M.tech Biotechnology Final 2012-13 (New)

GANDHI INSTITUTE OF TECHNOLOGY AND MANAGEMENT

(GITAM) (Deemed to be University, Estd. u/s 3 of UGC Act 1956)

VISAKHAPATNAM HYDERABAD BENGALURU Accredited by NAAC with ‘A’ Grade

REGULATIONS & SYLLABUS

Of

Master of Technology in

Biotechnology

(Drug Design and Development) Programme Code: EPRBT201001

(W.e.f 2012-13 admitted batch)

Website: www.gitam.edu

1

M.Tech. Biotechnology

(Drug Design and Development)

REGULATIONS

Programme Code: EPRBT201001 (w.e.f. 2012-13 admitted batch)

1.0 ADMISSIONS

1. Admissions into M.Tech. (Biotechnology) programme of GITAM University

are governed by GITAM University admission regulations.

2.0 ELIGIBILTY CRITERIA

2.1 A pass in B. E. / B. Tech. or equivalent in Biotechnology or B. Pharm. or

equivalent or B. Tech. in Chemical Engg. / M. Sc. in Chemistry with Basic

Biology/ M.Sc. Biotechnology or M Sc in any Biological Science with

Mathematics.

2.2 Admissions into M.Tech. will be based on the following:

Score obtained in GAT (PG), if conducted.

Performance in Qualifying Examination / Interview.

The actual weightage is to be given to the above items will be decided by the

authorities before the commencement of the academic year. Candidates with

good GATE/GRE score shall be exempted from appearing for GAT (PG).

3.0 STRUCTURE OF THE M.Tech. PROGRAMME

3.1 The Programme of instruction consists of:

(i) A core programme imparting to the student specialization of

engineering branch concerned.

(ii) Separate remedial courses may be prescribed for engineering & science

students.

(iii) Carry out a technical project approved by the Department and submit a

report.

3.2 Each academic year consists of two semesters. Every branch of the M.Tech.

programme has a curriculum and course content (syllabi) for the subjects

recommended by the Board of Studies concerned and approved by

Academic Council.

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3.3 Project Dissertation has to be submitted by each student individually.

4.0 CREDIT BASED SYSTEM

4.1 The course content of individual subjects - theory as well as practicals – is

expressed in terms of a specified number of credits. The number of credits

assigned to a subject depends on the number of contact hours (lectures &

tutorials) per week.

4.2 In general, credits are assigned to the subjects based on the following contact

hours per week per semester.

One credit for each Lecture hour.

One credit for two hours of Practicals.

Two credits for three (or more) hours of Practicals.

4.3 The curriculum of M.Tech programme is designed to have a total of 70 -85

credits for the award of M.Tech degree. A student is deemed to have

successfully completed a particular semester‟s programme of study when he /

she earns all the credits of that semester i.e., he / she has no „F‟ grade in any

subject of that semester.

5.0 MEDIUM OF INSTRUCTION

The medium of instruction (including examinations and project reports) shall be

English.

6.0 REGISTRATION

Every student has to register himself/herself for each semester individually at the

time specified by the College / University.

7.0 CONTINUOUS ASSESSMENT AND EXAMINATIONS

7.1 The assessment of the student‟s performance in each course shall be

based on continuous evaluation and semester-end examination. The

marks for each component of assessment are as shown in the Table 1.

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Table 1: Assessment Procedure

S.

No.

Component of

Assessment

Marks

Allotted

Type of

Assessment Scheme of Examination/Evaluation

1

Theory

40 Continuous

Evaluation

i) Thirty (30) marks for mid Semester examinations. Three

mid examinations shall be conducted for 15 marks

each; performance in best two shall be taken into

consideration.

ii) Ten (10) marks for Quizzes, Assignments and

Presentations.

60 Semester-end

Examination Sixty (60) marks for Semester-end examinations

Total 100

2 Practicals 100 Continuous

Evaluation

i) Fifty (50) marks for regularity and performance, records

and oral presentations in the laboratory. Weightage for

each component shall be announced at the beginning of

the Semester.

ii) Ten (10) marks for case studies.

iii) Forty (40) marks for two tests of 20 marks each

(one at the mid-term and the other towards the end of the

Semester) conducted by the concerned lab Teacher.

3

Project work

(Interim

evaluation – III

semester )

100 Continuous

Evaluation

i) Forty (40) marks for periodic evaluation on originality,

innovation, sincerity and progress of the work, assessed

by the Project Supervisor.

ii) Thirty (30) marks for mid-term evaluation for defending

the Project, before a panel of examiners*.

iii) Thirty (30) marks for final Report presentation and Viva-

voce, by a panel of examiners*

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Project work

(Final evaluation

– IV semester )

50 Continuous

Evaluation

i) Twenty (20) for periodic evaluation on originality,

innovation, sincerity and progress of the work, assessed

by the Project Supervisor.

ii) Fifteen (15) marks for mid-term evaluation for defending

the Project, before a panel of examiners*.

iii) Fifteen (15) marks for interim Report presentation and

Viva-voce.

50 Semester-end

Examination

Fifty (50) marks for final Report presentation and

Viva-voce assessed by external examiners.

5

Comprehensive

Viva

100

Continuous

Evaluation

Through five periodic Viva-voce exams for

20 marks each, conducted by a panel of examiners*.

The course content for Viva exams shall be announced at

the beginning of the Semester.

*Panel of Examiners shall be appointed by the concerned Head of the Department.

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8.0 REAPPEARANCE

8.1 A Student who has secured „F‟ Grade in any theory course / Practicals of any

semester shall have to reappear for the semester end examination of that

course / Practicals along with his / her juniors.

8.2 A student who has secured „F‟ Grade in Project work shall have to improve

his report and reappear for viva – voce Examination of project work at the

time of special examination to be conducted in the summer vacation after the

last academic year.

9.0 SPECIAL EXAMINATION

9.1 A student who has completed the stipulated period of study for the degree

programme concerned and still having failure grade („F‟) in not more than

5 courses ( Theory / Practicals), may be permitted to appear for the special

examination, which shall be conducted in the summer vacation at the end

of the last academic year.

9.2 A student having „F‟ Grade in more than 5 courses (Theory/practicals)

shall not be permitted to appear for the special examination.

10.0 ATTENDANCE REQUIREMENTS

10.1 A student whose attendance is less than 75% in all the courses put together

in any semester will not be permitted to attend the end - semester

examination and he/she will not be allowed to register for subsequent

semester of study. He /She has to repeat the semester along with his / her

juniors.

10.2 However, the Vice Chancellor on the recommendation of the Principal /

Director of the University college / Institute may condone the shortage of

attendance to the students whose attendance is between 66% and 74% on

genuine medical grounds and on payment of prescribed fee.

11.0 GRADING SYSTEM

11.1 Based on the student performance during a given semester, a final letter

grade will be awarded at the end of the semester in each course. The letter

grades and the corresponding grade points are as given in Table 2.

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Table 2: Grades & Grade Points

11.2 A student who earns a minimum of 5 grade points (C grade) in a course is

declared to have successfully completed the course, and is deemed to have

earned the credits assigned to that course. However, a minimum of 24

marks is to be secured at the semester end examination of theory courses in

order to pass in the theory course.

11.3 Marks for project work and for electives taught by different teachers, will

be examined, and scaling may be applied if necessary.

11.4 No credits will be awarded for remedial courses and free-electives. If the

student manages to secure more than 50% marks for any of the free-

electives, an S grade (satisfactory) will be awarded, otherwise a U grade

(unsatisfactory) will be awarded.

12.0 GRADE POINT AVERAGE

12.1 A Grade Point Average (GPA) for the semester will be calculated

according to the formula:

Σ [ C x G ]

GPA = ----------------

Σ C

Where

C = number of credits for the course,

G = grade points obtained by the student in the course.

12.2 Semester Grade Point Average (SGPA) is awarded to those candidates who

pass in all the subjects of the semester.

12.3 To arrive at Cumulative Grade Point Average (CGPA), a similar formula is

used considering the student‟s performance in all the courses taken in all

the semesters completed up to the particular point of time.

