Filtration; e) Affinity Chromatography; f) Dialysis of the purified protein solution against 60% glycerol as a demonstration of storage method; g) Generating a Purification Table (protein concentration, amount of total protein; Computing specific activity of the enzyme preparation at each stage of purification); h) Assessing purity of samples from each step of purification by SDS-PAGE Gel Electrophoresis; i) Enzyme Kinetic Parameters: Km, Vmax and Kcat.6.011Experimental verification that absorption at OD260 is more for denatured DNA as compared to native double stranded DNA. Reversal of the same following DNA renaturation. Kinetics of DNA renaturation as a function of DNA size.7.011Identification of an unknown sample as DNA, RNA or protein using available laboratory tools. (Optional Experiments)8.011Biophysical methods (Circular Dichroism Spectroscopy, Fluorescence Spectroscopy).9.011Determination of mass of small molecules and fragmentation patterns by Mass Spectrometry.
Text ReferenceTitle, Authors, Edition, Publisher, Year1.011Cappuccino, J. G., & Welsh, C. (2016). Microbiology: a Laboratory Manual. Benjamin-Cummings Publishing Company.2.011Collins, C. H., Lyne, P. M., Grange, J. M., & Falkinham III, J. (2004). Collins and Lyne302222s Microbiological Methods (8th ed.). Arnolds.3.011Tille, P. M., & Forbes, B. A. (2014) Bailey & Scott302222s Diagnostic Microbiology
Description1.011Sterilization, disinfection and safety in microbiological laboratory.2.011Preparation of media for cultivation of bacteria.3.011Isolation of bacteria in pure culture by streak plate method.4.011Study of colony and growth characteristics of some common bacteria: Bacillus, E. coli, Staphylococcus, Streptococcus, etc.5.011Preparation of bacterial smear and Gram302222s staining.6.011Enumeration of bacteria: standard plate count.7.011Antimicrobial sensitivity test and demonstration of drug resistance.8.011Maintenance of stock cultures: slants, stabs and glycerol stock cultures9.011Determination of phenol co-efficient of antimicrobial agents.10.011Determination of Minimum Inhibitory Concentration (MIC)11.011Isolation and identification of bacteria from soil/water samples.
Text Reference1.011Biotechnology: Theory and techniques of Plant Biotechnology, Animal cell culture and Immunobiotechnology vols 1 and 2 by Jack K Chirikjian, 20092.011Plant Biotechnology and its applications in Plant tissue cultureby Ashwani Kumar and Shikha Roy, 20063.011Culture of Animal Cells: A Manual of Basic Technique by R. Ian Freshney, 20104.011General Techniques of Cell Culture Handbooks in Practical Animal Cell Biology by Maureen A Journal articles and reviews, 1997
DescriptionPlant Biotechnology1. Prepare culture media with various supplements for plant tissue culture.2. Prepare explants of Valleriana wallichii for inoculation under aseptic conditions.3. Attempt in vitro andro and gynogenesis in plants (Datura stramonium).4. Isolate plant protoplast by enzymatic and mechanical methods and attempt fusion by PEG (available material).5. Culture Agrobacterium tumefaciens and attempt transformation of any dicot species.6. Generate an RAPD and ISSR profile of Eremurus persicus and Valleriana wallichii.7. Prepare karyotypes and study the morphology of somatic chromosomes of Allium cepa, A. sativum, A. tuberosum and compare them on the basis of karyotypes.8. Pollen mother cell meiosis and recombination index of select species (one achiasmate, and the other chiasmate) and correlate with generation of variation.9. Undertake plant genomic DNA isolation by CTAB method and its quantitation by visual as well as spectrophotometeric methods.10. Perform PCR amplification of 302221n302222 number of genotypes of a species for studying the genetic variation among the individuals of a species using random primers.11. Study genetic fingerprinting profiles of plants and calculate polymorphic information content.Animal Biotechnology1. Count cells of an animal tissue and check their viability.2. Prepare culture media with various supplements for plant and animal tissue culture.3. Prepare single cell suspension from spleen and thymus.4. Monitor and measure doubling time of animal cells.5. Chromosome preparations from cultured animal cells.6. Isolate DNA from animal tissue by SDS method.7. Attempt animal cell fusion using PEG.

