M.Tech. 4th Sem Industrial BioTechnology Syllabus

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METABOLIC ENGINEERING
Subject Code : 14IBT422

IA Marks : 50
No. of Lecture Hrs./ Week : 04 Exam Hrs : 03
Total No. of Lecture Hrs. : 50 Exam Marks : 100

Course Objectives: To understand fundamental concepts of metabolic pathways and manipulation strategies. To learn and describe material balancing through stoichiometry and analysis. To describe linear programming methods to metabolic flux analysis. To explain experimental methods to determine flux. To learn fundamentals of metabolic flux control and evaluate parametric coefficients. To describe methods to build metabolic networks.

Course Outcomes: At the end of this course, student will be able to:
· Demonstrate fundamental concepts of metabolic pathways and manipulation strategies.
· Apply material balancing methods to evaluate metabolic flux.
· Describe linear programming methods and apply it to metabolic flux analysis.
· Explain experimental methods to determine flux.
· Demonstrate fundamentals of metabolic flux control and Evaluate parametric coefficients.
· Describe methods to build metabolic networks.

MODULE 1 INTRODUCTION TO EXAMPLES OF PATHWAY MANIPULATION – QUALITATIVE TREATMENT 10 Hours
Enhancement of Product Yield and Productivity, Extension of substrate Range, Extension of Product spectrum and Novel products, Improvement of Cellular properties, Xenobiotic degradation.

MODULE 2 MATERIAL BALANCES AND DATA CONSISTENCY 10 Hours
Comprehensive models of cellular reactions; stoichiometry of cellular reactions, reaction rates, dynamic mass balances, yield coefficients and linear rate equations, analysis of over determined systems- identification of gross measurement errors. Introduction to MATLAB®

MODULE 3 METABOLIC FLUX ANALYSIS 10 Hours
Theory, overdetermined systems, underdetermined systems- linear programming, sensitivity analysis, methods for the experimental determination of metabolic fluxes by isotope labeling, applications of metabolic flux analysis.

MODULE 4 METABOLIC CONTROL ANALYSIS 10 Hours
Fundamentals of Metabolic Control Analysis, control coefficients and the summation theorems, Determination of flux control coefficients, MCA of linear pathways, branched
pathways, theory of large deviations

MODULE 5 ANALYSIS OF METABOLIC NETWORKS 10 Hours
Control of flux distribution at a single branch point, Grouping of reactions, case studies, extension of control analysis to intermetabolite, optimization of flux amplifications,
consistency tests and experimental validation.

TEXT / REFERENCE BOOKS
1. Stephanopoulos, G.N. “Metabolic Engineering: Principles and Methodologies”. Academic Press / Elsevier, 1998.
2. Lee, S.Y. and Papoutsakis, E.T. “Metabolic Engineering”. Marcel Dekker, 1998.
3. Nielsen, J. and Villadsen, J. “Bioreaction Engineering Principles”. Springer, 2007.
4. Voit, E.O. “Computational Analysis of Biochemical Systems : A Practical Guide for Biochemists and Molecular Biologists”. Cambridge University Press, 2000.
5. Scheper, T. “Metabolic Engineering” Vol 73 (Advances in Biochemical Engineering Biotechnology) Springer, 2001.
6. Rhodes, P.M. and P.F. Stanbury “Applied Microbial Physiology: Practical Approach”. IRL Press, 1997.
7. Caldwell, D.R. “Microbial Physiology & Metabolism”. Wm. C. Brown, 1995.
8. Rehm, H.J. and G. Reed, “Biotechnology : Products of Primary Metabolism” Vol.6 and “Biotechnology : Products of Secondary Metabolism” Vol.7, VCH / Wiley, 1997.

ADVANCED BIOINFORMATICS
Subject Code : 14IBT421

IA Marks : 50
No. of Lecture Hrs./ Week : 04 Exam Hrs : 03
Total No. of Lecture Hrs. : 50 Exam Marks : 100

Course Objectives: To learn fundamentals of bioinformatics tools. To describe tools for sequence alignment and apply for phylogenetic analysis. To describe tools for pattern
analysis and apply for analysis of motifs and profiles. To describe tools for prediction of protein folding and their applications. To describe tools for tertiary structure prediction and methods of validation. To apply tools of bioinformatics for molecular cloning, primer design, drug design, proteomics, transcriptomics & metabolomics.