12.4 The requirement of CGPA for a student to be declared to have passed

on successful completion of the M.Tech. programme and for the

declaration of the class is as shown in Table 3.

Grade Grade points Absolute Marks

O 10 90 and above

A+ 9 80 – 89

A 8 70 – 79

B+ 7 60 – 69

B 6 50 – 59

C 5 40 – 49

F Failed, 0 Less than 40

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Table 3: CGPA required for award of Degree

Distinction ≥ 8.0*

First Class ≥ 7.0

Second Class ≥ 6.0

Pass ≥ 5.0

* In addition to the required CGPA of 8.0, the student must have necessarily passed

all the courses of every semester in first attempt.

13.0 ELIGIBILITY FOR AWARD OF THE M.Tech. DEGREE

13.1 Duration of the programme:

A student is ordinarily expected to complete the M Tech. programme in

four semesters of two years. However a student may complete the

programme in not more than four years including study period.

13.2 However the above regulation may be relaxed by the Vice Chancellor in

individual cases for cogent and sufficient reasons.

13.3 Project dissertation shall be submitted on or before the last day of the

course. However, it can be extended up to a period of 6 months maximum,

with the written permission of the Head of the Department concerned.

13.4 A student shall be eligible for award of the M.Tech. degree if he / she

fulfils all the following conditions.

a) Registered and successfully completed all the courses and projects.

b) Successfully acquired the minimum required credits as specified in the

curriculum corresponding to the branch of his/her study within the

stipulated time.

c) Has no dues to the Institute, hostels, Libraries, NCC / NSS etc, and

d) No disciplinary action is pending against him / her.

e) Following is applicable to students admitted to M.Tech. (Biotechnology)

course without a B.Tech. (Biotechnology) degree:

Successfully completed additional remedial courses at B.Tech. Level

prescribed by BOS.

Additional remedial courses may be prescribed by the Board of Studies for

students who do not have a B.Tech. (Biotechnology) degree based on

examination of their syllabus.

13.5 The degree shall be awarded after approval by the Academic Council.

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RULES

1. With regard to the conduct of the end-semester examination in any of the practical

courses of the programme, the Head of the Department concerned shall appoint

one examiner from the department not connected with the conduct of regular

laboratory work, in addition to the teacher who handled the laboratory work

during the semester.

2. In respect of all theory examinations, the paper setting shall be done by an

external paper setter having a minimum of three years of teaching experience. The

panel of paper setters for each course is to be prepared by the Board of Studies of

the department concerned and approved by the Academic Council. The paper

setters are to be appointed by the Vice Chancellor on the basis of recommendation

of Director of Evaluation / Controller of Examinations.

3. The theory papers of end-semester examination will be evaluated by two

examiners. The examiners may be internal or external. The average of the two

evaluations shall be considered for the award of grade in that course.

4. If the difference of marks awarded by the two examiners of theory course

exceeds 12 marks, the paper will have to be referred to third examiner for

evaluation. The average of the two nearest evaluations of the three shall be

considered for the award of the grade in that course.

5. Panel of examiners of evaluation for each course is to be prepared by the Board

of Studies of the department concerned and approved by the Academic Council.

6. The examiner for evaluation should possess post graduate qualification and a

minimum of three years teaching experience.

7. The appointment of examiners for evaluation of theory papers will be done by the

Vice Chancellor on the basis of recommendation of Director of Evaluation /

Controller of Examinations from a panel of examiners approved by the Academic

Council.

8. Project work shall be evaluated by two examiners at the semester end

examination. One examiner shall be internal and the other be external. The Vice

Chancellor can permit appointment of second examiner to be internal when an

external examiner is not available.

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M.Tech. (Biotechnology) - Scheme of Instruction

Course Code Name of the Course Instruction hours Maximum marks Credit

s

L T P Total Cont Sem Total

Semester 1

EPRBT 101 Regulatory issues in drug design and

development

3 - - 3 40 60 100 3

EPRBT 102 Physiology and Pharmacology 3 - - 3 40 60 100 3

EPRBT 103 Advanced genetics and genetic engineering 3 - - 3 40 60 100 3

EPRBT 104 Fermentation and cell culture 3 - - 3 40 60 100 3

EPRBT 121

EPRBT 122

EPRBT 123

EPRBT 124

EPRBT 125

Remedial courses:

Molecular biology and genetic engineering*

Introduction to biochemical engineering*

Applicable mathematics*

Research Methodology *

Protein Chemistry*

3

6

6

3

3

-

-

-

-

-

-

-

-

-

-

3

6

6

3

3

40 60 100 -

EPRBT 126

EPRBT 127

Free Elective

Nanobiotechnology

Bioelectronics

3 - - 3 100 -- 100 -

EPRBT 111 Pharmacology and genetic engineering lab - - 6 6 100 -- 100 2

EPRBT 112 Fermentation and cell culture lab - - 6 6 100 -- 100 2

EPRBT 113 Seminar - 3 - 3 100 -- 100 3

Total 30 19

Semester 2

EPRBT 201 Pharmacoinformatics 3 - - 3 40 60 100 3

EPRBT 202 Proteomics and genomics for target

identification

3 - - 3 40 60 100 3

EPRBT 203 Screening and target validation 3 - - 3 40 60 100 3

EPRBT 204 Biological programming 3 - - 3 40 60 100 3

EPRBT 221

EPRBT 222

EPRBT 223

Elective

Advanced Instrumental methods of analysis

Molecular Diagnostics

Tissue engineering

3 - - 3 40 60 100 3

EPRBT 211 Pharmacoinformatics lab - - 6 6 100 -- 100 2

EPRBT 212 Biological Programming Lab - - 6 6 100 -- 100 2

EPRBT 213 Seminar - 3 - 3 100 -- 100 3

Total 30 22

Semester 3

EPRBT 301 Molecular modeling and lead optimization 3 - - 3 40 60 100 3

EPRBT 302 Modeling and simulation of drug

manufacturing process

3 - - 3 40 60 100 3

EPRBT 311 Molecular modeling lab - - 6 6 100 -- 100 2

EPRBT 312 Modeling and simulation lab - - 6 6 100 -- 100 2

EPRBT 313 Project - - - 15 100 -- 100 10

EPRBT 314 Industrial Training Report 100 -- 100 2

Total 33 22

Semester 4

EPRBT 411 Project - - - 35 50 50 100 20

Total 35 20

Grand Total 83

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M.Tech. Biotechnology – I SEMESTER

REGULATORY ISSUES IN DRUG DESIGN AND DEVELOPMENT

Course Code : EPRBT 101

Credits : 3 Hours: 3 per week

UNIT I

Quality control: GMP. Purity determination as per ICH guidelines.

UNIT II

Intellectual Property: Concepts and Fundamentals :Mechanisms for

protection of Intellectual Property- patents, copyright, trademark; factors

affecting choice of IP protection; penalties for violation, Role of IP in

Pharma Industry.

Trade related aspects of Intellectual Property Rights: Intellectual Property

and International Trade: Concepts behind WTO (World Trade

Organization),WIPO (World Intellectual Property Organization) GATT

(General Agreement on Tariff and Trade), TRIPs (Trade Related Intellectual

Property Rights), TRIMS (Trade Related Investment Measures) and GATS

(General Agreement on Trade in Services); Protection of plant and animal

genetic resources; biological materials; gene patenting. Case studies and

examples.

UNIT III

Nuts and Bolts of patenting, copyright and trademark protection:

Criteria for patentability, types of patents; Indian Patent Act, 1970. Filing of

a patent application: Precautions before patenting- disclosure/non-disclosure,

publication-article/thesis; Prior art search- published patents, internet search,

patent sites, specialized services- search requests, costs; Patent Application-

Forms and guidelines, fee structure, time frames, jurisdiction aspects. Types

of patent applications- provisional, non-provisional, PCT and convention

patent applications; International Patenting- Requirements, procedures and

costs; Publication of Patents; Patent Annuity; rights and responsibilities of a

patentee. Patent infringement. Case studies: Drug related patents and

infringements.