Semester II

Following courses will run in Sem II

Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Old, R. W., Primrose, S. B., & Twyman, R. M. (2001). Principles of Gene Manipulation: an Introduction to Genetic Engineering. Oxford: Blackwell Scientific Publications. 2. Green, M. R., & Sambrook, J. (2012). Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. 3. Brown, T. A. (2006). Genomes (3rd ed.). New York: Garland Science Pub. 4. Selected papers from scientific journals, particularly Nature & Science. 5. Technical Literature from Stratagene, Promega, Novagen, New England Biolab
DescriptionImpact of genetic engineering in modern society; general requirements for performing a genetic engineering experiment; restriction endonucleases and methylases; DNA ligase, Klenow enzyme, T4 DNA polymerase, polynucleotide kinase, alkaline phosphatase; cohesive and blunt end ligation; linkers; adaptors; homopolymeric tailing; labelling of DNA: nick translation, random priming, radioactive and non-radioactive probes, hybridization techniques: northern, southern, south-western and far-western and colony hybridization, fluorescence in situ hybridization. Plasmids; Bacteriophages; M13 mp vectors; PUC19 and Bluescript vectors, hagemids; Lambda vectors; Insertion and Replacement vectors; Cosmids; Artificial chromosome vectors (YACs; BACs); Principles for maximizing gene expression expression vectors; pMal; GST; pET-based vectors; Protein purification; His-tag; GST-tag; MBP-tag etc.; Intein-based vectors; Inclusion bodies; methodologies to reduce formation of inclusion bodies; mammalian expression and replicating vectors; Baculovirus and Pichia vectors system, plant based vectors, Ti and Ri as vectors, yeast vectors, shuttle vectors. Principles of PCR: primer design; fidelity of thermostable enzymes; DNA polymerases; types of PCR – multiplex, nested; reverse-transcription PCR, real time PCR, touchdown PCR, hot start PCR, colony PCR, asymmetric PCR, cloning of PCR products; T-vectors; proof reading enzymes; PCR based site specific mutagenesis; PCR in molecular diagnostics; viral and bacterial detection; sequencing methods; enzymatic DNA sequencing; chemical sequencing of DNA; automated DNA sequencing; RNA sequencing; chemical synthesis of oligonucleotides; mutation detection: SSCP, DGGE, RFLP. Insertion of foreign DNA into host cells; transformation, electroporation, transfection; construction of libraries; isolation of mRNA and total RNA; reverse transcriptase and cDNA synthesis; cDNA and genomic libraries; construction of microarrays – genomic arrays, cDNA arrays and oligo arrays; study of protein-DNA interactions: electrophoretic mobility shift assay; DNase footprinting; methyl interference assay, chromatin immunoprecipitation; protein- protein interactions using yeast two-hybrid system; phage display. Gene silencing techniques; introduction to siRNA; siRNA technology; Micro RNA; construction of siRNA vectors; principle and application of gene silencing; gene knockouts and gene therapy; creation of transgenic plants; debate over GM crops; introduction to methods of genetic manipulation in different model systems e.g. fruit flies (Drosophila), worms (C. elegans), frogs (Xenopus), fish (zebra fish) and chick; Transgenics – gene replacement; gene targeting; creation of transgenic and knock-out mice; disease model; introduction to genome editing by CRISPR-CAS with specific emphasis on Chinese and American clinical trials.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Kindt, T. J., Goldsby, R. A., Osborne, B. A., & Kuby, J. (2006). Kuby Immunology. New York: W.H. Freeman. 2. Brostoff, J., Seaddin, J. K., Male, D., & Roitt, I. M. (2002). Clinical Immunology. London: 3. Gower Medical Pub. 4. Murphy, K., Travers, P., Walport, M., & Janeway, C. (2012). Janeway’s Immunobiology. New York: Garland Science. 5. Paul, W. E. (2012). Fundamental Immunology. New York: Raven Press. 6. Goding, J. W. (1996). Monoclonal Antibodies: Principles and Practice: Production and Application of Monoclonal Antibodies in Cell Biology, Biochemistry, and Immunology. London: Academic Press. 7. Parham, P. (2005). The Immune System. New York: Garland Science.
DescriptionComponents of innate and acquired immunity; phagocytosis; complement and inflammatory responses; pathogen recognition receptors (PRR) and pathogen associated molecular pattern (PAMP); innate immune response; mucosal immunity; antigens: immunogens, haptens; Major Histocompatibility Complex: MHC genes, MHC and immune responsiveness and disease susceptibility, Organs of immune system, primary and secondary lymphoid organs. Immunoglobulins – basic structure, classes & subclasses of immunoglobulins, antigenic determinants; multigene organization of immunoglobulin genes; B-cell receptor; Immunoglobulin superfamily; principles of cell signaling; basis of self & non-self discrimination; kinetics of immune response, memory; B cell maturation, activation and differentiation; generation of antibody diversity; T-cell maturation, activation and differentiation and T-cell receptors; functional T Cell subsets; cell-mediated immune responses, ADCC; cytokines: properties, receptors and therapeutic uses; antigen processing and presentation- endogenous antigens, exogenous antigens, non-peptide bacterial antigens and super-antigens; cell-cell co-operation, Hapten-carrier system. Precipitation, agglutination and complement mediated immune reactions; advanced immunological techniques: RIA, ELISA, Western blotting, ELISPOT assay, immunofluorescence microscopy, flow cytometry and immunoelectron microscopy; surface plasmon resonance, biosensor assays for assessing ligand –receptor interaction; CMI techniques: lymphoproliferation assay, mixed lymphocyte reaction, cell cytotoxicity assays, apoptosis, microarrays, transgenic mice, gene knock outs. Active and passive immunization; live, killed, attenuated, subunit vaccines; vaccine technology: role and properties of adjuvants, recombinant DNA and protein based vaccines, plant-based vaccines, reverse vaccinology; peptide vaccines, conjugate vaccines; antibody genes and antibody engineering:chimeric, generation of monoclonal antibodies, hybrid monoclonal antibodies; catalytic antibodies and generation of immunoglobulin gene libraries, idiotypic vaccines and marker vaccines, viral-like particles (VLPs), dendritic cell based vaccines, vaccine against cancer, T cell based vaccine, edible vaccine and therapeutic vaccine. Immunity to infection : bacteria, viral, fungal and parasitic infections (with examples from each group); hypersensitivity: Type I-IV; autoimmunity; types of autoimmune diseases; mechanism and role of CD4+ T cells; MHC and TCR in autoimmunity; treatment of autoimmune diseases; transplantation: immunological basis of graft rejection; clinical transplantation and immunosuppressive therapy; tumor immunology: tumor antigens; immune response to tumors and tumor evasion of the immune system, cancer immunotherapy; immunodeficiency: primary immunodeficiencies, acquired or secondary immunodeficiencies, autoimmune disorder, anaphylactic shock, immunosenescence, immune exhaustion in chronic viral infection, immune tolerance, NK cells in chronic viral infection and malignancy. Major histocompatibility complex genes and their role in autoimmune and infectious diseases, HLA typing, human major histocompatibility complex (MHC), Complement genes of the human major histocompatibility complex: implication for linkage disequilibrium and disease associations, genetic studies of rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis, genetics of human immunoglobulin, immunogenetics of spontaneous control of HIV, KIR complex.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Lesk, A. M. (2002). Introduction to Bioinformatics. Oxford: Oxford University Press. 2. Mount, D. W. (2001). Bioinformatics: Sequence and Genome Analysis. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. 3. Baxevanis, A. D., & Ouellette, B. F. (2001). Bioinformatics: a Practical Guide to the Analysis of Genes and Proteins. New York: Wiley-Interscience. 4. Pevsner, J. (2015). Bioinformatics and Functional Genomics. Hoboken, NJ.: Wiley- Blackwell. 5. Bourne, P. E., & Gu, J. (2009). Structural Bioinformatics. Hoboken, NJ: Wiley-Liss. 6. Lesk, A. M. (2004). Introduction to Protein Science: Architecture, Function, and Genomics. Oxford: Oxford University Press.
DescriptionBioinformatics basics: Searching PubMed, current content, science citation index and current awareness services, electronic journals, grants and funding information. Computers in biology and medicine; Introduction to Unix and Linux systems and basic commands; Database concepts; Protein and nucleic acid databases; Structural databases; Biological XML DTD’s; pattern matching algorithm basics; databases and search tools: biological background for sequence analysis; Identification of protein sequence from DNA sequence; searching of databases similar sequence; NCBI; publicly available tools; resources at EBI; resources on web; database mining tools. BLAST: sequence alignment- methods, evaluation, scoring; Use of various primer designing and restriction site prediction tools. Use of miRNA prediction, designing and target prediction tools. DNA sequence analysis: gene bank sequence database; submitting DNA sequences to databases and database searching; sequence alignment; pairwise alignment techniques; motif discovery and gene prediction (GRAIL, Genscan, Glimmer); local structural variants of DNA, their relevance in molecular level processes, and their identification; assembly of data from genome sequencing. Multiple sequence analysis; multiple sequence alignment; flexible sequence similarity searching with the FASTA3 program package; use of CLUSTALW and CLUSTALX for multiple sequence alignment; submitting DNA protein sequence to databases: where and how to submit, SEQUIN, genome centres; submitting aligned sets of sequences, updating submitted sequences, methods of phylogenetic analysis.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Primrose, S. B., Twyman, R. M., Primrose, S. B., & Primrose, S. B. (2006). Principles of Gene Manipulation and Genomics. Malden, MA: Blackwell Pub. 2. Liebler, D. C. (2002). Introduction to Proteomics: Tools for the New Biology. Totowa, NJ: Humana Press. 3. Campbell, A. M., & Heyer, L. J. (2003). Discovering Genomics, Proteomics, and Bioinformatics. San Francisco: Benjamin Cummings.
DescriptionBrief overview of prokaryotic and eukaryotic genome organization; extra-chromosomal DNA: bacterial plasmids, mitochondria and chloroplast. Genetic and physical maps; markers for genetic mapping; methods and techniques used for gene mapping, physical mapping, linkage analysis, cytogenetic techniques, FISH technique in gene mapping, somatic cell hybridization, radiation hybrid maps, in situ hybridization, comparative gene mapping. Human Genome Project, genome sequencing projects for microbes, plants and animals, accessing and retrieving genome project information from the web. Identification and classification of organisms using molecular markers- 16S rRNA typing/sequencing, SNPs; use of genomes to understand evolution of eukaryotes, track emerging diseases and design new drugs; determining gene location in genome sequence. Aims, strategies and challenges in proteomics; proteomics technologies: 2D-PAGE, isoelectric focusing, mass spectrometry, MALDI-TOF, yeast 2-hybrid system, proteome databases. Transcriptome analysis for identification and functional annotation of gene, Contig assembly, chromosome walking and characterization of chromosomes, mining functional genes in genome, gene function- forward and reverse genetics, gene ethics; protein-protein and protein- DNA interactions; protein chips and functional proteomics; clinical and biomedical applications of proteomics; introduction to metabolomics, lipidomics, metagenomics and systems biology.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Campbell, A. M., & Heyer, L. J. (2006). Discovering Genomics, Proteomics, and Bioinformatics. San Francisco: Benjamin Cummings. 2. Brooker, R. J. (2009). Genetics: Analysis & Principles. New York, NY: McGraw-Hill. 20 3. Glick, B. R., Pasternak, J. J., & Patten, C. L. (2010). Molecular Biotechnology: Principles and Applications of Recombinant DNA. Washington, DC: ASM Press. 4. Coleman, W. B., & Tsongalis, G. J. (2010). Molecular Diagnostics: for the Clinical Laboratorian. Totowa, NJ: Humana Press
DescriptionDNA, RNA, Protein: An overview; chromosomal structure & mutations; DNA polymorphism: human identity; clinical variability and genetically determined adverse reactions to drugs. PCR: Real-time; ARMS; Multiplex; ISH; FISH; ISA; RFLP; DHPLC; DGGE; CSCE; SSCP; Nucleic acid sequencing: new generations of automated sequencers; Microarray chips; EST; SAGE; microarray data normalization & analysis; molecular markers: 16S rRNA typing; Diagnostic proteomics: SELDI-TOF-MS; Bioinformatics data acquisition & analysis. Metabolite profile for biomarker detection the body fluids/tissues in various metabolic disorders by making using LCMS & NMR technological platforms. Direct detection and identification of pathogenic-organisms that are slow growing or currently lacking a system of in vitro cultivation as well as genotypic markers of microbial resistance to specific antibiotics. Exemplified by two inherited diseases for which molecular diagnosis has provided a dramatic improvement of quality of medical care: Fragile X Syndrome: Paradigm of new mutational mechanism of unstable triplet repeats, von-Hippel Lindau disease: recent acquisition in growing number of familial cancer syndromes. Detection of recognized genetic aberrations in clinical samples from cancer patients; types of cancer-causing alterations revealed by next-generation sequencing of clinical isolates; predictive biomarkers for personalized onco-therapy of human diseases such as chronic myeloid leukemia, colon, breast, lung cancer and melanoma as well as matching targeted therapies with patients and preventing toxicity of standard systemic therapies. Quality oversight; regulations and approved testing.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Valiela, I. (2001). Doing Science: Design, Analysis, and Communication of Scientific Research. Oxford: Oxford University Press. 2. On Being a Scientist: a Guide to Responsible Conduct in Research. (2009). Washington, D.C.: National Academies Press. 3. Gopen, G. D., & Smith, J. A. The Science of Scientific Writing. American Scientist, 78 (Nov-Dec 1990), 550-558. 4. Mohan, K., & Singh, N. P. (2010). Speaking English Effectively. Delhi: Macmillan India. 5. Movie: Naturally Obsessed, The Making of a Scientist.
DescriptionEmpirical science; scientific method; manipulative experiments and controls; deductive and inductive reasoning; descriptive science; reductionist vs holistic biology. Choosing a mentor, lab and research question; maintaining a lab notebook. Concept of effective communication- setting clear goals for communication; determining outcomes and results; initiating communication; avoiding breakdowns while communicating; creating value in conversation; barriers to effective communication; non-verbal communication-interpreting non-verbal cues; importance of body language, power of effective listening; recognizing cultural differences; Presentation skills – formal presentation skills; preparing and presenting using over-head projector, PowerPoint; defending interrogation; scientific poster preparation & presentation; participating in group discussions; Computing skills for scientific research – web browsing for information search; search engines and their mechanism of searching; hidden Web and its importance in scientific research; internet as a medium of interaction between scientists; effective email strategy using the right tone and conciseness. Technical writing skills – types of reports; layout of a formal report; scientific writing skills – importance of communicating science; problems while writing a scientific document; plagiarism, software for plagiarism; scientific publication writing: elements of a scientific paper including abstract, introduction, materials & methods, results, discussion, references; drafting titles and framing abstracts; publishing scientific papers – peer review process and problems, recent developments such as open access and non-blind review; plagiarism; characteristics of effective technical communication; scientific presentations; ethical issues; scientific misconduct.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Green, M. R., & Sambrook, J. (2012). Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press 2. Molecular Biology Techniques A Classroom Laboratory Manual, 4th Edition Susan Carson, Academic Press Elsevier, 2019, ISBN: 978-0-12-818024-2 3. Molecular Biology Problem Solver: A Laboratory Guide, Edited by Alan S. Gerstein, 2001, ISBNs: 0-471-37972-7 4. Novagen pET System Manual 11th Edition, 2011, www.merck4biosciences.com.
Description1. Concept of lac-operon: a) Lactose induction of B-galactosidase. b) Glucose Repression. c) Diauxic growth curve of E.coli 2. UV mutagenesis to isolate amino acid auxotroph 3. Phage titre with epsilon phage/M13 4. Genetic Transfer-Conjugation, gene mapping 5. Plasmid DNA isolation and DNA quantitation 6. Restriction Enzyme digestion of plasmid DNA 7. Agarose gel electrophoresis 8. Polymerase Chain Reaction and analysis by agarose gel electrophoresis 9. Vector and Insert Ligation 10. Preparation of competent cells 11. Transformation of E.coli with standard plasmids, Calculation of transformation efficiency 12. Confirmation of the insert by Colony PCR and Restriction mapping 13. Expression of recombinant protein, concept of soluble proteins and inclusion body formation in E.coli, SDS-PAGE analysis 14. Purification of His-Tagged protein on Ni-NTA columns a) Random Primer labeling b) Southern hybridization.
Text Reference1. Janeway’s Immunobiology by Kenneth Murphy, 8th Edition, 2012, Publisher: Garland 2. Roitt’s Essential Immunology by Peter J. Delves, Seamus J. Martin, Dennis R. Burton, and Ivan M. Roitt, 13th Edition, 2017. 3. Journal: Current protocols in Immunology: is a comprehensive source for protocols and overviews in the field of immunology including, in vivo and in vitro assays to study lymphocyte cells, the isolation and differentiation of stem and progenitor cells, flow cytometry and cell sorting, and animal models of infections disease. Online ISSN:1934-368X, A Wiley brand.
Description1. Selection of animals, preparation of antigens, immunization and methods of blood collection, serum separation and storage. 2. Antibody titre by ELISA method. 3. Double diffusion, Immuno-electrophoresis and Radial Immuno diffusion. 4. Complement fixation test. 5. Isolation and purification of IgG from serum or IgY from chicken egg. 6. SDS-PAGE, Immunoblotting, Dot blot assays. 7. Blood smear identification of leucocytes by Giemsa stain. 8. Separation of leucocytes by dextran method. 9. Demonstration of Phagocytosis of latex beads and their cryopreservation. 10. Separation of mononuclear cells by Ficoll-Hypaque and their cryopreservation. 11. Demonstration of ELISPOT. 12. Demonstration of FACS.