Course Outcomes: At the end of this course, student will be able to:
· Describe tools for sequence alignment and apply for phylogenetic analysis.
· Describe tools for pattern analysis and apply for analysis of motifs and profiles.
· Describe tools for prediction of protein folding and their application.
· Demonstrate tools used for tertiary structure prediction and their validation methods.
· Apply tools of bioinformatics for molecular cloning, primer design, drug design, proteomics, transcriptomics & metabolomics.

MODULE 1 10 Hours
SEQUENCE-ALIGNMENT: Sequence databases Formats, querying and retrieval, Nucleic acid & Protein sequence databases, Genome Databases, NCBI, EBI, TIGR, SANGER ; Various file formats for bio-molecular sequences: Similarity matrices; Pair-wise alignment; BLAST; Statistical significance of alignment; Sequence assembly; multiple sequence
alignment; Clustal; Phylogenetics: distance based approaches, maximum parsimony.
PATTERN ANALYSIS IN SEQUENCES: Basic concept and definition of sequence patterns, motifs and profiles, various types of pattern representations viz. consensus, regular expression (Prosite-type) and sequence profiles; trees Motif representation: consensus, regular expressions; PSSMs; Markov models; Regulatory sequence identification using Meme; Gene finding: composition based finding, sequence motif-based finding. Profile-based database searches using PSI-BLAST, analysis and interpretation of profile-based searches.

MODULE 2 FOLD PREDICTION MEHODS 10 Hours
PDB, NDB, Chemical Structure database. Pubchem, Gene Expression database: GEO, SAGE, InterPro, Prosite, Pfam, ProDom, Gene Ontology Structure classification database: CATH, SCOP, FSSP, Protein-Protein interaction databases. Representation of molecular structures (DNA, mRNA, protein), secondary structures, domains and motifs; Protein structure classification, evolution; structural quality assessment; structure comparison and alignment; Visualization software (Pymol, Rasmol etc.); Experimental determination of structures (X-ray crystallography, NMR); Secondary structure prediction; prediction of membrane helices, solvent accessibility; homology modelling, fold recognition methods; RNA structure prediction; Mfold.

MODULE 3 STRUCTURE PREDICTION AND VALIDATION 10 Hours
Tertiary Structure prediction: Fundamentals of the methods for 3D structure prediction (sequence similarity/identity of target proteins of known structure, fundamental principles of protein folding etc.) Homology/comparative modeling, fold recognition, threading approaches, and ab initio structure prediction methods. Force fields backbone conformer generation by Monte Carlo approaches, side-chain packing; Energy minimization; a brief introduction to molecular dynamics Macro-molecular force fields, solvation, long-range forces Geometry optimization algorithms: Steepest descent, conjugate gradient, Various simulation techniques, Molecular mechanics, conformational searches, Molecular Dynamics.
Structure analysis and validation: Pdbsum, Whatcheck, Procheck, Verify3D and ProsaII; Rosetta; Critical assessment of Structure prediction (CASP) Structures of oligomeric proteins and study of interaction interfaces.

MODULE 4: 10 Hours
APPLICATIONS: Role of Bioinformatics in Molecular Cloning, Primer Design, Drug design, Proteomics, Transcriptomics & Metabolomics.
Cloning & Primer Design: Restriction mapping, Web based tools (MAP, REBASE); Primer design – need for tools, Primer design programs and software
Structure-based drug design: Identification and Analysis of Binding sites and virtual screening
Ligand based drug design: Structure Activity Relationship QSARs and QSPRs, QSAR Methodology, In silico prediction ADMET properties for Drug Molecules. Computer-aided
drug design (pharmacophore identification); Protein-Protein interactions. Principles of docking and ligand design. Protein-ligand docking; Vaccine Design Techniques.