UNIT-IV Patenting by research students, lecturers and scientists-

University/organizational rules. Thesis, Research Paper Publication, credit

sharing by workers, financial incentives; Useful information sources for

patents related information.

Significance of copyright protection for researchers; Indian Copyright Law

and digital technologies- Berne convention, WIPO copyright treaty (WCT),

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WIPO performance and Phonograms Treaty (WPPT); Protection for

computer databases, multimedia works; Trademarks legislation and

registration system. Meaning of trademark, criteria for eligibility. Trade

secrets-scope, modalities and protection.

UNIT V

Technology Development/Transfer/Commercialization related aspects:

Drug related technology development. Toxicological studies, Bioequivalence

(BU), Clinical Trials-Phase 1,Phase II and Phase III. Approved Bodies and

Agencies. Scale-up, semi-commercialization and commercialization.

Managing technology transfer (TOT). Compulsory Licensing, access to

medicine issues; DOHA declaration, POST WTO Product Patent Regime

from 2005.

Drug Registration and Licensing Issues. Drug Master file submissions,

SOPS; Funding sources for commercialization of Technology: Preparation

of a project report, financial appraisal. Business models. Case Study :

Antiretroviral drugs.

Text books:

1. The Generic Challenge: Understanding Patents, FDA and pharmaceutical

life-cycle management by M.A.Voet

2. Biotechnology and Pharmaceutial Patents: Law and Practice by Marc S.

Gross, S. Peter Ludwig, Robert C., Jr. Sullivan

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PHYSIOLOGY AND PHARMACOLOGY

Code : EPRBT 102 Credits : 3 No. of hours: 3 per week

UNIT-I

Pharmacokinetics: Mechanisms, factors affecting and kinetics of

Absorption, Distribution, Metabolism (hepatic clearance) and elimination

(renal clearance) of drugs. Binding, Potency, efficacy, therapeutic index,

margin of safety, dose optimization. Formulation of therapeutics (small

molecule and biologicals). Toxicity. Concept of Adverse drug reactions and

drug interactions. Drug transporters in drug disposition, interaction and

resistance.

UNIT-II

Computational Approaches in Phamacokinetics :Bioequivalence and

bioavailability studies. Estimation of pharmacokinetic parameters. Wagner-

Nelson calculation of bioavailability and Assessment of bioavailability,

Physiology-Based Pharmacokinetic (PBPK) Modelling.

UNIT-III

Physiology, common diseases, drugs, targets and modes of action of drugs of

the nervous system. Physiology, common diseases, drugs, targets and modes

of action of drugs of the musculoskeletal systems. Physiology, common

diseases, drugs, targets and modes of action of drugs of the endocrine,

gastroenteric and excretory systems.

UNIT-IV

Physiology, common diseases, drugs, targets and modes of action of drugs of

the cardiovascular and respiratory system. Physiology, common diseases,

drugs, targets and modes of action of drugs of the immune system.

UNIT-V

Molecular basis of cancer. Tumor pathology, classification and treatment of

cancers. Targets and modes of action of major anti-cancer drugs. Drugs and

targets for the infectious diseases: Tuberculosis and Malaria.

Textbooks:

1. Textbook of physiology by Guyton

2. Brody's Human pharmacology: Molecular to clinical by K.P.Minneman

(2004)

3. Pharmacology by Satoshkar and Bandarkar

12

Reference books:

1. Clinical Pharmacokinetics: Concepts and Applications, M.Rowland and

T.N. Tozer, 3rd edition, Lea and Febiger, Philadelphia, 1995.

2. Pharmacokinetics and Pharmacodynamics of Biotech Drugs: Principles and

Case Studies in Drug Development - Edited by Bernd Meibohm, WILEY-

VCH Verlag GmbH & Co. KGaA, Weinheim, Germany – 2006.

3. Basic Clinical Pharmacokinetics, Michael Winter, 4th edition, Lippincott,

Williams&Wilkins, Philadelphia, 2004.

4. Applied Biopharmaceutics and Pharmacokinetics, L. Shargel and A.B.C.

Yu, 5th edition, Appleton and Lange, Norwalk, CT, 2005.

5. Drug metabolism in drug design and development. Zhang, Zhu and

Humphreys. (2007) Wiley-Interscience.

6. Introduction to drug metabolism. Gibson and P. Skett. 3rd

Ed. (2001).

Nelson Thornes.

7. Reviews of Medical Physiology by W.F.Ganong

8. Pharmacology by Rang and Dale.

9. Medical microbiology. 24th Edition (Jawetz, Melnick and Adelberg's

Medical Microbiology) by Geo. F. Brooks. (2007)

13


ADVANCED GENETICS AND GENETIC ENGINEERING


UNIT-I

Genetic polymorphism. Genetic variability in drug metabolizing enzymes,

drug transporters and drug receptors. Immunogenetic polymorphisms.

Methods for genotyping.

Case study: Host genetics and tuberculosis susceptibility.

UNIT-II

Monogenic traits: Mendelian pedigree patterns. Linkage analysis, Pedigree

analysis. Hardy-Weinberg Law. Allele frequency estimation for two alleles

and three alleles at a locus. Linkage disequilibrium and Association

mapping.

UNIT-III

Multifactorial inheritance. Heritability. Twin studies in pharmacogenetics.

Interval mapping. Polygenic models. Haplotyping.

UNIT-IV

Genetic engineering for gene therapy: Therapeutic nucleic acids.

Therapeutic genes used in clinical trials. Gene knockout and knockin. RNAi.

Methods for gene delivery. Viral vectors (Gammaretroviruses, lentiviruses,

adenoviruses, adeno-associated viruses, herpes simplex virus).

UNIT-V

Gene therapy: Gene therapy for immune system diseases. Gene therapy of

neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's and

ALS). Gene therapy of eye diseases. Gene therapy of cardiovascular

diseases. Gene therapy for cancer.

Text books:

1. J.W.Larrick and K.W.Burck. Gene therapy: applications of molecular

biology. Elsevier. 1991.

2. J-M. H. Vos. Viruses in gene therapy. Chaptman and Hall. 1995.

3. W.Weber. (2008). Pharmacogenetics. Oxford University Press.

4. Strachan and Read. (2004) Human Molecular Genetics 3, Garland Press.

Reference Books:

1. D.A.P.Evans. (1994) Genetic factors in drug therapy: Clinical and molecular

pharmacogenetics. Cambridge University Press.

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2. I.P.Hall and M.Pirmohamed. (2006). Pharmacogenetics. Informa healthcare.

3. K.Lange. Mathematical and statistical methods for genetic analysis. 2nd

Ed.

(2003) Springer.

4. M. Giacca. Gene therapy. 2010. Springer.

5. KK Hunt, SA Vorburger and SG Swisher. Gene therapy for cancer. Humana

press (2007).

6. Genetics. Hartl and Jones, Jones and Bartlett publishers (2005)

7. Introduction to quantitative genetics, Falconer and Mckay 4th

Edition.

8. Reference for case study 1) Current science. Vol.86 #1 (2004)

15


FERMENTATION AND CELL CULTURE

Course Code: EPRBT 104 Credits : 3 Hours: 3 per week

UNIT-I

Metabolic engineering: Flux control analysis, Flux control coefficients,

summation theorem, elasticity coefficient, connectivity theorem.

Genetic engineering: Genetically engineered microbes for production of

antibiotics. Production of penicillin and semisynthetic analogs of penicillin.

Production of insulin and insulin analogs. Use of humanized yeast for

glycosylation.

UNIT-II

Pharmaceutical production using plant cell culture: Production of Digoxin

from cultured cells of Digitalis lanata. Production of Shikonin from cultured

cells of Lithospermum erythrorhizon.

Biopharming: Agrobacterium mediated genetic engineering for production of

biopharmaceuticals from plants. Engineered viral vectors for

biopharmaceutical production. Hirudin production from Brassica napus.

Edible vaccines from transgenic banana plants.