Elective I

Elective I

Elective I courses

Text Reference
  1. M. Evans and J. C. Furlong (2003), Environmental Biotechnology: Theory and Applications, Wiley Publishers.
  2. Ritmann and P. L. McCarty, (2000), Environmental Biotechnology: Principle & Applications, 2nd Ed., McGraw Hill Science.
  3. Scragg , (2005) Environmental Biotechnology. Pearson Education Limited.
  4. S. Devinny, M. A. Deshusses and T. S. Webster, (1998), Biofiltration for Air Pollution Control, CRC Press.
  5. J. Rehm and G. Reed, (2001), Biotechnology – A Multi-volume Comprehensive Treatise, Vol. 11, 2nd Ed., VCH Publishers Inc.
  6. H. S. Peavy, D. R. Rowe and G. Tchobanoglous, (2013), Environmental Engineering, McGraw-Hill Inc.
Description

Introduction to environment; pollution and its control; pollution indicators; waste management: domestic, industrial, solid and hazardous wastes; strain improvement; Biodiversity and its conservation; Role of microorganisms in geochemical cycles; microbial energy metabolism, microbial growth kinetics and elementary chemostat theory, relevant microbiological processes, microbial ecology.

Bioremediation: Fundamentals, methods and strategies of application (biostimulation, bioaugmentation) – examples, bioremediation of metals (Cr, As, Se, Hg), radionuclides (U, Te), organic pollutants (PAHs, PCBs, Pesticides, TNT etc.), technological aspects of bioremediation (in situ, ex situ).

Application of bacteria and fungi in bioremediation: White rot fungi vs specialized degrading bacteria: examples, uses and advantages vs disadvantages; Phytoremediation: Fundamentals and description of major methods of application (phytoaccumulation, phytovolatilization, rhizofiltration phytostabilization).

Bioinsecticides: Bacillus thuringiensis, Baculoviruses, uses, genetic modifications and aspects of safety in their use; Biofungicides: Description of mode of actions and mechanisms (e.g. Trichoderma, Pseudomonas fluorescens); Biofertilizers: Symbiotic systems between plants – microorganisms (nitrogen fixing symbiosis, mycorrhiza fungi symbiosis), Plant growth promoting rhizobacteria (PGPR) – uses, practical aspects and problems in application.

Environmental Biotechnology and biofuels: biogas; bioethanol; biodiesel; biohydrogen; Description of the industrial processes involved, microorganisms and biotechnological interventions for optimization of production; Microbiologically enhanced oil recovery (MEOR); Bioleaching of metals; Production of bioplastics; Production of biosurfactants: bioemulsifiers; Paper production: use of xylanases and white rot fungi.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. “Bacterial Pathogenesis: A molecular approach” by Brenda A. Wilson, ASM Press, 3rd edition, 2011. 2. “Mechanisms of Microbial Disease” by N. Cary Engleberg, Wolters Kluwer and Lippincott Williams & Wilkins, Fifth edition, 2013. 3. “Bacterial pathogenesis: Molecular and cellular mechanisms” by Camille Locht and Michel Simonet, Caister Academic Press, First edition, 2012.
DescriptionThe power of bacteria, Establishment of infectious diseases, Human microbiome, Biology of infectious agents, Animal and cell culture based models for studying infectious disease, Molecular approaches for identification of bacterial virulence factors, Microbial toxins, Delivery of virulence factors, Virulence regulation, Bacterial strategies for evasion of host defense mechanisms, Host-pathogen interactions, Bioterrorism.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Introduction to Biologic and Biosimilar Product Development and Analysis, Nagel, Karen M. Springer, 2018 2. Biosimilars: Regulatory, Clinical, and Biopharmaceutical Development Editors: Gutka, Hiten J., Yang, Harry, Kakar, Shefali (Eds.) Springer, 2018
DescriptionIntroduction to Biosimilars, Development and its role in Therapeutics, Cell Line Development and Upstream Bioprocessing, cell culture methods, clone selection and optimization, Bioreactors, Scale-up optimization Critical Quality Attributes for Biologics and Bio-similars, Glycosylation, De-amidation, Charge Variant analysis, Analytical Methods to measure Glycosylation, De-amidation, Charge Variant (AUC, CE, Mass spectrometry) Biophysical and analytical Characterization of Biologics products, Primary, secondary and tertiary structural analysis by various Biophysics Methods, Protein aggregation principle and analysis by DLS and SE-HPLC, Thermodynamic stability by DSC, ITC Downstream Purification for Biologics, Regulatory Approach for Biosimilars, Globalization of Biosimilars
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Methods in Modern Biophysics: B Nolting 2. Principles of Fluoresence Spectroscopy: J. R. LakowicZ 3. Confocal Microscopy: Methods and Protocols Editors: Paddock, Stephen W. (Ed.) 4. Introduction to Biosensors: Yoon, Jeong-Yeol 5. Methods in Cell biology: Academic press
DescriptionBiosensing, Biosensors; optical clinical chemistry, pH sensors, enzyme-linked immunosorbent assays, detection and quantification of DNA, RNA, proteins, enzymes, antibody, and receptors in tissues and organisms by various physicochemical techniques; DNA technology: molecular beacons, apatamers; single molecule detection, enzyme linked assays for detection of biological elements; spectroscopy and microscopy based sensors to determine concentrations of oxygen, glucose, and different analytes, optical and mass spectrometry based detection of disease markers, metabolites, and microorganism; photoinduced electron transfer probes for metal ions and anion sensors, and GFP-sensors
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Biothermodynamics: the study of biochemical processes at equilibrium, Edsall, J.T; Gutfreund, H; Chichester: John Wiley, 1983. 2. Biological thermodynamics, Haynie, D.T. Cambridge: Cambridge University Press, 2001. 3. Thermodynamics and kinetics for the biological sciences Hammes, G.G. J Wiley 2000.
DescriptionThermodynamic functions – U, A, H, S and G. The First law: work, heat, energy, heat transactions, enthalpy, standard enthalpy changes. The Second law: entropy, entropy changes accompanying specific processes; The Third law and Biology. Chemical equilibrium: Gibb’s energy minimum, description of equilibrium, How equilibria respond to pressure, temperature & pH. Applications of thermodynamic principles to biological systems. Statistical thermodynamics: distribution of molecular states (introduce molecular partition function), the internal & the statistical entropy, Boltzmann distribution.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Thermodynamics and kinetics for the biological sciences Hammes, G.G. J Wiley 2000. 2. Physical chemistry. 3rd ed. Atkins, P.W. Oxford, U.P., Oxford, 1986.
DescriptionBasic kinetic concepts: Reaction stoichiometry, rates of consumption & formation, extent of reaction, rate of reaction, Analysis of kinetic results, influence of temperature on reaction rates. Theories of reaction rates: Kinetic theory of collision, transition state theory of reaction rates, potential energy surfaces and reaction dynamics; diffusion; kinetics of unimolecular and bimolecular reactions; application of kinetics to biological systems. Catalysis: General catalytic mechanism (Arrhenius intermediate, Van’t Hoff intermediate), Acid-base catalysis, acidity function, Enzyme catalysis, Michealis-Menten equation, Inhibition, effects of pH, Bisubstrate reactions (sequential reaction, ping-pong reactions).
Text ReferenceTitle, Authors, Edition, Publisher, Year Since this course will be research-oriented, there is no official textbook other than original research papers and reviews identified by the instructor. Students will be responsible for downloading and printing PDFs. 1. B. Alberts, D. Bray, J. Levis, M. Raff, K. Roberts & J. D. Watson: Molecular Biology of the Cell; 5th Ed, Garland Science Fung, Y. C.: Biomechanics: Mechanical Properties of Living Tissues. 2nd Ed., Springer. 2. R. Kamm and M. K. Mofrad. Cytoskeletal Mechanics: Models and Measurements. Cambridge University Press.
DescriptionIntroduction to Mechanobiology Alterations of Tissue/Cell Properties in Diseases Extracellular Matrix (ECM) Composition Basics of Stress and Strain Rheological Characterization of Biopolymers Physical Properties of Collagen Gels Mechanosensitivity of Fibronectin Composition of Focal Adhesions Force Sensitivity of Focal adhesions Effect of ECM properties on Cell Adhesion, Cell Spreading and Cell Migration
Text ReferenceTitle, Authors, Edition, Publisher, Year 1.Blitterswijk CV, Tissue Engineering, Academic Press (2008). 2.Saltzman WM, Tissue Engineering, Oxford University Press (2004). 3.Lanza RP, Langer R, Vacanti JP, Principles of Tissue Engineering, Academic Press, 3rd Edition (2007). 4.Palsson B and Bhatia SN, Tissue Engineering, Pearson Prentice Hall (2004).
DescriptionThis course will cover introductory concepts in tissue engineering including basic cell culture techniques, methodology for preparation of scaffolds, natural and artificial biomaterials used for scaffolds, mechanisms of cell biomaterial interaction, cellular communication, biocompatibility and foreign body response, basic concepts governing cell survival and tissue organization, influence of environmental factors including mechanical loading and culture conditions (e.g. static versus dynamic), differentiated cell types and stem cells, regeneration of tissues and organs in vitro and in vivo. This knowledge will be applied to engineering of various body systems. Examples of tissue engineering based procedures employed clinically will be analyzed as case studies.