MODULE 5: 10 Hours
APPLICATIONS: Chemoinformatics.
Comparative Genomics, Genomes of Viral, Archeal, Bacterial, Eukaryotic genomes with special reference to model organisms (Yeast, Drosophila, C. elegans, Rat, Mouse, Human, plants such as Arabidopsis thaliana, Rice, etc.)
System-wide analyses: Transcriptomics: Microarray technology, expression profiles, data analysis; SAGE; MPSS, Clustering, Probabilistic Models of Evolution, Proteomics: 2D gel electrophoresis; Mass Spectrometry; Protein arrays;
Metabolomics: Metabolic networks in motion: 13C-based flux analysis; Gene Mapping, SNP analysis, Machine learning, Molecular Network Analysis, Probabilistic framework for
modelling and inference, Systems Biology

TEXT / REFERENCE BOOKS:
1. David W. Mount. “Sequence and Genome Analysis”, Bioinformatics CSHL Press, 2nd Ed., 2004.
2. Baxevanis and F. B. F. Ouellette. “Bioinformatics: a practical, guide to the analysis of genes and proteins”, JohnWiley, 2nd Ed., 2001.
3. Jonathan Pevsner. “Bioinformatics and Functional Genomics”, Wiley-Liss, 1st Ed., 2003.
4. Philip E. Bourne & Helge Weissig Tsai. “Structural Bioinformatics”, Wiley, 2003.
5. C. Branden and J. Tooze. “Introduction to Protein Structure”, Garland Publishing, 2nd Ed., 1999.
6. Durbin et al. “Biological Sequence Analysis: Probabilistic models of protein and Nucleic acids”, Cambridge University Press, 2007.
7. Johann Gasteiger and Thomas Engel “Chemoinformatics” Wiley-VCH, 2003.
8. Sheen, David. “Physical Biochemistry”, Wiley & Sons, 2000.
9. Ramakrishnan and Gehrke. “Database Management System”. MGH, 3rd Ed., 2002.

ENTREPRENEURSHIP
Subject Code : 14IBT423

IA Marks : 50
No. of Lecture Hrs./ Week : 04 Exam Hrs : 03
Total No. of Lecture Hrs. : 50 Exam Marks : 100

Course Objectives: To demonstrate the knowledge and understanding of the engineering and management principles in bioprocess industry. To explain types of entrepreneurship, and motivating factors. To identify business opportunities and financing agencies. To understand need and essentials of report writing for financial assistance. To learn and understand role of management and its functions in a business. To learn record maintenance methods and preparation of balance sheets. To know the strategies of marketing and its impact on business.

Course Outcomes: At the end of this course, student will be able to:
· Demonstrate the knowledge and understanding of the engineering and management principles in bioprocess industry.
· Explain types of entrepreneurship, and motivating factors.
· Identify business opportunities and financing agencies.
· Demonstrate the need and essentials of report writing for financial assistance.
· Understand role of management and its functions in a business.
· Apply techniques of record maintenance methods and preparation of balance sheets.
· Understand the strategies of marketing and its impact on business.

MODULE 1 ENTREPRENEURSHIP-ENTERPRISE 10 Hours
Conceptual issues. Entrepreneurship vs. Management. Roles and functions of Entrepreneur in relation to the enterprise and in relation to the economy. Entrepreneurship is an interactive process between the individual and the environment. Small business as seedbed of Entrepreneurship. Entrepreneur competencies, Entrepreneur motivation, performance and rewards.

MODULE 2 OPPORTUNITY SCOUTING AND IDEA GENERATION 10 Hours
Role of creativity and innovation and business research. Sources of business ideas. Entrepreneur opportunities in contemporary business environment, for example opportunities in net-work marketing, franchising, business process outsourcing in the early 21 century. The process of setting up a small business: Preliminary screening and aspects of the detailed study of the feasibility of the business idea and financing/non-financing support agencies to familiarize themselves with the policies/programs and procedures and the available schemes.Preparation of Project Report and Report on Experiential Learning of successful and unsuccessful entrepreneurs.