UNIT-III Animal cell culture and its applications. Equipment and media for animal cell

culture. The insect cell-baculovirus system. Production of haematopoeitic

growth factors (thrombopoeitin and GCSF (lenograstim)), cytokines (IL2, -

interferon), and cytokine inhibitors (TNF inhibitors: infliximab,

adalimumab, etanercept).

UNIT-IV

Types of cell lines. Transformed human cell lines and their applications.

Embryonic stem cells and adult stem cells (hematopoietic stem cells,

neuronal stem cells) and their therapeutic applications. Organ culture of

skin.

UNIT-V

Engineering and regulatory issues in the scale up of fermentation processes:

Scale-up of manufacturing involving hazardous microbes – disinfection and

inactivation procedures. Verification of inactivation process at scale.

Security of stock cultures. NIH guidelines for minimum containment

requirements for different risk level agents. Regulations for biosafety related

to production of bioprocess-based pharmaceuticals.

16

Textbooks:

Glazer and Nikaido. Microbial biotechnology: Fundamentals of Applied

Microbiology. 2nd

Ed. (2007)

S. Ozturk and Wei-shou Hu. Ed. Cell culture technology for pharmaceutical

and cell-based therapies (Biotechnology and Bioprocessing series). (2005)

CRC.

Biological safety: principles and practices. By Diane O. Fleming, Debra Long

Hunt. Chapter 34. Biosafety in the pharmaceutical industry. ASM Press.2000.

(For Unit-V)

References:

1. M.El-Mansi, C.F.Bryce, A.L.Demain and A.R.Allman. Fermentation

microbiology and biotechnology. Taylor and Francis.

2. V.A.Vinci and S.R.Parekh. Ed. Handbook of industrial cell culture:

Mammalian, microbial and plant cells. (2002). Humana Press.

3. Stephanopoulos. Metabolic engineering. (1998) Academic Press. (Unit-I)

4. Andrian Slater. Nigel W.Scott. “Plant biotechnology: The genetic manipulation

of plants‟. (2006) 2nd

Edn. Oxford press.

5. D. Balasubramanian, CFA Bryce, K.Dhamalingam, J.Green and Kunthala

Jayaraman „Concepts in Biotechnology‟ Revise edition Universities press

17


MOLECULAR BIOLOGY AND GENETIC ENGINEERING

Course Code : EPRBT 121 Credits : 0 Hours: 3 per week

UNIT-I

Genome organization in prokaryotes and eukaryotes. Review of Replication.

Epigenetic methods of inheritance. Plasmids. Group I introns. Group II

introns. LINEs and SINEs. Vectors for bacteria, yeast and animal cells.

Case study: Homologous recombination in mycobacteria.

UNIT-II Review of transcription and translation. Regulatory mechanisms.

Posttranscriptional regulatory mechanisms. SnRNPs. Spliceosome structure

and function. Posttranslational regulatory mechanisms. MicroRNAs. RNAi.

Case study: Transcriptional regulation in mycobacteria.

UNIT-III Major signal transduction pathways and regulation of the Cell cycle.

Transport mechanisms. Regulatory mechanisms of metabolic and signal

transduction pathways: feedback and feedforward controls.

Case study: Signal transduction systems of mycobacteria.

UNIT-IV Methods: DNA sequencing by Sanger's method. High throughput DNA

sequencing methods. Protein sequencing by Edman degradation and by Mass

spectrometry. Oligonucleotide synthesis. Solution phase and solid phase

peptide synthesis.

UNIT-V Review of transformation, transduction and conjugation in bacteria.

Restriction and ligation. Construction and screening of libraries. Site-

specific, casette mutagenesis and transposon based mutagenesis. Introduction

to PCR and microarray technology. Construction and screening of a

subtractive cDNA library.

Text books:

1. H.D. Watson, T.Baker, S.P.Bell, A.Gann, M.Levine, R.Losick. Molecular Biology of

the gene.6th

Ed. (2007) Benjamin Cummings.

2. Alberts et al. Molecular biology of the cell. 4th

Ed. (2002) Garland publishers.

3. Molecular cell biology. Lodish et al. 5th

Ed. (2003) W.H.Freeman.

References:

1. Primrose and Twyman. Principles of gene manipulation and genomics. 7th

Ed. (2006)

Blackwell publishers.

2. B.Lewin. Genes-IX. 9th

Ed. (2007). Jones and Bartelett publishers.

3. B.K.Nunnaly. Analytical techniques in DNA sequencing. (2005). CRC Press.

4. Current Science. Vol.86#1. (2004)

18


INTRODUCTION TO BIOCHEMICAL ENGINEERING

Code : EPRBT 122 Credits: 0 No. of hours: 6 per week

UNIT – I

Fluid Mechanics : Properties of Fluids, Types of Fluids, Laminar and

Turbulent Flow, Basic equations of fluid flow: Conservation of mass,

conservation of energy, Boundary Layer, Hagen-Poiseuille equation, Flow

through porous media, Fluidization.

(Chapter-4: Introduction to Chemical Engineering by S.K.Ghosal &

S.K.Sanyal

UNIT-II

Conduction: Fourier‟s Law of Heat Conduction, Conduction through a

composite plane wall. Conduction through resistances in parallel.

Convection: Definitions of Natural convection and forced convection,

individual heat transfer coefficients, correlations for calculation of heat

transfer coefficients, Heat Transfer with phase change, overall heat transfer

coefficient, LMTD. Radiation: Black body Radiation, Radiation from the

sun. Heat Transfer Equipment: Double Pipe Heat Exchanger. Shell and

Tube Heat Exchanger, Extended Surface Heat Exchanger.


S.K.Sanyal)

(Note: Problems may come from conduction through a composite plane wall

only)

UNIT-III

Diffusion: Fick‟s Law, Diffusivity of fluids, Steady State diffusion of fluids.

Inter phase Mass Transfer: Mass Transfer coefficient, relation between mass

transfer coefficients, overall mass transfer coefficient. Absorption: Choice of

solvent for absorption, material balance for counter current absorption

process, HETP. Distillation: Concept of VLE, relative volatility, concept of

simple, flash, steam, fractional distillation, calculation of number of

theoretical stages by Mc-Cabe-Thiele method, plate efficiency. Liquid-

Liquid Extraction: Liquid-Liquid Equilibria, distribution coefficient, choice

of solvent for extraction, material balance for single stage extraction

operation.


S.K.Sanyal)

(Note: Distillation problems may be given on Mc-Cabe- Thiele method

only).

19

UNIT-IV

Chemical Reaction Engineering & Bioreactor Design: Kinetics of

Homogeneous reactions, single and multiple reactions. Elementary & Non

elementary reactions; molecularity and order of reactions; representation of

reactions; testing kinetic models. Temperature-dependent term of a rate

equation (Chapter-2 of O.Levenspiel, 3e). Interpretation of Batch Reactor

Data: Constant Volume Batch Reactor; Integral Method of Analysis;

Differential variable – Volume Batch Reactor (Chapter -3, O.Levenspiel, 3e).

Simple problems based on the three chapters. Single Ideal Reactors:

Performance equations for batch reactors, Fed Batch reactors, MFR and PFR

(Chapter – 5, O.Levenspiel, 3e).Basic Concept of Non-ideal Flow and RTD.

UNIT-V

Material and Energy balances – Stoichiometry. Batch and continuous

sterilization of media – substrate utilization and product formation kinetics-

Microbial kinetics, Bioreactor and its accessories, types of bioreactors in

brief – Oxygen transfer in microbial systems, oxygen demand, KLa

measurement – Power requirement – Monitoring of Bioprocess variables –

Product Recovery – Isolation, Purification, Crystallization and Drying – One

Case Study, Simple problems based on the above.

Scope: As given in the book “Introduction to Chemical Engineering by

S.K.Ghosal & S.K.Sanyal”, Tata Mc Graw Hill Publishing House, New

Delhi.

Text Books:

1. Introduction to Chemical Engineering by S.K.Ghosal & S.K.Sanyal, Tata

Mc Graw Hill Publishing House, New Delhi.