Semester III

Following courses will run in Sem III

Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Shuler, M. L., & Kargi, F. (2002). Bioprocess Engineering: Basic Concepts. Upper Saddle River, NJ: Prentice Hall. 2. Stanbury, P. F., & Whitaker, A. (2010). Principles of Fermentation Technology. Oxford: Pergamon Press. 3. Blanch, H. W., & Clark, D. S. (1997). Biochemical Engineering. New York: M. Dekker. 4. Bailey, J. E., & Ollis, D. F. (1986). Biochemical Engineering Fundamentals. New York: McGraw-Hill.
DescriptionIsolation, screening and maintenance of industrially important microbes; microbial growth and death kinetics (an example from each group, particularly with reference to industrially useful microorganisms); strain improvement for increased yield and other desirable characteristics. Elemental balance equations; metabolic coupling – ATP and NAD+; yield coefficients; unstructured models of microbial growth; structured models of microbial growth. Batch and continuous fermenters; modifying batch and continuous reactors: chemostat with recycle, multistage chemostat systems, fed-batch operations; conventional fermentation v/s biotransformation; immobilized cell systems; large scale animal and plant cell cultivation; fermentation economics; upstream processing: media formulation and optimization; sterilization; aeration, agitation and heat transfer in bioprocess; scale up and scale down; measurement and control of bioprocess parameters. Separation of insoluble products – filtration, centrifugation, sedimentation, flocculation; Cell disruption; separation of soluble products: liquid-liquid extraction, precipitation, chromatographic techniques, reverse osmosis, ultra and micro filtration, electrophoresis; final purification: drying; crystallization; storage and packaging. Isolation of micro-organisms of potential industrial interest; strain improvement; market analysis; equipment and plant costs; media; sterilization, heating and cooling; aeration and agitation; bath-process cycle times and continuous cultures; recovery costs; water usage and recycling; effluent treatment and disposal. Mechanism of enzyme function and reactions in process techniques; enzymatic bioconversions e.g. starch and sugar conversion processes; high-fructose corn syrup; interesterified fat; hydrolyzed protein etc. and their downstream processing; baking by amylases, deoxygenation and desugaring by glucoses oxidase, beer mashing and chill proofing; cheese making by proteases and various other enzyme catalytic actions in food processing. Fermented foods and beverages; food ingredients and additives prepared by fermentation and their purification; fermentation as a method of preparing and preserving foods; microbes and their use in pickling, producing colours and flavours, alcoholic beverages and other products; process wastes-whey, molasses, starch substrates and other food wastes for bioconversion to useful products; bacteriocins from lactic acid bacteria – production and applications in food preservation; biofuels and biorefinery
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Campbell, I. D. (2012). Biophysical Techniques. Oxford: Oxford University Press. 2. Serdyuk, I. N., Zaccai, N. R., & Zaccai, G. (2007). Methods in Molecular Biophysics: Structure, Dynamics, Function. Cambridge: Cambridge University Press. 3. Phillips, R., Kondev, J., & Theriot, J. (2009). Physical Biology of the Cell. New York: Garland Science. 4. Nelson, P. C., Radosavljević, M., & Bromberg, S. (2004). Biological Physics: Energy, Information, Life. New York: W.H. Freeman. 5. Huang, B., Bates, M., & Zhuang, X. (2009). Super-Resolution Fluorescence Microscopy. Annual Review of Biochemistry, 78(1), 993-1016. doi:10.1146/annurev. biochem.77.061906.092014. 6. Mohanraju, P., Makarova, K. S., Zetsche, B., Zhang, F., Koonin, E. V., & Oost, J. V. (2016). Diverse Evolutionary Roots and Mechanistic Variations of the CRISPR-Cas Systems. Science, 353(6299). doi:10.1126/science.aad5147. 7. Lander, E. (2016). The Heroes of CRISPR. Cell, 164(1-2), 18-28. doi:10.1016/j. cell.2015.12.041. 8. Ledford, H. (2016). The Unsung Heroes of CRISPR. Nature, 535(7612), 342-344. doi:10.1038/535342a. 9. Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science, 337(6096), 816-821. doi:10.1126/science.1225829. 10. Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hammers, C., Songa, E. B., Hammers, R. (1993). Naturally Occurring Antibodies Devoid of Light Chains. Nature, 363(6428), 446-448. doi:10.1038/363446a0. 11. Sidhu, S. S., & Koide, S. (2007). Phage Display for Engineering and Analyzing Protein Interaction Interfaces. Current Opinion in Structural Biology, 17(4), 481-487. doi:10.1016/j.sbi.2007.08.007. 12. Steyaert, J., & Kobilka, B. K. (2011). Nanobody Stabilization of G Protein-Coupled Receptor Conformational States. Current Opinion in Structural Biology, 21(4), 567-572. doi:10.1016/j.sbi.2011.06.011. 13. Vincke, C., & Muyldermans, S. (2012). Introduction to Heavy Chain Antibodies and Derived Nanobodies. Single Domain Antibodies, 15-26. doi:10.1007/978-1-61779- 968-6_2. 14. Verheesen, P., & Laeremans, T. (2012). Selection by Phage Display of Single Domain Antibodies Specific to Antigens in their Native Conformation. Single Domain Antibodies, 81-104. doi:10.1007/978-1-61779-968-6_6. 15. Li, J., Xia, L., Su, Y., Liu, H., Xia, X., Lu, Q. Reheman, K. (2012). Molecular Imprint of Enzyme Active Site by Camel Nanobodies. Journal of Biological Chemistry J. Biol. Chem., 287(17), 13713-13721. doi:10.1074/jbc.m111.336370. 16. Sohier, J., Laurent, C., Chevigné, A., Pardon, E., Srinivasan, V., Wernery, U. Galleni, M. (2013). Allosteric Inhibition of VIM Metallo-β-Lactamases by a Camelid Nanobody. Biochemical Journal, 450(3), 477-486. doi:10.1042/bj20121305. 17. Chakravarty, R., Goel, S., & Cai, W. (2014). Nanobody: The “Magic Bullet” for Molecular Imaging? Theranostics, 4(4), 386-398. doi:10.7150/thno.8006.
DescriptionBasic Microscopy: Light Microscopy: lenses and microscopes, resolution: Rayleigh’s Approach, Darkfield; Phase Contrast; Differential Interference Contrast; fluorescence and fluorescence microscopy: what is fluorescence, what makes a molecule fluorescent, fluorescence microscope; optical arrangement, light source; filter sets: excitation filter, dichroic mirror, and barrier, optical layout for image capture; CCD cameras; back illumination, binning; recording color; three CCD elements with dichroic beamsplitters, boosting the signal. Advanced Microscopy: Confocal microscope: scanning optical microscope, confocal principle, resolution and point spread function, light source: gas lasers & solid-state, primary beamsplitter; beam scanning, pinhole and signal channel configurations, detectors; pixels and voxels; contrast, spatial sampling: temporal sampling: signal-tonoise ratio, multichannel images. nonlinear microscopy: multiphoton microscopy; principles of two-photon fluorescence, advantages of two-photon excitation, tandem scanning (spinning disk) microscopes, deconvolving confocal images; image processing, three-dimensional reconstruction; advanced fluorescence techniques: FLIM, FRET, and FCS, Fluorescence Lifetime, Fluorescence Resonant Energy Transfer (FRET), Fluorescence Correlation Spectroscopy (FCS), Evanescent Wave Microscopy; Near-Field and Evanescent Waves, Total Internal Reflection Microscopy; Near-Field Microscopy; Beyond the Diffraction Limit: Stimulated Emission Depletion (STED), Super-Resolution Summary, Super-Resolution Imaging with Stochastic Optical Reconstruction Microscopy (STORM) and Photoactivated Localization Microscopy (PALM). Ionization techniques; mass analyzers/overview MS; FT-ICR and Orbitrap, fragmentation of peptides; proteomics, nano LC-MS; Phospho proteomics; interaction proteomics, mass spectroscopy in structural biology; imaging mass spectrometry. High throughput screens in cellular systems, target identification, validation of experimental methods to generate the omics data, bioinformatics analyses, mathematical modeling and designing testable predictions. X-ray diffraction methods, solution & solid-state NMR, cryo-electron microscopy, smallangle X-ray scattering, Atomic force microscopy. History of its discovery, elucidation of the mechanism including introduction to all the molecular players, development of applications for in vivo genome engineering for genetic studies, promise of the technology as a next generation therapeutic method. Introduction to nanobodies, combining nanobody with phage-display method for development of antibody against native proteins, nanobody as a tool for protein structure-function studies, use of nanobodies for molecular imaging, catabolic antibodies using nanobodies.
Text ReferenceN.A.
DescriptionStudents may be divided in groups and each group may be responsible for one classical paper. Each week there may be a 1.5 hour presentation cum discussion for each of the papers. At the end of the semester each student will be asked to write a mini-review (2-3 pages long) on any one classical paper, other than the one he/she presented/discussed. A list of sixteen classic papers and some suggested reference materials: Molecular Biology 1. Studies on the chemical nature of the substance inducing transformation of Pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III. Avery OT, Macleod CM, McCarty M.; J Exp Med. 1944 Feb 1;79(2):137-58. Note: This paper demonstrates that DNA is the transforming Principle originally described by Fredrick Griffith. 2. Independent functions of viral protein and nucleic acid in growth of bacteriophage Hershey AD and Chase M.; J Gen Physiol. 1952 May;36(1):39-56. Note: This paper demonstrates that DNA, and not protein, component of phages enter bacterial cells. 3. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid Watson JD and Crick FH; Nature. 1953 Apr 25;171(4356):737-8 Note: In this one page paper Watson and Crick first described the structure of DNA double helix Study help – Watson_Crick_Nature_1953_annotated 4. Transposable mating type genes in Saccharomyces cerevisiae James Hicks, Jeffrey N. Strathern & Amar J.S. Klar; Nature 282, 478-483,1979 Note: This paper provided evidence for ‘cassette hypothesis’ of yeast mating type switches i.e. interconversion of mating types in yeast (S. cerevisiae) occurs by DNA rearrangement. 5. Messelson & Stahl experiment demonstrating semi-conservative replication of DNA. Meselson M and Stahl FW.; Proc Natl Acad Sci U S A. 1958 Jul 15;44(7):671-82 Note: The experiment demonstrating semi-conservative mode of DNA replication is referred to as “the most beautiful experiment in biology” 6. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs Guo-Liang Yu, John D. Bradley, Laura D. Attardi & Elizabeth H. Blackburn; Nature 344, 126-132, 1990 Note: This paper demonstrates that the telomerase contains the template for telomere synthesis. Cell Biology 1. A protein-conducting channel in the endoplasmic reticulum Simon SM AND Blobel G.; Cell. 1991 May 3;65(3):371-80 Note: This paper demonstrates the existence of a protein conducting channel Study help – A brief history of Signal Hypothesis. 2. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway Novick P, Field C, Schekman R.; Cell. 1980 Aug;21(1):205-15 Note: In this groundbreaking paper Randy Schekman`s group used a mutagenesis screen for fast sedimenting yeast mutants to identify genes involved in cell secretion 3. A yeast mutant defective at an early stage in import of secretory protein precursors into the endoplasmic reticulum Deshaies RJ and Schekman R.; J Cell Biol. 1987 Aug;105(2):633-45 Note: Using another yeast mutation screen Schekman lab identifies Sec61, a component of ER protein Conducting Channel (PCC) Suggested reference paper – A biochemical assay for identification of PCC. 4. Reconstitution of the Transport of Protein between Successive Compartments of the Golgi Balch WE, Dunphy WG, Braell WA, Rothman JE.; Cell. 1984 Dec;39(2 Pt 1):405-16 Note: This paper describes setting up of an in vitro reconstituted system for transport between golgi stacks which eventually paved the way for identification of most of the molecular players involved in these steps including NSF, SNAP etc. 5. A complete immunoglobulin gene is created by somatic recombination Brack C, Hirama M, Lenhard-Schuller R, Tonegawa S.; Cell. 1978 Sep;15(1):1-14 Note: This study demonstrates DNA level molecular details of somatic rearrangement of immunoglobulin gene sequences leading to the generation of functionally competent antibody generating gene following recombination. 6. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition Buck L and Axel R; Cell. 1991 Apr 5;65(1):175-87 Note: This paper suggests that different chemical odorants associate with different cell-specific expression of a transmembrane receptor in Drosophila olfactory epithelium where a large family of odorat receptors is expressed. 7. Kinesin walks hand-over-hand Yildiz A, Tomishige M, Vale RD, Selvin PR.; Science. 2004 Jan 30;303(5658):676-8 Note: This paper shows that kinesin motor works as a two-headed dimeric motor walking hand-over-hand rather than like an inchworm on microtubule tract using the energy of ATP hydrolysis. Developmental Biology/ Genetics 1. Mutations affecting segment number and polarity in Drosophila Christiane Nusslein-Volhard and Eric Weischaus; Nature 287, 795-801, 1980 Note: This single mutagenesis screen identified majority of the developmentally important genes not only in flies but in other metazoans as well. 2. Information for the dorsal–ventral pattern of the Drosophila embryo is stored as maternal mRNA Anderson KV and Nüsslein-Volhard C; Nature. 1984 Sep 20-26;311(5983):223-7 Note: This landmark paper demonstrated that early dorsal-ventral pattern information is stored as maternal mRNA in flies and devised the method of identifying genes encoding such genes 3. Hedgehog signalling in the mouse requires intraflagellar transport proteins Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV.; Nature. 2003 Nov 6;426(6962):83-7 Note: One of the architects of original fly mutagenesis screens conducted a mouse mutagenes screen which identified a gene Kif3a as a major component of hedgehog signaling pathway. Eventually this discovery revolutionizes our understanding of mechanisms of action of signaling pathways by demonstrating central role of cillia in it. Suggested Reference paper – Design and execution of a embryonic lethal mutation screen in mouse.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Adams, D. J., & Sparrow, J. C. (2008). Enterprise for Life Scientists: Developing Innovation and Entrepreneurship in the Biosciences. Bloxham: Scion. 2. Shimasaki, C. D. (2014). Biotechnology Entrepreneurship: Starting, Managing, and Leading Biotech Companies. Amsterdam: Elsevier. Academic Press is an imprint of Elsevier. 3. Onetti, A., & Zucchella, A. Business Modeling for Life Science and Biotech Companies: Creating Value and Competitive Advantage with the Milestone Bridge. Routledge. 4. Jordan, J. F. (2014). Innovation, Commercialization, and Start-Ups in Life Sciences. London: CRC Press. 5. Desai, V. (2009). The Dynamics of Entrepreneurial Development and Management. New Delhi: Himalaya Pub. House.