MODULE 3 MANAGEMENT ROLES AND FUNCTIONS IN A SMALL BUSINESS 10 Hours
Designing and re-designing business process, location, layout, operations planning and control. Basic awareness on the issues impinging on quality, productivity and environment.
Managing business growth. The pros and cons of alternative growth options: internal expansion, acquisitions and mergers, integration and diversification. Crisis in business
growth.

MODULE 4 PRINCIPLES OF DOUBLE-ENTRY BOOK-KEEPING 10 Hours
Journal entries, cash-book, pass book, and Bank Reconciliation Statement, ledger accounts, trail balance and preparation of final accounts: Trading and Profit and Loss Account; Balance-sheet. Brief introduction to Single-Entry system of record keeping. Sources of risk/venture capital, fixed capital, working capital and a basic awareness of financial services such as leasing and factoring.

MODULE 5 ISSUES IN SMALL BUSINESS MARKETING. 10 Hours
The concept and application of product life cycle, advertising and publicity, sales and distribution management. The idea of consortium marketing, competitive bidding/tender
marketing, negotiating with principal customers. The contemporary perspectives on Infrastructure Development, Product and Procurement Reservation, Marketing Assistance, Subsidies and other Fiscal and Monetary Incentives. National state level and grass-root level financial and non-financial institutions in support of small business development.

TEXT / REFERENCE BOOKS
1. Brandt, Steven C., “The 10 Commandments for Building a Growth Company”, Macmillan Business Books, Delhi, 3rd Ed., 1977.
2. Bhide, Amar V., “The Origin and Evolution of New Business”, Oxford University Press, New York, 2000.
3. Dollinger M.J., “Entrepreneurship strategies and Resources”, Pearson Education, New Delhi, 3rd Ed., 2006.
4. Desai, Vasant Dr., “Management of small scale enterprises”, Himalaya Publishing House, 2004.
5. Taneja, Gupta, “Entrepreneur Development New Venture Creation”, Galgotia Publishing Company, 2nd Ed., 2001.
6. Shiba Charan Panda, “Entrepreneurship Development”, New Delhi, Anmol Publications, 1996.
7. Patel, V.G., “The Seven Business Crises and How to Beat Them”, TMH, 1995.
8. SIDBI Report on Small Scale Industries Sector [latest edition]
9. Verma, J.C.., and Gurpal Singh, “Small Business and Industry-A Handbook for Entrepreneurs”, Sage, New Delhi, 2002.
10. Manohar, “Entrepreneurship & Management”, Wiley India, 2012.
11. Schaper, “Entrepreneurship & Small Business”, Wiley India, 2012.
12. Trehan, “Entrepreneurship”, Wiley India, 2012.

RESEARCH METHODOLOGY, BIOSAFETY & IPR
Subject Code : 14IBT41

IA Marks : 50
No. of Lecture Hrs./ Week : 04 Exam Hrs : 03
Total No. of Lecture Hrs. : 50 Exam Marks : 100

Course Objectives: To learn fundamental concepts of doing research and to understand processes involved in performing a research work, and to write a research article or paper using ones own words. To describe and apply statistical techniques to research output and analyze them. To evaluate the research output and present them in the form of report and to be ethically true. To learn the application of softwares in the interpretation of results and data presentation. To understand the importance of intellectual property and methods to safeguard.

Course Outcomes: At the end of this course, student will be able to:
· Explain processes involved in doing research work.
· Identify research problem, formulate and design solution methodologies.
· Apply statistical methods to evaluate and interpret research output.
· Apply knowledge of softwares for data interpretation and data presentation.
· Demonstrate the importance of intellectual properties and research ethics.
· Describe process of Patent application.
· Write a research article or paper without plagiarism.