2. Chemical Reaction Engineering by Octave Levenspiel., 3rd

edition. John

Wiley. 1999

20


APPLICABLE MATHEMATICS


UNIT-I

Solving simultaneous linear equations in 2 and 3 variables using matrix

inverse method and Cramer‟s rule. Eigen values and eigenvectors of

matrices. Sums and products of trigonometric functions. Equation of line

and plane in three dimensions.

UNIT –II

Differential and Integral Calculus: Methods of differentiation. Elementary

methods of integration.

Partial differentiation: Partial derivative and total derivative of functions of

more than one variable. Euler's theorem. Cartesian, cylindrical and spherical

coordinate systems and transformation rules.

Vector Calculus: Properties of Gradient, divergence and curl. Line integrals.

Area, surface and volume.

UNIT –III

Representation of a complex number. Modulus and amplitude of a complex

number. Cauchy's integral formula. Residue theorem and contour

integration.

Ordinary Differential equations: Solution of differential equations of first

order and first degree using the method of separation of variables. Brief

description of other methods of solving first order differential equations (no

numericals). Simultaneous linear equations with constant coefficients.

Cauchy's and Legendre's linear equations.

UNIT- IV

Partial differential equations: The Laplacian in cartesian and cylindrical

coordinates. Poisson's equation. Taylor series (statement only, no proof or

numericals). Elementary properties of Fourier series and Fourier transforms.

Laplace transformation of elementary functions, derivatives and integrals.

Convolution theorem. Applications to solution of ordinary differential

equations and simultaneous linear differential equations with constant

coefficients.

UNIT –V

Introduction to Univariate (normal, poisson and extreme value distributions)

and multivariate distributions. ANOVA, Regression analysis. Linear

discriminant analysis. Principle components analysis. Partial least squares.

21

Principle components regression. Support vector machines (No Numericals

for this unit). Markov chains. Hidden markov models. Viterbi algorithm,

Parametric estimation for HMM's (Baum-Welch and Viterbi training). EM

algorithm. (Numerical problems only for Markov chains).

Text Books:

1. E. Kreyszig. Advanced engineering mathematics. (Units-III,IV & V)

2. Higher Engineering Mathematics by Dr.B.S.Grewal. (Unit-I & II)

3. Intermediate Mathematics Volume I & II (Unit – I, V.Venkateswara Rao,

S.Chand& Company Ltd.

Reference Books:

1. Biological sequence analysis, Durbin, Eddy, Krogh and Mitchison (1998)

Cambridge University Press.

2. Ewens and Grant (2001) Statistical methods in bioinformatics: an

introduction. Springer verlag.

3. K.Lange. Mathematical and statistical methods for genetic analysis. 2nd

Ed.

(2003) Springer.

22


RESEARCH METHODOLOGY AND STATISTICAL METHODS


UNIT – I

Research Process: Introduction to research methodology, objectives,

classification of research methods: Historical method, case study method,

survey method, experimental method, and other methods( field investigation

research, evaluation research, auction research, ex-post facto research,

laboratory research, business game) – Definition, significance, sources,

advantages, limitations, steps involved in research.

Research Problem: sources, criteria of a good research problem, formulating

and stating the problem, common errors in selecting and formulating a

research problem.

Research Design: Definitions, need for a research design, characteristics of

good research design, components of a research design, types of research

design: descriptive, diagnostic, exploratory and experimental.

UNIT – II

Sampling Methods: Introduction of sampling, probability and non

probability sampling, sampling procedures – simple random, stratified,

systematic, cluster and multistage sampling, concept of sampling

distribution.

Collection and Processing of Data: Sources of data, methods of collection of

primary and secondary data, editing, coding, classification and tabulation of

data, graphical and representation of data, diagrammatic representation of

data.

UNIT – III

Inferential Statistics: Basics of Statistical Inference, Sampling distribution,

Estimation – Point estimation, Interval estimation, Parameter, Statistic,

Concept of a hypothesis, Research Hypothesis, Null Hypothesis, Level of

Significance, Comparison of means of two samples, Comparison of sample

proportion with population proportion, Comparison of two sample

proportions, Degrees of Freedom, Critical Value, Table value, Type I and

Type II errors, Rules for rejection & acceptance of Null Hypothesis,

Standard Error.

UNIT – IV

Inferential Statistics – Parametric and Non-Parametric Test: „t‟ test –

Comparison of sample mean with the population mean, Comparison of

means of two independent samples, Comparison of two correlated samples

23

„Z‟ test – different applications ANOVA – one way ANOVA: „F‟ test, Chi

square test.

UNIT – V

Correlation and Linear Regression: Introduction of correlation & regression

concepts, estimation of correlation coefficient, regression coefficients,

variance of sample estimates of the parameters, non linear regressions,

weighted and transformations in regression analysis, application of linear

regressions - standard curves in drug analysis and drug stability studies,

analysis of covariance.

Text books:

1. Santosh Gupta: “Research Methodology and Statistical Techniques”, Deep

& Deep Publication, 2001

2. K. P. C. Swain: “A Text book of Research Methodology”, 1st edition,

Kalyani Publishers, 2007.

Reference:

1. C.R.Kothari: “Research Methodology – Methods & Techniques”, 2

edition, Wishwa Prakashan, 2000.

2. “Research Methodology and Statistical Techniques” Indira Gandhi

National Open University.

24


PROTEIN CHEMISTRY / PROTEIN ENGINEERING


UNIT- I

Biomolecules. Chemical bonding. Structure and function of proteins.

Structure and role of amino acids in protein folding. Amino acids and

proteins classification, Structural organisation of proteins. Energy status of a

protein molecule.

UNIT – II

Protein folding - Hierarchic protein folding, - Defective protein folding,

- Molecular chaperones, - The HSP 70 chaperone system, - Proteasomes,

Prions, Polyketides and non-ribosomal peptides, - Combinational

manipulation of polyketides and non ribosomal peptides. Design and

construction of novel proteins and enzymes. Effect of amino acids on

structure of proteins

UNIT – III

Conformation of proteins in general and enzymes in particular. Classification

and functions of Enzymes. Architecture and functions of enzymes and

coenzymes involved in disorders. Structure function relations of enzymes.

Inborn errors of metabolism and the enzymes involved in it.

UNIT- IV

Physical methods such as x-ray crystallography for determination of protein

structure. Site directed mutagenesis for specific protein function. Basic

concepts for design of a new protein/enzyme molecule. Specific examples of

enzyme engineering.

UNIT- V

Protein prefractionation and sample preparation, Two dimensional

electrophoresis (2-D PAGE), Protein identification. Post translational

modification. Essential requirements for protein synthesis.

References:

Essential Reading :

1. J.L. Cleland and C.S. Craik, Protein Engineering: Principles and Practice,

Wiley-Liss, ISBN-13: 978-0471103547, 1 edition, February 7, 1996.

2. Biochemistry Lubert Stryer

3. Principles of Biochemistry Nelson & Cox

Supplementary Reading :

1. S. Lutz and U. T. Bornscheuer, Protein Engineering Handbook, Wiley-

VCH, New edition ISBN-13: 978-3527318506, January 20, 2009. D.

Balasubramaniam, Bryce, Dharmalingam, Green, Jayaraman Univ. Press,

1996

25


NANOBIOTECHNOLOGY


UNIT-I

Introduction to Nanotechnology: Size dependent properties. Size dependence

of sedimentation rate, adsorption effects, scattering of light, absorption of

electromagnetic radiation, electrical and magnetic properties. Effects of

confinement on protein stability.

UNIT II

Production of nanomaterials: Top down & bottom up strategies. Microbial

production. Thermodynamics and statistical mechanics of self-assembly and

template directed assembly: The Ising model. Cooperative transitions in

biological systems. Zimm-Bragg theory for polypeptides and base-pairing

between complementary strands of nucleic acids.

Vectors for drug delivery: Micelles, viral capsids and diatom skeletons.

Targeted drug delivery – Nanobioconjugates for receptor targeting and

magnetic guidance. Controlled drug release.

UNIT III

BioNanomaterial characterization: Electron microscopy. Force microscopy.

Light Scattering. Optical tweezers and optical molasses. Localized surface

plasmon resonance.