DescriptionIntroduction and scope in Bio-entrepreneurship, Types of bio-industries and competitive dynamics between the sub-industries of the bio-sector (e.g. pharmaceuticals vs. Industrial biotech), Strategy and operations of bio-sector firms: Factors shaping opportunities for innovation and entrepreneurship in bio-sectors, and the business implications of those opportunities, Alternatives faced by emerging bio-firms and the relevant tools for strategic decision, Entrepreneurship development programs of public and private agencies (MSME, DBT, BIRAC, Make In India), strategic dimensions of patenting & commercialization strategies. Negotiating the road from lab to the market (strategies and processes of negotiation with financiers, government and regulatory authorities), Pricing strategy, Challenges in marketing in bio business (market conditions & segments; developing distribution channels, the nature, analysis and management of customer needs), Basic contract principles, different types of agreement and contract terms typically found in joint venture and development agreements, Dispute resolution skills. Business plan preparation including statutory and legal requirements, Business feasibility study, financial management issues of procurement of capital and management of costs, Collaborations & partnership, Information technology. Technology – assessment, development & upgradation, Managing technology transfer, Quality control & transfer of foreign technologies, Knowledge centers and Technology transfer agencies, Understanding of regulatory compliances and procedures (CDSCO, NBA, GCP, GLA, GMP).
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Ganguli, P. (2001). Intellectual Property Rights: Unleashing the Knowledge Economy. New Delhi: Tata McGraw-Hill Pub. 2. National IPR Policy, Department of Industrial Policy & Promotion, Ministry of Commerce, GoI 3. Complete Reference to Intellectual Property Rights Laws. (2007). Snow White Publication Oct. 4. Kuhse, H. (2010). Bioethics: an Anthology. Malden, MA: Blackwell. 5. Office of the Controller General of Patents, Design & Trademarks; Department of Industrial Policy & Promotion; Ministry of Commerce & Industry; Government of India. http://www.ipindia.nic.in/ 6. Karen F. Greif and Jon F. Merz, Current Controversies in the Biological Sciences -Case Studies of Policy Challenges from New Technologies, MIT Press 7. World Trade Organisation. http://www.wto.org 8. World Intellectual Property Organisation. http://www.wipo.int 9. International Union for the Protection of New Varieties of Plants. http://www.upov.int 10. National Portal of India. http://www.archive.india.gov.in 11. National Biodiversity Authority. http://www.nbaindia.org 12. Recombinant DNA Safety Guidelines, 1990 Department of Biotechnology, Ministry of Science and Technology, Govt. of India. Retrieved from http://www.envfor.nic.in/ divisions/csurv/geac/annex-5.pdf 13. Wolt, J. D., Keese, P., Raybould, A., Fitzpatrick, J. W., Burachik, M., Gray, A., Wu, F. (2009). Problem Formulation in the Environmental Risk Assessment for Genetically Modified Plants. Transgenic Research, 19(3), 425-436. doi:10.1007/s11248-009-9321-9 14. Craig, W., Tepfer, M., Degrassi, G., & Ripandelli, D. (2008). An Overview of General Features of Risk Assessments of Genetically Modified Crops. Euphytica, 164(3), 853-880. doi:10.1007/s10681-007-9643-8 15. Guidelines for Safety Assessment of Foods Derived from Genetically Engineered Plants. 2008. 16. Guidelines and Standard Operating Procedures for Confined Field Trials of Regulated Genetically Engineered Plants. 2008. Retrieved from http://www.igmoris.nic.in/guidelines1.asp 17. Alonso, G. M. (2013). Safety Assessment of Food and Feed Derived from GM Crops: Using Problem Formulation to Ensure “Fit for Purpose” Risk Assessments. Retrieved from http://biosafety.icgeb.org/inhousepublicationscollectionbiosafetyreviews.
DescriptionIntroduction to intellectual property; types of IP: patents, trademarks, copyright & related rights, industrial design, traditional knowledge, geographical indications, protection of new GMOs; International framework for the protection of IP; IP as a factor in R&D; IPs of relevance to biotechnology and few case studies; introduction to history of GATT, WTO, WIPO and TRIPS; plant variety protection and farmers rights act; concept of ‘prior art’: invention in context of “prior art”; patent databases – country-wise patent searches (USPTO, EPO, India); analysis and report formation. Basics of patents: types of patents; Indian Patent Act 1970; recent amendments; WIPO Treaties; Budapest Treaty; Patent Cooperation Treaty (PCT) and implications; procedure for filing a PCT application; role of a Country Patent Office; filing of a patent application; precautions before patenting-disclosure/non-disclosure – patent application- forms and guidelines including those of National Bio-diversity Authority (NBA) and other regulatory bodies, fee structure, time frames; types of patent applications: provisional and complete specifications; PCT and conventional patent applications; international patenting-requirement, procedures and costs; financial assistance for patenting-introduction to existing schemes; publication of patents-gazette of India, status in Europe and US; patent infringement- meaning, scope, litigation, case studies and examples; commercialization of patented innovations; licensing – outright sale, licensing, royalty; patenting by research students and scientists- university/organizational rules in India and abroad, collaborative research – backward and forward IP; benefit/credit sharing among parties/community, commercial (financial) and non- commercial incentives. Biosafety and Biosecurity – introduction; historical background; introduction to biological safety cabinets; primary containment for biohazards; biosafety levels; GRAS organisms, biosafety levels of specific microorganisms; recommended biosafety levels for infectious agents and infected animals; definition of GMOs & LMOs; principles of safety assessment of transgenic plants – sequential steps in risk assessment; concepts of familiarity and substantial equivalence; risk – environmental risk assessment and food and feed safety assessment; problem formulation – protection goals, compilation of relevant information, risk characterization and development of analysis plan; risk assessment of transgenic crops vs cisgenic plants or products derived from RNAi, genome editing tools. International regulations – Cartagena protocol, OECD consensus documents and Codex Alimentarius; Indian regulations – EPA act and rules, guidance documents, regulatory framework – RCGM, GEAC, IBSC and other regulatory bodies; Draft bill of Biotechnology Regulatory authority of India – containments – biosafety levels and category of rDNA experiments; field trails – biosafety research trials – standard operating procedures – guidelines of state governments; GM labeling – Food Safety and Standards Authority of India (FSSAI). Introduction, ethical conflicts in biological sciences – interference with nature, bioethics in health care – patient confidentiality, informed consent, euthanasia, artificial reproductive technologies, prenatal diagnosis, genetic screening, gene therapy, transplantation. Bioethics in research – cloning and stem cell research, Human and animal experimentation, animal rights/welfare, Agricultural biotechnology – Genetically engineered food, environmental risk, labeling and public opinion. Sharing benefits and protecting future generations – Protection of environment and biodiversity – biopiracy
Text ReferenceN.A.
DescriptionSelection of research lab and research topic: Students should first select a lab wherein they would like to pursue their dissertation. The supervisor or senior researchers should be able to help the students to read papers in the areas of interest of the lab and help them select a topic for their project. The topic of the research should be hypothesis driven. Review of literature: Students should engage in systematic and critical review of appropriate and relevant information sources and appropriately apply qualitative and/or quantitative evaluation processes to original data; keeping in mind ethical standards of conduct in the collection and evaluation of data and other resources. Writing Research Proposal: With the help of the senior researchers, students should be able to discuss the research questions, goals, approach, methodology, data collection, etc. Students should be able to construct a logical outline for the project including analysis steps and expected outcomes and prepare a complete proposal in scientific proposal format for dissertation. Poster Presentation Students will have to present the topic of their project proposal after few months of their selection of the topic. They should be able to explain the novelty and importance of their research topic. Oral Presentation At the end of their project, presentation will have to be given by the students to explain work done by them in detail. Along with summarizing their findings they should also be able to discuss the future expected outcome of their work.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Shuler, M. L., & Kargi, F. (2002). Bioprocess Engineering: Basic Concepts. Upper Saddle River, NJ: Prentice Hall. 2. Stanbury, P. F., & Whitaker, A. (2010). Principles of Fermentation Technology. Oxford: Pergamon Press. 3. Blanch, H. W., & Clark, D. S. (1997). Biochemical Engineering. New York: M. Dekker. 4. Bailey, J. E., & Ollis, D. F. (1986). Biochemical Engineering Fundamentals. New York: McGraw-Hill. 5. El-Mansi, M., & Bryce, C. F. (2007). Fermentation Microbiology and Biotechnology. Boca Raton: CRC/Taylor & Francis.
Description1. Basic Microbiology techniques a) Scale up from frozen vial to agar plate to shake flask culture. b) Instrumentation: Microplate reader, spectrophotometer, microscopy. c) Isolation of microorganisms from soil samples. 2. Experimental set-up a) Assembly of bioreactor and sterilization. b) Growth kinetics. c) Substrate and product inhibitions. d) Measurement of residual substrates. 3. Data Analysis a) Introduction to Metabolic Flux Analysis (MFA). 4. Fermentation a) Batch. b) Fed-batch. c) Continuous. 5. Unit operations a) Microfiltrations: Separation of cells from broth. b) Bioseparations: Various chromatographic techniques and extractions. 6. Bioanalytics a) Analytical techniques like HPLC, FPLC, GC, GC-MS etc. for measurement of amounts of products/substrates.
Text Reference1. Bioinformatics. Keith, J. Humana Press, 2008. 2. Computer methods for macromolecular sequence analysis. R.F. Doolittle, Academic Press, 1996. 3. Bioinformatics. Sequence and genome analysis. D.W.Mount. Cold Spring Harbor Lab. press. 2004. 4. Bioinformatics and functional genomics. J. Pevsner. Wiley-Liss, 2003. 5. Encyclopedia of Genetics, Genomics, Proteomics & Bioinformatics, Jorde et al., (eds.) John Wiley and Sons, 2005.
DescriptionProtein modelling: Introduction; force field methods; energy, buried and exposed residues; side chains and neighbours; fixed regions; hydrogen bonds; mapping properties onto surfaces; fitting monomers; RMS fit of conformers; assigning secondary structures; Protein structure completion: backbone construction and side chain addition; small peptide methodology; software accessibility; building peptides; protein displays; substructure manipulations, annealing. Protein structure prediction: (i) Folding and model generation: secondary structure prediction; analyzing secondary structures; protein loop searching; loop generating methods. (ii) Homology modelling: potential applications, description, methodology, homologous sequence identification; align structures, align model sequence; construction of variable and conserved regions; sequence-based methods of structure prediction. (iii) Threading techniques; topology fingerprint approach for prediction; evaluation of alternate models; structure prediction on a mystery sequence; structure aided sequence techniques of structure prediction; (iv) Structural profiles, alignment algorithms, mutation tables, prediction, validation. (v) Fold prediction; prediction using inverse folding, significance analysis, scoring techniques, sequence-sequence scoring; Protein function prediction; Elements of in silico drug design: Molecular docking, drug library, protein-ligand structure analysis, ligand modeling Using RNA structure prediction tools.