MODULE 1: 10 Hours
Concept of Research: Types & classification, steps involved. Identification of the research question, hypotheses, and justification for the topic.
Literature Collection: Review of literature, review process and bibliography. Research Objectives and hypothesis.
Research Design: Detailed discussion of the conceptualization and operationalization of variables. Research method and materials, Research action. Data collection and analysis plan: data gathering – thorough description of methods of data gathering and sources.
Scientific writing: Organization and writing of a research papers, short communications, review articles, technical and survey reports, dissertations and books. Organization of
reference material, bibliography, Endnote to be discussed with case studies. Research budget and resources.

MODULE 2: 10 Hours
Introduction to Intellectual Property Rights: Types of IPR: Patents, Trademarks, Copyright & Related Rights, Issues related to plagiarism in research, copyright laws, acknowledging the sources etc to be discussed with case studies. Basics of Patents and Concept of Prior Art; Introduction to Patents; Types of patent applications: Ordinary, PCT, Conventional, Divisional and Patent of Addition; Specifications: Provisional and complete; Forms and fees Invention in context of “prior art”; Patent databases; Searching International Databases; Country-wise patent searches (USPTO, EPO, PATENTScope, WIPO, IPO, etc.).

MODULE 3: 10 Hours
IPR in Research: Traditional Knowledge, Geographical Indications, Protection of GMOs, IP as a factor in R&D; IPs of relevance to Biotechnology and few Case Studies. Patent filing procedures; National & PCT filing procedure; Time frame and cost; Status of the patent applications filed; Precautions while patenting – disclosure/non-disclosure; Financial assistance for patenting – introduction to existing schemes Patent licensing and agreement Patent infringement- meaning, scope, litigation, case studies.

MODULE 4: 10 Hours
Biosafety: Introduction & historical background; Primary Containment for Biohazards; Biosafety Levels for Microbes, Plants & Animals; Biosafety guidelines – Government of
India; Definition of GMOs & LMOs: RCGM, GEAC etc. for GMO applications in food and agriculture; Environmental release of GMOs; Risk Analysis; Risk Assessment; Risk
management and communication. Roles of Institutional Biosafety Committees.

MODULE 5: 10 Hours
Patent laws: History, broad account & latest amendments (if any) of the provisions of Indian Patent Act 1970 & recent amendments, GATT & TRIPS Agreement, Madrid Agreement, Hague Agreement, WIPO Treaties, Budapest Treaty, PCT.

TEXT/REFERENCE BOOKS:
1. C R Kothari, “Research Methodology”, New Age International (P) Ltd. 2008.
2. Kumar. “Research Methodology”, Pearson Education India, 2005.
3. Wayne Goddard, Stuart Melville. “Research Methodology: An Introduction”, Juta and Company Ltd, 2004.
4. Y.K.Singh. “Research methodology: techniques and trends”, APH Publishing, 2007.
5. Kashi Ram Sharma. “Research Methodology”, National publishing house, 2002.
6. D.K. Bhattacharya. “Research Methodology”, Excel Publisher Publishing Co. Pvt. Ltd., 2007.
7. BARE ACT. “Indian Patent Act 1970 Acts & Rules”, Universal Law.
8. Kankanala C. “Genetic Patent Law & Strategy”, 1st Edition, Manupatra Information Solution Pvt. Ltd., 2007.
9. P. Hambleton, J. Melling, T. T. Salusbury. “Biosafety in Industrial Biotechnology”, Springer, 1994.
10. “Laboratory biosafety manual”, World Health Organization, 3rd Ed., 2004.
11. Rajmohan Joshi. “Biosafety and Bioethics”, Isha Books publisher, 2006.
12. M. K. Sateesh. “Bioethics and Biosafety”, IK International, 2008.