UNIT IV

Nanomaterials for Biomedical imaging: Quantum dots. Nanomaterials for

MRI. Magnetic resonance – principles, theory of relaxation, relationship

between size and relaxation properties.

Theranostics.

UNIT V

Diagnostics and Prognostics: Principles and applications of Nanoarrays and

Nanofluidics. Nanopore sequencing of DNA. BioNanomechanics:

NanoBiomotors. Mechanics of cilia and flagella. Nanobioelectronics:

Nanowires based on DNA. Molecular transistors. Voltage gated ion

channels.

Text books:

1. Neimeyer & Mirkin. Nanobiotechnology. Vol I & II.

2. Tuan Vo-Dinh. Nanotechnology in biology and medicine: Methods, devices

and applications. (2007) Taylor & Francis. (Distributed by IK.Publishers)

26

Reference books:

1. Vijay K. Varadan. Nanomedicine: Design and Applications of magnetic

nanomaterials, nanosensors and nanosystems. (2008). Wiley Dreamtech

India.

2. Robert Freitas. Nanomedicine. Vol. I Basic capabilities.

3. Patrick Abgrall, Nam-Trung Nguyen . Nanofluidics . 2009. Artech House.

ISBN 159693350X, 9781596933507

4. G.T. Hermanson. Bioconjugate techniques. 2008. Academic Press.

5. C.M. Niemeyer. Bioconjugation protocols: strategies and methods. In

Methods in molecular biology. 2004. Humana Press. Isbn 9781588290984.

6. Challa SSR Kumar. Nanosystem characterization tools in the Life Sciences

(2006). Wiley Dreamtech India.

27


BIOELECTRONICS (FREE ELECTIVE)

Course Code: EPRBT 127 Credits: 0 Hours: 3 per week

UNIT I

Neuromorphic systems - the RF cochlea. Concepts of Cytomorphic

electronics. Brain-machine interfaces. Information, noise, energy and power.

Connections between feedback loops and circuits. Scaling laws for power in

analog circuits. Introduction to Op-amps. Applications of Op-amps.

UNIT II

Low power transimpedance amplifiers and photoreceptors. Low power

transconductance amplifiers. Low power current mode circuits. Design of

Filters – low pass, high pass, band pass and band reject. Low power filters

and resonators. Convertors - A/D convertors, D/A convertors. Bionic ear

(Cochlear implants).

UNIT III

Biosensors and actuators. Direct electron transfer between enzymes and

electrodes. Modeling and simulation of enzyme electrodes. Hybridization

efficiency and sensitivity of oligonucleotide sensitive electrodes. Design

and construction of glucose biosensors. Design and applications of phenol

biosensors. Screen printing methods in biosensor production.

UNIT IV

Wireless inductive power links for medical implants. Energy harvesting RF

antenna power links. Thevenin equivalent circuit models of antennas. Near

field coupling. Far field coupling. Impedance matching. Rectifier

optimization.

UNIT V

RF telemetry: Impedance modulation in coupled parallel resonators.

Impedance-modulation receiver. Pulse-width modulation receiver. Energy

efficiency of the uplink and downlink. Scaling laws for power consumption

in impedance modulation links. Rf antenna links for implants.

28

Text books:

1. Rahul Sarpeshkar. Ultra low power bioelectronics: fundamentals,

biomedical applications and bio-inspired systems. (2010). Cambridge

University Press.

2. P.N.Bartlett. Bioelectrochemistry: Fundamentals, Experimental Techniques

and Application. John Wiley and Sons. (2008) (Chapter 8: Modeling

Biosensor responses).

3. R.B.Northrop. Analysis and Application of Analog Electronic Circuits to

Biomedical Instrumentation. 2nd

Edition. (2012) Taylor and Francis.

Reference books:

1. The art of electronics. Horowitz and Hill. Cambridge University Press.

2. Jonathan Cooper, Anthony Cass. Biosensors: a practical approach. 2nd

ed.,

Vol.268 of Practical approach series (2004). Oxford University Press.

3. Pethig, Ronald R. & Smith, Stewart. Introduction to Bioelectronics: For

Engineers and Physical Scientists. (2012). John Wiley and Sons.

Prerequisites:

1. Basic Electronics, Process dynamics and Control.

29


PHARMACOLOGY AND GENETIC ENGINEERING

LABORATORY


Minimum of 10 experiments from the following:

1. Determination of clotting time and effect of anticoagulant on coagulation

time.

2. Recording of systemic arterial blood pressure and effect of posture on blood

pressure.

3. Determination of lung volumes and capacities.

4. Recording of 12 lead ECG.

5. Study of simple muscle twitch (SMT).

6. Study of fatigue in skeletal muscle.

7. MTT assay for cell viability

8. Scatchard plots.

9. Plasmid isolation and Restriction.

10. Ligation.

11. Transformation of E.coli.

12. Construction and screening of a cDNA library.

13. DNA sequencing.

14. Molecular weight determination by electrospray Mass spectrometry.

15. Peptide mapping of proteins.

16. Edman sequencing of polypeptide.

17. Polypeptide sequencing using Mass spectrometry.

18. PCR.

19. DNA arrays for gene expression.

Note: If equipment for conducting experiments is not available, data obtained

from databases or simulation may be used.

Text book:

1. Molecular cloning. Vol.I, II and III. Sambrook, Fritsch and Maniatis.

30


FERMENTATION AND CELL CULTURE Laboratory


1. Production and isolation of penicillin

2. Production and isolation of streptomycin

3. Media and sterilization techniques for Plant tissue culture

4. Development of callus from explants of Catharanthus roseus

5. Extraction and isolation of vinblastine/vincrystine

6. Extraction of quinolone alkaloids from Cinchona officinalis bark

7. Media and equipment for Animal cell culture

8. Separation and culture of human lymphocytes

9. Maintenance of cancer and Haematopoietic cell lines and testing of

bioactivity of plant extracts on these cell lines

10. Production, isolation and/or Characterization of antibodies


SEMINAR

Course Code : EPRBT 113

Credits : 3 Hours: 3 per week

31

M.Tech. Biotechnology – II SEMESTER

PHARMACOINFORMATICS

Code : EPRBT201 Credits : 3 No. of hours: 3 per week

UNIT-I

Similarity score matrices (PAM, BLOSUM), sequence alignment using

dynamic programming – Needleman-Wunsch algorithm for global

alignment, Smith-waterman algorithm for local alignment, Multiple sequence

alignment – methods of multiple sequence alignment, multidimensional

dynamic programming, multiple sequence alignment by profile HMM

tranining.

UNIT-II

Molecular phylogenetics: introduction to binary trees. Phylogenetic tree

construction using weighted parsimony and neighbor-joining, Combined

multiple sequence alignment and phylogeny – Sankoff and Cedergren

method. Sequence graphs. Probabilistic models of evolution – Jukes cantor

model and Kimura model.

UNIT-III

Prediction of RNA secondary structure: Nussinov folding algorithm, energy

minimization and Zuker folding algorithm, covariance models. Introduction

to immunoinformatics. Principles of B-cell and T-cell epitope prediction.

UNIT-IV

Chemoinformatics: Pharmacology databases, structure databases, Molecular

descriptors. Molecular similarity. 2D substructure searching. 3D database

searching. Pharmacophore keys. SQL: Data definition, data manipulation and

control statements.

UNIT-V

Informatics based methods for prediction of pharmacokinetic properties:

ClogP, Intestinal membrane permeability, Blood-brain-barrier permeability,

toxicity. Integrated Models for prediction of absorption, distribution,

metabolism and elimination. One-compartment model, two compartment

models and multi-compartmental models.

Text books:

1. Biological sequence analysis. Durbin, Eddy, Krogh and Mitchison.

(Cambridge University Press). (For Units I,II and III)

2. AR Leach and VJ Gillet. An introduction to chemoinformatics. Springer.

(2007)

32

Reference books:

1. Clinical Pharmacokinetics: Concepts and Applications, M.Rowland and

T.N. Tozer, 3rd edition, Lea and Febiger, Philadelphia, 1995.