Elective II

Elective II

Elective II courses

Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Krogsgaard-Larsen et al. Textbook of Drug Design and Discovery. 4th Edition. CRC Press. 2. Kuhse, H. (2010). Bioethics: an Anthology. Malden, MA: Blackwell. 3. Nally, J. D. (2006) GMP for Pharmaceuticals. 6th edition. CRC Press 4. Brody, T. (2016) Clinical Trials: Study Design, Endpoints and Biomarkers, Drug Safety, and FDA and ICH Guidelines. Academic Press.
DescriptionIdentification of target or drug leads associated with a particular disease by a number of different techniques including combinations of molecular modeling, combinatorial libraries and high-throughput screening (HTS); Conceptualizing the automation of the HTS process and the importance of bioinformatics and data processing in identification of lead compounds; Rational drug design, based on understanding the three-dimensional structures and physicochemical properties of drugs and receptors; Modelling drug/ receptor interactions with the emphasis on molecular mechanisms, molecular dynamics simulations and homology modelling; Conformational sampling, macromolecular folding, structural bioinformatics, receptor-based and ligand-based design and docking methods, in silico screening of libraries, semi-empirical and ab-initio methods, QSAR methods, molecular diversity, design of combinatorial libraries of drug-like molecules, macromolecular and chemical databases. Identification of relevant groups on a molecule that interact with a receptor and are responsible for biological activity; Understanding structure activity relationship; Structure modification to increase potency and therapeutic index; Concept of quantitative drug design using Quantitative structure–activity relationship models (QSAR models) based on the fact that the biological properties of a compound are a function of its physicochemical parameters such as solubility, lipophilicity, electronic effects, ionization, stereochemistry, etc.; Bioanalytical assay development in support of in vitro and in vivo studies (LC/MS/MS, GC/MS and ELISA). Principles of drug absorption, drug metabolism and distribution – intestinal absorption, metabolic stability, drug-drug interactions, plasma protein binding assays, metabolite profile studies, Principles of toxicology, Experimental design for preclinical and clinical PK/PD/TK studies, Selection of animal model; Regulatory guidelines for preclinical PK/ PD/TK studies; Scope of GLP, SOP for conduct of clinical & non clinical testing, control on animal house, report preparation and documentation Integration of non-clinical and preclinical data to aid design of clinical studies. Requirements of GMP implementation, Documentation of GMP practices, CoA, Regulatory certification of GMP, Quality control and Quality assurance, concept and philosophy of TQM, ICH and ISO 9000; ICH guidelines for Manufacturing, Understanding Impurity Qualification Data, Stability Studies. Objectives of Phase I, II, III and IV clinical studies, Clinical study design, enrollment, sites and documentation, Clinical safety studies: Adverse events and adverse drug reactions, Clinical PK, pharmacology, drug-drug interaction studies, Statistical analysis and documentation. Global Regulatory Affairs and different steps involved, Regulatory Objectives, Regulatory Agencies; FDA guidelines on IND and NDA submissions, Studies required for IND and NDA submissions for oncology, HIV, cardiovascular indications, On-label vs. off-label drug use GCP and Requirements of GCP Compliance, Ethical issues and Compliance to current ethical guidelines, Ethical Committees and their set up, Animal Ethical issues and compliance.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Evolution: Making sense of life, Carl Zimmer, Douglas J. Emlen, 2nd Edition, W. H. Freeman, 2016 2. Strickberger`s Evolution. Brian K. Hall & Bendikt Hallgrimsson, Jones and Bartlett Publishers, 4th edition, 2007. 3. Selected research articles
DescriptionWhat is evolution? Introduction and historical perspectives, major questions in evolutionary biology, drift and selection, mechanisms of natural selection, artificial selection, concept of fitness, microevolution, macroevolution—speciation and extinction.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. H. J. Rehm, G. Reed and H. Pape (Eds.); Biotechnology: A Comprehensive Treatise in eight volumes. VCH, 1986. 2. M. Moo-Young (Eds.); Comprehensive Biotechnology (3 Vols.). Elsevier, London 1986. 3. Selected reviews and articles from Nature, Science, Annual reviews etc.
DescriptionThis course covers three to four contemporary themes in Biotechnology from among: Plant cell culture and tissue culture; Enzymes and Biocatalyses- immobilized enzyme applications; Bioconversion/fermentation of industrial fine chemicals; Antibiotics and chemotherapy; Recombinant DNA technology and protein therapeutics; Waste treatment, Utilization and methanogenesis.
Text ReferenceAidley DJ The physiology of excitable cells, Cambridge University Press, 3rd Edn, 1989, & 4th Ed, 1998. Brown AG Nerve Cells and Nervous Systems, Narosa, 1991. Kuffler SJ, Nicholls J, Martin AR From Neuron to Brain, 3rd Ed, Sinauer, 1992. Also 4th Ed., 2002. Kandel E, Schwartz K Principles of Neural Science, 5th Ed, Elsevier, 2012. Also 4th Ed, 2000, 3nd Ed, 1995. Barr R, Plonsey RL Bioelectricity: a quantitative approach, Plenum, 1988. Also 3rd Edn, 2007. Plonsey, RL & Malmivuo Bioelectromagnetism, OUP, New York, 1995 Also Plonsey, R Bioelectric Phenomena, Academic Press, 1969. Johnston D. and Wu S. Foundations Of Cellular Neurophysiology, MIT Press, 1995.
DescriptionOrigin of cellular potentials: resting membrane potential; Nernst equation and Nernst potentials. Selective permeability; Goldman-Hodgkin-Katz equation. Action potentials: ionic basis, properties of generation and conduction, examples in different cell types. Voltage Clamp technique and experiments. Hodgkin-Huxley model for active conductances and action potential. Axons and muscle cells as transmission-line cables; introduction to cable theory. Cable equation and its implications for action potential properties. Neurotransmission, synaptic potentials and synaptic integration: application of GHK equation and cable theory. Clinical implications of topics covered. Paper discussion(s).
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. GeroDecher, Joseph B. Schlenoff, (2003); Multilayer Thin Films: Sequential Assembly of Nanocomposite Materials, Wiley-VCH Verlag GmbH & Co. KGaA 2. David S. Goodsell, (2004); Bionanotechnology: Lessons from Nature; Wiley-Liss 3. Neelina H. Malsch (2005), Biomedical Nanotechnology, CRC Press 4. Greg T. Hermanson, (2013); Bioconjugate Techniques, (3rd Edition); Elsevier 5. Recent review papers in the area of Nanomedicine.
DescriptionIntroduction to Nanobiotechnology; Concepts, historical perspective; Different formats of nanomaterials and applications with example for specific cases; Cellular Nanostructures; Nanopores; Biomolecular motors; Bio-inspired Nanostructures, Synthesis and characterization of different nanomaterials. Thin films; Colloidal nanostructures; Self Assembly, Nanovesicles; Nanospheres; Nanocapsules and their characterisation. Nanoparticles for drug delivery, concepts, optimization of nanoparticle properties for suitability of administration through various routes of delivery, advantages, strategies for cellular internalization and long circulation, strategies for enhanced permeation through various anatomical barriers. Nanoparticles for diagnostics and imaging (theranostics); concepts of smart stimuli responsive nanoparticles, implications in cancer therapy, nanodevices for biosensor development. Nanomaterials for catalysis, development and characterization of nanobiocatalysts, application of nanoscaffolds in sythesis, applications of nanobiocatalysis in the production of drugs and drug intermediates. Introduction to Safety of nanomaterials, Basics of nanotoxicity, Models and assays for Nanotoxicity assessment; Fate of nanomaterials in different stratas of environment; Ecotoxicity models and assays; Life Cycle Assessment, containment.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Rajagopal Vadivambal, Digvir S. Jayas. (2015). Bio-Imaging: Principles, Techniques, and Applications. ISBN 9781466593671 – CAT# K20618. 2. Alberto Diaspro, Marc A. M. J. van Zandvoort. (2016). Super-Resolution Imaging in Biomedicine. ISBN 9781482244342 – CAT# K23483. 3. Taatjes, Douglas, Roth, Jürgen (Eds.). (2012). Cell Imaging Techniques Methods and Protocols. ISBN 978-1-62703-056-4.
DescriptionOne of the most basic techniques for live-cell imaging is widefield fluorescent microscopy. Standard inverted research grade microscopes can yield valuable results if you are imaging adherent cells, large regions of interest (such as organelles) or very thin tissue sections (less than 5 micrometer). In widefield, a CCD camera is usually used to capture images and the epi- fluorescence illumination source can be a mercury lamp, xenon lamp, LED’s, etc. Each of light sources require carefully matched interference filters for specific excitation and emission wavelengths of your fluorophore of interest. With widefield microscopy, your specimen is only exposed to excitation light for relatively short time periods as the full aperture of emission light is collected by the objectives. Widefield fluorescence microscopy can be used in combination with other common contrast techniques such as phase contrast and differential interference contract (DIC) microscopy. This combination is useful when performing live-cell imaging to examine general cell morphology or viability while also imaging regions of interest within cells. CLSM has ability to eliminate out-of-focus light and information. It is also possible to obtain optical serial sections from thicker specimens. A conjugate pinhole in optical path of confocal microscope prevents fluorescence from outside of focal plane from being collected by photomultiplier detector or imaged by camera. In CLSM, a single pinhole (and single focused laser spot) is scanned across specimen by scanning system. This spot forms a reflected epi- fluorescence image back on original pinhole. When specimen is in focus, fluorescent light from it passes through pinhole to detector. Any out-of-focus light is defocused at pinhole and very little of this signal passes through to detector meaning that background fluorescence is greatly reduced. The pinhole acts as a spatial filter for emission light from the specimen. This method utilises a ‘Nipkow Disc’ which is a mechanical opaque disc which has a series of thousands of drilled or etched pinholes arranged in a spiral pattern. Each illuminated pinhole on disc is imaged by microscope objective to a diffraction-limited spot on region of interest on specimen. The emission from fluorophores passes back though Nipkow disc pinholes and can be observed and captured by a CCD camera. The effect of spinning disc is that many thousands of points on specimen are simultaneously illuminated. Using SDCM to examine a specimen means that real-time imaging (30-frames-per-second or faster) can be achieved, which is extremely useful if you are looking at dynamic changes within living cells over a wide spectrum of time-scales. This method enables one to perform live-cell imaging on whole embryos, tissues and cell spheroids in vivo in a gentle manner with high temporal resolution and in three dimensions. One is able to track cell movement over extended periods of time and follow development of organs and tissues on a cellular level. The next evolution of light-sheet fluorescence microscopy, termed lattice light-sheet microscopy as developed by Eric Betzig (Nobel Prize Laureate 2014 for PALM super-resolution microscopy) will even allow live-cell imaging with super-resolved in vivo cellular localization capabilities. Super-Resolution in a Standard Microscope: From Fast Fluorescence Imaging to Molecular Diffusion Laws in Live Cells; Photoswitching Fluorophores in Super-Resolution Fluorescence Microscopy; Image Analysis for Single-Molecule Localization Microscopy Deconvolution of Nanoscopic Images; Super-Resolution Fluorescence Microscopy of the Nanoscale Organization in cells; Correlative Live-Cell and Super-Resolution Microscopy and Its Biological Applications; SAX Microscopy and Its Application to Imaging of 3D-Cultured Cells; Quantitative Super-Resolution Microscopy for Cancer Biology and Medicine. Structured Illumination Microscopy; Correlative Nanoscopy: AFM Super-Resolution (STED/STORM) ; Stochastic Optical Fluctuation Imaging.
Text Reference