Important Links for Resource Material:
1. http://www.w3.org/IPR/
2. http://www.wipo.int/portal/index.html.en
3. http://www.ipr.co.uk/IP_conventions/patent_cooperation_treaty.html
4. www.patentoffice.nic.in
5. www.iprlawindia.org/
6. http://www.cbd.int/biosafety/background.html
7. http://www.cdc.gov/OD/ohs/symp5/jyrtext.htm
8. http://web.princeton.edu/sites/ehs/biosafety/biosafetypage/section

PETROLEUM BIOTECHNOLOGY
Subject Code : 14IBT424

IA Marks : 50
No. of Lecture Hrs./ Week : 04 Exam Hrs : 03
Total No. of Lecture Hrs. : 50 Exam Marks : 100

Course Objectives: To understand concepts of bio-refineries and use of biomolecules in biorefineries.
To describe the processing of methane and aromatic compounds using biocatalysts. To learn concept of bio-corrosion and describe bio-corrosion of various metals and their prevention. To understand emulsification and describe methods of emulsification by biological components. To apply principle of bio-emulsification in sewage treatment. To learn methods of bioremediation and apply them to remediation of oil spills and in petroleum industry waste water treatment.

Course Outcomes:
At the end of this course, student will be able to:
· Understand concept of bio-refineries and their applications.
· Describe processing of methane and aromatic compounds using biocatalysts.
· Demonstrate biological corrosion and methods to combat them.
· Describe emulsification methods used for industrial application using biological materials.
· Apply bio-emulsification method to sewage water treatment process.
· Describe bioremediation process and apply it to petroleum industry waste water treatment.

MODULE 1 BIOREFINARIES 10 Hours
Petroleum biotechnology as an integrated approach, microbial diversity in oil reservoirs and DNA fingerprinting, Potential use of biocatalyst in oil refineries, extremophiles and oil refineries – a new application. Bio-desulfurization – enzymatic treatments; Biodenitrogenation of petroleum; Enzymatic transformation of asphaltenes.

MODULE 2 BIOPROCESSING OF METHANE AND AROMATIC COMPOUNDS 10 Hours
Bioprocessing of crude oils and distillates in oil-water system, aromatic bioprocessing biocatalysts and its genetic engineering. Aromatic bioprocessing of BioARC (Biological
Aromatic Ring Cleavage). Biological distribution and classification of methane monooxygenases, soluble methane monooxygenase, Methane monooxygenase in biocatalysts and Biomimetics.

MODULE 3 BIOCORROSION 10 Hours
Bio-corrosion of steel, aluminum alloy in fuel/water system; aerobic corrosion of iron; microbial inhibition of corrosion, electrochemical interpretation of bio-corrosion; prevention, control and monitoring of bio-corrosion; Molecular tools in bio-corrosion – DNA hybridization technique.

MODULE 4 BIOEMULSIFIERS 10 Hours
Low molecular weight bio-surfactants; Bio-emulsifiers – Protein Polysaccharide interactions, emulsan paradigm, microbial sources, engineering of novel emulsans; Polymeric bioemulsifiers – Alasan, Liposan, Biodispersan, Production techniques of bio-emulsifiers.
Application – Bio-emulsification, cleaning and sludge recovery, viscosity reduction and oil transportation.

MODULE 5 BIOREMEDIATION 10 Hours
Phytoremediation: mechanisms and pilot studies, and mathematical modeling.
Bioremediation of Marine Oil spills: Anthropogenic input of oil into ocean, Physical fate of spilled oil, eventual fate of spilled oil, spill response – at sea, on shore.
Biotreatment of water pollutants from the Petroleum industry: Anaerobic biodegradation and biotransformation, Biotransformation of S- and N- bearing inorganic compounds, Oxygenated fuel additives (MTBE biodegradation).

TEXT / REFERENCE BOOKS:
1. Duhalt and Ramirez (Ed.), “Petroleum Biotechnology: Developments and Perspectives”, Elsevier 2004.
2. Videla, Wilkes and Silva, “Manual of Biocorrosion”, CRC Press, 1st Ed., 1997.
3. Stevens, Sequiera and Tiller, “Microbial Corrosion – 1”, Springer, 1988.
4. James Speight and Karuna Arjoon, “Bioremediation of Petroleum and Petroleum products”, Wiley-Scrivener, 1st Ed., 2012.
5. Robert E. Hinchee, Jeffrey A. Kittel, H. James Reisinger, “Applied Bioremediation of Petroleum Hydrocarbons”, Vol 3, Battelle Press, 1995.

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