2. Molecular modeling, Principles and applications, Andrew R. Leach, 2nd

Ed.(2007) Prentice Hall (Unit IV)

3. Computational Molecular Biology: An algorithmic approach – Pavel,

A.Pevzner. (PHI)

4. Bioinformatics, D.Mount

5. Database Management systems: C.J.Date

6. A practical guide to the analysis of gene and proteins. Baxevanis. 3rd

Ed.

(2005) Wiley, (Unit IV and Unit V)

33


PROTEOMICS AND GENOMICS FOR TARGET IDENTIFICATION


UNIT-I

Protein expression profiles. Analysis of data from 2DGE experiments.

Analysis of data from Mass spectrometry: Peptide sequencing using mass

spectrometry -spectrum graphs. MS for protein identification via database

search. Spectral convolution. Spectral alignment.

UNIT-II

Protein function: Use of sequence patterns, motifs and profiles. Pattern

representation methods: consensus, regular expressions, profiles. Modeling

of metabolic pathways. Protein protein interactions: Methods (phage display,

yeast two-hybrid technique, protein arrays) and Tools for analysis of protein-

protein interaction.

UNIT-III

Gene prediction – frequentist approaches, model based approaches and

similarity based approaches. Genome assembly and annotation. Fragment

assembly. Mapping, Interval graphs.

UNIT-IV

Marker genes and polymorphism at the genomic level. DNA Microarrays for

detecting SNPs. Data and Algorithms for inference of gene regulatory

networks. Modeling of signal transduction pathways and Gene regulatory

networks.

UNIT-V

Comparative genomics: Genome alignment and Genome rearrangements.

Sorting by reversals. The breakpoint graph. Interleaving graphs and hurdles.

Duality theorem for genomic distance.

Text books:

1. S.R.Pennington and M.J.Dunn. Proteomics. Viva books. New delhi, 2002.

2. Hiroaki kitano. Foundations of sytems biology. Mit press. (2001)


Ed.(2006) Blackwell publishers.

34

References:

1. Computational Molecular Biology:An algorithmic approach– Pavel,

A.Pevzner (PHI).

2. Charles R. Cantor, Cassandra L.Smith (1999) Genomics: the science and

technology behind the human genome project. John wiley and sons (asia)

pvt. ltd. Singapore.

3. Kohane, IS., Kho, A and Butte, A.J. 2002. Microarrays for an integrative

genomics. Barnes and Nobles, MIT press.

4. T.A.Brown. Genomes. 2nd

edition. Bios scientific. 2002.

5. Villas-Boas. Neilsen. Smedgard. Hansen, Roessner-Tunali. Metabolome

analysis – an introduction.

6. Functional genomics. A practical approach. S.P.Hunt and R.Livesey. (IK

Publishers). 2004.

35


SCREENING AND TARGET VALIDATION


UNIT-I

Experimental methods for binding studies: Use of linear and non-linear

Scatchard plots for studies of ligand-receptor binding. The Hill plot. SPR.

UNIT-II

NMR. Chemical shifts, chemical exchange and relaxation. Use of NMR for

structure determination of small molecules – application of chemical shift, J-

coupling and relative areas. The Nuclear Overhauser effect. 2D and 3D NMR

spectroscopy principles. Structure determination of macromolecules and

complexes. Determination of binding sites for weakly interacting ligands.

Screening by NMR. Principles of MRI.

UNIT-III

X-ray crystallography for target and lead characterization. . Small molecule

structure determination using direct methods. Phase determination of large

molecules using MIR, MAD and molecular replacement. The Laue method.

Introduction to metabolic profiling. Experimental methods for Metabolic flux

analysis.

UNIT-IV

Combinatorial chemistry: Principles of combinatorial synthesis. Design of

combinatorial libraries. Measures of diversity of a combinatorial library.

Characterization of combinatorial libraries. High throughput screening. High

throughput screening for lead discovery. Tools for high throughput

screening. Assay technologies.

UNIT V

Uses of comparative genomics. Gene expression profiling for target

validation. Algorithmic approaches to clustering gene expression data. Gene

knockouts, Gene traps and gene knockdown in mice for target validation.

Animal models for important therapeutic areas.

Text books:

1. Biophysical Chemistry , Cantor and Schimmel (Unit-I and Unit-III)

2. R.Mannhold, H.Kubinyi, G.Folkers. High-throughput screening in drug

discovery in Methods and Principles in Medicinal Chemistry (2006). Wiley-

VCH (Unit IV)

36

3. O.Zerbe, R.Mannhold, H.Kubinyi and G.Folkers. BioNMR in drug research.

Methods and principles in medicinal chemistry. Vol. 16. (2006). Wiley-

VCH. (Unit II)

References:

1. B.W.Metcalf and S.Dillon. Target validation in drug discovery.(2006)

Academic Press.

2. Burger‟s Medicinal Chemistry, 6th

Edition, Vol.I and II (Unit-I, II, III,IV)

3. Villas-Boas. Neilsen. Smedgard. Hansen, Roessner-Tunali. Metabolome

analysis – an introduction (Unit III)

4. I.Pelczer. NMR in Ligand screening: Theory, methods and applications.

(2006). Oxford University Press.

5. N. Beckmann. In vivo MR techniques in drug discovery and development.

(2006). Informa healthcare.


Ed.(2006) Blackwell publishers. (Unit V)

7. Model Organisms in Drug Discovery by Pamela M.Carroll and Kevin

Fitzgerald (2003) (Unit V)

8. D.Leon and S.Markel. Insilico strategies in drug target identification and

validation.(2006). Drug discoveries series. CRC.

37


BIOLOGICAL PROGRAMMING: BIOPERL, JAVA AND BIOJAVA


UNIT-I

Perl : Variables, operators and functions. Regular expressions. Pattern

matching. Data structures. Arrays. Modules. Example programmes : Program

to find restriction sites, Program to convert genbank format file to Fasta

format.

UNIT-II

Bioperl : Bio::SeqIO class. Features and location classes. Alignment

analysis with blast and genscan. Database classes. Connecting to Databases.

Example programmes : Translate given DNA sequence to predict possible

polypeptides using BIOPERL, Program to convert genbank format file to

Fasta format using BIOPERL.

UNIT-III

Java: Objects and Classes. Classes declaration, Use of Math function, Java

Structure, Constants, Variables and Data Types, Decision making and

Branching, Classes, Objects and Methods.

UNIT-IV Applet Programming, Java applets. Graphics. Fonts. color. animation.

Graphics programming, Managing Input/Output files in Java.

UNIT-V

BioJava: Alphabets and symbols, Basic sequence manipulation, Translation,

Proteomics, Sequence I/O, Annotations, Locations and features, Protein

alignments, Genetic algorithms, Protein structure. Example Programmes:

Write a Biojava program to get all the Alphabets, DNA symbols and Protein

symbols.

Text books:

1. James D. Tisdall (2001) Beginning Perl for Bioinformatics. Oreilly and

Associates

2. Cynthia Gibas and Per Jambeck (2000) developing bioinformatics computer

skills. Oreilly and Associates.

3. Rex A Dwyer. Genomic Perl. Cambridge University Press.

4. Programming Perl by Larry Wall, Tom Christianson, Jon Orwant. Oreilly.

5. Programming with Java – A Primer by Balaguruswamy, Tata Mc Graw Hill,

New Delhi.

6. Java for Bioinformatics and Biomedical applications. H.Bal &

J.Hujol(2006) Springer.

38


ADVANCED INSTRUMENTAL METHODS OF ANALYSIS


UNIT I

The Transmission Electron microscope. Wavelength of electrons. Resolution

of the electron microscope. Collimation of electron beam. Image formation

and data analysis. Sample preparation. Vacuum requirements. The Scanning

Tunneling microscope. Atomic force microscopy. Scanning modes in AFM.

Magnetic force microscopy. Near field scanning optical microscope.

UNIT II

Microarrays: Types of microarrays. Fabrication of microarrays – Robotic

spotting and light-directed combinatorial systhesis. Microarray design and

Microarray data analysis. Applications of microarrays – SNP analysis,

differential expression, Diagnostics and Prognostics.