1. Saltzman WM, Engineering Principles for Drug Therapy, Oxford University Press (2001).
2. Wang B, Siahaan T, Soltero R, Drug delivery principles and applications, Wiley-Interscience, (2005).

DescriptionFundamentals of drug delivery, including physiology, pharmacokinetics, drug diffusion and permeation through biological barriers; Various types of drug and gene delivery routes including oral, transdermal, implantable, targeted and pulmonary; Controlled drug delivery, biomaterials used in drug delivery, particle targeting via receptor-ligand interactions, intracellular transport of collodial particles, protein and peptide delivery, synthetic gene delivery vectors; Case studies of current pharmaceutical products.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Immunobiology: the immune system in health and disease, 8th edition by C A Janeway, Garland Publishing company, 2014. 2. Immunology. 6th edition by Janes Kuby; W.H. Freeman and Company New york (2014). 3. Cellular and Molecular Immunology. 8th ed. A K Abbas, A H Lichtman, J S Pober, W B Saunders Company, 2014.
DescriptionGeneration of immune responses: overview, component of immune system, T cell activation, dendritic cell activation and licensing, T cells and DCs interaction, T cells: effector T cells, CTLs and their differentiation and roles in different diseases, Allergy and Autoimmune disorder: overview and diseases pathology and roles of immune system in pathogenesis of allergy and autoimmune disorders, Cancer immunology: roles of immune responses in cancer prevention, overview of current and investigational immunotherapy. Immunodiagnostics: flowcytometry, ELISA and multiplex assay, assay development.

Semester IV

Sem IV courses

Text ReferenceN.A.
DescriptionBased on the project proposal submitted in earlier semester, students should be able to plan, and engage in, an independent and sustained critical investigation and evaluate a chosen research topic relevant to biological sciences and society. They should be able to systematically identify relevant theory and concepts, relate these to appropriate methodologies and evidence, apply appropriate techniques and draw appropriate conclusions. Senior researchers should be able to train the students such that they can work independently and are able to understand the aim of each experiment performed by them. They should also be able to understand the possible outcomes of each experiment. At the end of their project, thesis has to be written giving all the details such as aim, methodology, results, discussion and future work related to their project. Students may aim to get their research findings published in a peer-reviewed journal. If the research findings have application-oriented outcomes, the students may file patent application.

Environmental Studies
(ES200 + HS200)

Elective III

Elective III

Elective III courses

Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Lee, Y. K. (2013). Microbial Biotechnology: Principles and Applications. Hackensack, NJ: World Scientific. 2. Moo-Young, M. (2011). Comprehensive Biotechnology. Amsterdam: Elsevier. 3. Nelson, K. E. (2015). Encyclopedia of Metagenomics. Genes, Genomes and Metagenomes: Basics, Methods, Databases and Tools. Boston, MA: Springer US. 4. The New Science of Metagenomics Revealing the Secrets of Our Microbial Planet. (2007). Washington, D.C.: National Academies Press. 5. Journals: (a) Nature, (b) Nature Biotechnology, (c) Applied microbiology and biotechnology, (d) Trends in Biotechnology, (e) Trends in Microbiology, (f) Current opinion in Microbiology, (g) Biotechnology Advances, (h) Genome Research) 6. Websites: http://jgi.doe.gov/our-science/
DescriptionMicrobial technology in human welfare; Isolation and screening of microbes important for industry – advances in methodology and its application; Advanced genome and epigenome editing tools (e.g., engineered zinc finger proteins, TALEs/TALENs, and the CRISPR/Cas9 system as nucleases for genome editing, transcription factors for epigenome editing, and other emerging tools) for manipulation of useful microbes/ strains and their applications; Strain improvement to increase yield of selected molecules, e.g., antibiotics, enzymes, biofuels. Environmental application of microbes; Ore leaching; Biodegradation – biomass recycle and removal; Bioremediation – toxic waste removal and soil remediation; Global Biogeochemical cycles; Environment sensing (sensor organisms/ biological sensors); International and National guidelines regarding use of genetically modified organisms in environment, food and pharmaceuticals. Recombinant protein and pharmaceuticals production in microbes – common bottlenecks and issues (technical/operational, commercial and ethical); Attributes required in industrial microbes (Streptomyces sp., Yeast) to be used as efficient cloning and expression hosts (biologicals production); Generating diversity and introduction of desirable properties in industrially important microbes (Streptomyces/Yeast); Microbial cell factories; Downstream processing approaches used in industrial production process (Streptomyces sp., Yeast). Application of microbes and microbial processes in food and healthcare industries – food processing and food preservation, antibiotics and enzymes production, microbes in targeted delivery application – drugs and vaccines (bacterial and viral vectors); Nonrecombinant ways of introducing desirable properties in Generally recognized as safe (GRAS) microbes to be used in food (e.g., Yeast) – exploiting the existing natural diversity or the artificially introduced diversity through conventional acceptable techniques (mutagenesis, protoplast fusion, breeding, genome shuffling, directed evolution etc.). Microbial genomics for discovery of novel enzymes, drugs/ antibiotics; Limits of microbial genomics with respect to use in human welfare; Metagenomics and metatranscriptomics – their potential, methods to study and applications/use (animal and plant health, environmental clean- up, global nutrient cycles & global sustainability, understanding evolution), Global metagenomics initiative – surveys/projects and outcome, metagenomic library construction and functional screening in suitable hosts – tools and techniques for discovery/identification of novel enzymes, drugs (e.g., protease, antibiotic) etc.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Cell Biology, T.D. Pollard and WC Earnshaw, SAUNDERS, 2002. 2. Biochemistry, L. Stryer, 4th Edition, W.H. Freeman and Company, New York, 1995 3. Fundamentals of Biochemistry. Life at the molecular level. D.J.Voet & J.G.Voet. 3rd edition, Wiley. 2008. 4. Proteins: Structures and Molecular Properties, T. E. Creighton, W. H. Freeman; Second Edition, 1992 5. Introduction to Protein Structure; Carl Branden, John Tooze, Garland Science; 2nd edition, (January 1, 1999)
DescriptionProteins: Protein structural levels (primary, secondary, tertiary, quaternary, quinary), Ramchandran’s plot, types of protein fold, physical parameters that govern protein-folding, forces that stabilizes protein structure, De novo protein design, Structure-function relationship of proteins, Expression and purification of protein, protein folding in vitro, role of osmolytes in protein folding, protein biosynthesis, In-vivo protein folding, role of chaperones in protein folding, post translation modification of proteins and their roles in protein structure and functions, mechanisms of protein degradation, protein self-assembly for biological functions, description of fibrous proteins, protein misfolding and aggregation, ER folding diseases, lysosomal biogenesis, lysosomal storage diseases, amyloid and neurodegenerative diseases, Directed Evolution
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Structural Biology Particle NMR applications by Quincy Teng Springer 2. NMR of proteins and Nucleic acids 1st Edition by K. Wuthrich 3. Protein NMR spectroscopy edited by John Cavanagh 2nd edition 4. “Biomolecular Crystallography: Principles, Practice, and Application to Structural Biology; by Bernhard Rupp: Garland Science, Taylor & Francis Group LLC., 1st edition, 2010. 5. Crystallography Made Crystal Clear: A Guide for Users of Macromolecular Models; by Gale Rhodes: Elsevier Inc., 3rd edition, 2006. 6. Principles of Protein X-Ray Crystallography; by Jan Drenth: Springer Science + Business Media LLC., 3rd edition, 2007. 7. Three-Dimensional Electron Microscopy of Macromolecular Assemblies: Visualization of Biological Molecules in Their Native State, 2nd Edition, (2006) Joachim Frank, Oxford University Press. 8. Computational Methods for Three-Dimensional Microscopy Reconstruction, (2014), Gabor T. Herman and Joachim Frank, Springer. 9. Cheng, Yifan et al. “A primer to single-particle cryo-electron microscopy.” Cell vol. 161,3 (2015): 438-449.
DescriptionStructural Biology by NMR spectroscopy: Basic principle of NMR, NMR instrumentation, NMR sample preparation, particle aspects of data acquisition, Multi-dimensional NMR, protein structure determination from NMR data, Protein-protein interactions and Protein-ligand interaction by NMR, Practice session: Setting on 2D experiments on peptide and data analysis. Protein crystallography: Protein crystallization, Crystal geometry, X-ray diffraction, Instrumentation and diffraction data collection, Diffraction data to electron density, Solving phase problem, Isomorphous replacement method, Molecular replacement method, Model building and refinement, Structure validation and deposition; Practice sessions: (1) Protein Crystallization, (ii) Diffraction data collection and (iii) Structure solution and refinement Cryo-EM for structure determination of biological molecules: Syllabus: Basics of Electron Microscopy, direct detector camera, Image formation, Contrast Transfer Function, Dose limitation, Data Collections Strategies, 2D to 3D reconstruction, resolution assessment, cryo- EM map interpretation and modelling, Practical/ hands on experience Session: Sample preparation with room temperature and freezing methods, docking into cryo-EM map and modelling
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Enzymatic reaction mechanisms by C. Walsh. WH Freeman, San Francisco (1979). 2. Enzyme Kinetics by I. Segel. Wiley Interscience, NewYork (1993). 3. An introduction to enzyme and coenzyme chemistry by T. Bugg 2nd Ed., Blackwell Publishers, Oxford (2004). 4. Enzyme Kinetics: Principles and Methods by H. Bisswanger Translated by L. Bubenheim. 5. Wiley-VCH Verlag GmbH, Weinheim, Germany (2002). 6. Fundamentals of Enzyme Kinetics by A. Cornish-Bowden 3rd Edition, Portland Press, London (2004).
DescriptionRate accelerations in biological systems; Catalysis and historical perspective on enzymes; Overview of applied enzymology and enzyme technology; Enzyme nomenclature; Origins of enzyme catalytic power; Structural basis of enzyme action and characterization of active site residues; Kinetic approaches to understand enzyme action; Michaelis-Menten kinetics; Evaluation of Km, kcat and enzyme inhibition analysis; Concept of an efficient catalyst; Elucidation of kinetic mechanism through initial velocity, product inhibition, pH and isotopic analysis; Role of metal ions in enzyme catalysis; Integration of kinetic, chemical and structural data to describe enzyme action; Control of enzyme activity and its role in regulating metabolism – in vivo enzymology; Frontiers in enzymology: Rational design of an enzyme catalyst, directed evolution, abzymes, non-protein catalysts.
Text ReferenceTitle, Authors, Edition, Publisher, Year 1. Physical Biology of the Cell, R Phillips, J Kondev, J. Theriot, Garland Science (2009). 2.A Course in Mathematical Biology: Quantitative Modeling with Mathematical and Computational Methods, Gerda de Vries, Thomas Hillen, Mark Lewis, BirgittSchõnfisch, Johannes Muller, SIAM (2006) 3.Dynamic Models in Biology, Stephen P. Ellner, John Guckenheimer,Princeton University Press (2006)
DescriptionExamples of simple models to understand different types of biological processes such as Lotka- Voltera model, simple epidemic model, reaction-diffusion models, drift-diffusion models and many more. Introductions to stochastic processes in biology, Introduction to Fokker-Planck and Langevin equations. Introduction to computer simulations. Introductions to different types of simulations-Molecular Dynamics, Monte Carlo and Langevin dynamics simulations. Simple examples of application of direct Monte Carlo simulation and Gillespie algorithm to a number of simple stochastic biological systems.
Text Reference1.302223Biomolecular Crystallography: Principles, Practice, and Application to Structural Biology302224 by Bernhard Rupp: Garland Science, Taylor & Francis Group LLC., 1st edition, 2010.2.302223Crystallography Made Crystal Clear: A Guide for Users of Macromolecular Models302224 by Gale Rhodes: Elsevier Inc., 3rd edition, 2006.3.302223Principles of Protein X-Ray Crystallography302224 by Jan Drenth: Springer Science + Business Media LLC., 3rd edition, 2007.
DescriptionIntroduction about the course, Brief introduction about protein structure, Protein production for crystallization, Protein crystallization, Crystal geometry, X-ray diffraction, Statistics and probability in crystallography, Instrumentation and diffraction data collection, Diffraction data to electron density, Solving phase problem, Isomorphous replacement method, Anomalous scattering method, Phase combination and improvement, Molecular replacement, Model building and refinement, Structure validation and deposition, Judging a crystallographic model, Computer program for analyzing protein structures, Tutorials, Structure analysis.
Text Reference1. Levitt M.H., Spin Dynamics: Basics of Nuclear Magnetic Resonance2. 4. Kurt W303274thrichNMR of proteins and nucleic acids3. Cavanagh John, Fairbrother Wayne J., Palmer IIIArthur G., Skelton Nicholas J., Editors,Protein NMR Spectroscopy: Principles and Practice,4. Chary KVR, Govil G.NMR in Biological Systems From molecules to Human
Description1. Basics Concepts in NMR Spectroscopy2. Analysis of one-dimensional (1D) NMR spectra of molecules3. Introduction to Biological NMR4. Basics of multidimensional 2D and 3D NMR Spectroscopy (NMR methods such as NOESY, TOCSY, Triple rsonance NMR experiments etc.)5. Analysis of 2D/3D NMR spectra of molecules6. Methods to determine 3D Structures of Proteins and Nucleic acids by NMR spectroscopy6. Special Applications: (a) Drug discovery, SAR by NMR, STD, Tr-NOEs (b) Gradients, Imaging and Diffusion (c) Biomolecular Interactions and Supramolecular assemblies. (d) MRS studies of metabolism in Animals and Human
Text Reference
  • Biophysical Chemistry, Vol. 1 & 3. C.R.Cantor and P.R.Schimmel; W.H. Freeman, 1980.
  • Structure and Molecular properties. T.Creighton. W.H.Freeman, 2nd ed. 1992.
  • Protein structure. A practical approach. T.Creighton. Oxford Univ. Press. 2nd ed. 1997.
  • The structure of biological membranes. P.L.Yeagle. CRC Press. 2nd ed. 2004.
Description

Molecular structure; Torsion angles; Steric effect: Contact distances; Homomorphous sugars; cis & trans peptide bonds; Ramachandran map: for amino acids and as a general conformational analysis tool. Non-covalent interactions; hydrogen bond; stacking; Entropy: Entropy/enthalpy compensation; A=T vs. G≡C. Effective conc. Enthalpic and entropic co-operativity. Oligopeptide conformation. Conformationally constrained amino acids; Hydrophobic effect; Affinity and specificity in intermolecular interactions; Stability of protein structure; Folding / unfolding; m values; Models of protein folding; Folding funnel; Contact order; F value analysis; Denatured state; Intrinsically unfolded proteins; Protein and RNA folding; In vivo folding; Kinetically stable proteins; Lipids: Assemblies; Volume, surface area, length relationship; X-ray studies; Phase transitions of anhydrous and hydrated lipid bilayers.

Text ReferenceTitle, Authors, Edition, Publisher, Year 1. R.S. Ochs, R.W. Hanson and J. Halls; Metabolic Regulation. Elsevier, 1985. 2. P.W. Atkins; Physical Chemistry. ELBS, 1981. 3. J.G. Morris; A Biologist`s Physical Chemistry. 1974. 4. Lehninger Principles of Biochemistry. D.L.Nelson and M.M.Cox. 4th ed. W.H.Freeman, 2004. 5. Cellular physiology of nerves and muscles. G.G.Mathews. 4th ed. Blackwell Publishers, 2003. 6. Bioenergetics. D.G.Nicholls and S.J.Ferguson, 2nd ed. Academic Press, 2002.
DescriptionOverview of metabolism; concept of flow of matter and energy; thermodynamics of coupled systems and non-equilibrium reactions; biological energy currencies: high energy bond, reducing power and inter conversions of energy forms; carbon, nitrogen cycles in biosphere; classification of living system based on carbon and energy requirements; methods to study metabolism; carbohydrate and lipid catabolism; glycolysis; TCA cycle; fatty acid oxidation, other metabolic routes of carbon; oxidative phosphorylation; biosynthesis of carbohydrates and lipids photosynthesis; photosynthetic electron transport; Calvin cycle and other avenues of harvesting light energy; gluconeogenesis; Cori cycle; glycogen metabolism; biogenesis of fatty acids and sterols; nitrogen metabolism: sources of organic nitrogen; flow of nitrogen into biosynthesis and catabolism of amino acids; central role of glutamine; purines and pyrimidines; the metabolism of nucleotides; urea cycle and excretion of nitrogen; integration of metabolism and concepts of metabolic regulation.