UNIT III

Microfluidics: Fundamentals of fluid mechanics in the micro- and

nanoscale. Electrokinetic effects in micro- and nanochannels. Zeta potential.

Mixing in microscale. Fabrication of microfluidic channels using glass,

silicon and polymers. Pumps, Valves and Sensors for microfluidic systems.

Microfluidics for diagnostic and prognostic applications. Lab-on-a-chip

devices. Integrated microfluidic circuits.

UNIT IV

Optical methods: Scattering: Rayleigh scattering. Use of scattering to obtain

particle number. Use of scattering to determine size distribution. Mie

Scattering. Raman scattering and resonance raman scattering.

Quantum dots – relationship between particle size and absorption properties.

Optical tweezers - Measurement of forces between nanoparticles with

optical tweezers.

UNIT V

Principles of magnetic resonance. Theory of relaxation. FTNMR. Spin echo.

Pulsed field gradients and Gradient echos. Principles of Magnetic resonance

imaging. MR angiography. MR-spectroscopy. Diffusion tensor imaging.

MR based reporter genes. MRI markers. MR based Theranostics.

Text books:

1. Challa SSR Kumar. Nanosystem characterization tools in the Life

Sciences (2006). Wiley Dreamtech India.

2. Patrick Abgrall, Nam-Trung Nguyen . Nanofluidics . 2009. Artech

House. ISBN 159693350X, 9781596933507

3. Principles of MRI. Brown and Venkatesan.

39


MOLECULAR DIAGNOSTICS


UNIT – I

Nucleic acid extraction. Nucleic acid amplification methods. Hybridization

based methods. Next-generation sequencing methods. Lab-on-a-chip

approach to molecular diagnostics.

UNIT – II

Quality control. Assurance. Identification and standards. Regulatory issues

in molecular diagnostics. Ethical considerations in molecular diagnostics.

UNIT – III

Molecular diagnosis for genetic diseases: Thrombofilia, Cystic fibrosis,

Huntington disease, X-linked mental retardation, Ataxias.

UNIT – IV

Molecular diagnostics for evaluation of cancer. Gene expression analysis

for tumor profiling. Molecular diagnostics for hematopoietic disorders.

Molecular diagnosis for cervical carcinoma.

UNIT – V

Molecular diagnosis for Hepatitis C Virus, Cytomegalovirus, multiple

respiratory syndrome virus. Molecular diagnostics for streptococcus and

tuberculosis. Molecular diagnosis for HLA typing.

Text books:

1. Molecular diagnostics: techniques and applications for the clinical laboratory. By Wayne W. Grody, Robert M. Nakamura, Frederick L. Kiechle

2. Fundamentals of molecular diagnostics. By David E. Bruns, Edward R. Ashwood, Carl A. Burtis. Elsevier Health sciences

40


TISSUE ENGINEERING


UNIT I

History and scope of tissue engineering. Organization of cells into higher

ordered structures. Composition and diversity of ECM, receptors for

extracellular matrix molecules. Matrix molecules and their ligands.

Dynamics of cell – ECM interaction and its relevance for tissue engineering.

UNIT II

Morphogenesis. Morphogenetic dynamics. Cell differentiation and

migration. Mechanical and chemical determinants of tissue development.

Engineering principles for the design of replacement tissues and organs.

Biomaterials for tissue engineering. Biomaterial scaffold properties. Effects

of pore size and interconnectivity. Surface modification of biomaterials.

UNIT III

Scaffold design and fabrication: Degradable polymers and Bioceramics for

tissue engineering. Principles of Scaffold design. Scaffold fabrication

technologies: Foaming, sintered microspheres, solvent casting, phase

separation, Electrospinning. Textile technologies for fiber and fabrics. Solid

free form fabrication.

UNIT IV

Bioreactors for tissue engineering: 2D and 3D cell culture. Bioreactors for

cell seeding. Bioreactors for enhanced mass transport. Kinetics and transport

in tissue engineering – molecular interaction with cells, molecular and cell

transport through tissue.

UNIT V

Tissue engineering for skin transplantation. Tissue engineering of musculo-

skeletal system (cartilage, bone, tendons and ligaments), cardiovascular

system (blood vessels and hear valves) and nervous system. Animal and

human trials of engineered tissues.

Text books:

1. Clemens A. van Blitterswijk, Peter Thomsen. Tissue engineering. Academic

Press series in biomedical engineering. Academic Press, 2008

2. Y. Ikada. Tissue engineering: fundamentals and applications. AP/Elsevier.

2006.

3. Challa SSR Kumar. Tissue, cell and organ engineering. Wiley-VCH. 2006.

4. PO Palsson and PA Bhatia. Tissue engineering. Prentice Hall 2004/Dorling

Kindersely 2009.

41


PHARMACOINFORMATICS LABORATORY

Code : EPRBT 211 Credits : 2 Hours: 6 per week

Use any available software for the following experiments:

Sequence alignment using Needleman-Wunsch method.

Sequence alignment using Smith-Waterman method.

Effect of scoring matrices and gap penalties on sequence alignment.

Multiple sequence alignment.

Use of HMM profiles.

Phylogenetic tree construction using parsimony.

Phylogenetic tree construction using UPGMA.

Phylogenetic tree construction using neighbor joining.

Displaying phylogenetic information

RNA secondary structure prediction.

Microarray data analysis.

Use of SQL: Database design for biological data. Data manipulation.

Queries, views and forms.

Databases:

Primary and Secondary Sequence and Structure databases: Organization of

data, contents and formats of database entries for major databases. Retrieval

of data using text-based search tools.

Metabolic pathways and Signal transduction pathways databases.

Bioinformatics resources at the species level.

Introduction to databases for proteomics.

Pharmacology databases.

Servers:

Use of servers for literature search, sequence search, multiple sequence

alignment, motif finding, gene prediction, genomic analysis, secondary

structure prediction.

42


BIOLOGICAL PROGRAMMING LABORATORY


Use Perl/Bioperl:

1. To convert sequence information between different formats.

2. To predict possible translations for a polynucleotide sequence.

3. For sequence alignment and

4. To create and access a local database.

Use Python/Biopython to display molecular structure.

Use of Java/BioJava to create a web-interface.

Write a program to implement:

Dynamic programming for sequence alignment – Needleman-Wunsch

algorithm

Dynamic programming for sequence alignment – Smith-Waterman

algorithm.

Phylogenetic tree construction using parsimony

Phylogenetic tree construction using neighbor joining.

Displaying phylogenetic information

Gene prediction.

Fragment assembly.

M.Tech. Biotechnology – II SEMESTER r

SEMINAR

Course Cod : EPRBT 213 Credits : 3 Hours: 3 per week

43

M.Tech. Biotechnology – III SEMESTER

MOLECULAR MODELING AND LEAD OPTIMIZATION


UNIT-I

Quantum chemistry for Modeling of small molecules: Variation method

and Time independent Perturbation theory. Ab initio methods for molecules:

Hartree-Fock SCF method. Introduction to UHF, electron correlation, CI

and density functional theory.

Introduction to semi-empirical methods: Huckel molecular orbital theory.

Pariser-Parr-Pople method. CNDO, AM1 and PM3.

UNIT-II Force fields for molecular modeling. Free energy calculations. Potentials of

mean force. Molecular surface area and solvent accessible surface area.

Solvation models – explicit water models, continuum models. Structure

function studies of the G-protein coupled receptors with emphasis on

adrenergic receptor.

UNIT-III Conformational analysis: Geometry optimization using steepest descent

and conjugate gradients. Distance geometry. Monte-carlo simulation.

Molecular dynamics and simulated annealing.

Prediction of transmembrane segments in membrane proteins.

Protein 3D structure prediction: Comparative modeling. Threading and Fold

prediction. Methods based on minimization of energy.

UNIT-IV Ligand based drug design: SAR, QSAR and 3D-QSAR. Partial least

squares and Molecular field analysis (COMFA). 3D-pharmacophores.

Deriving 3D pharmacophores (Constrained systematic search, Ensemble

distance geometry, Ensemble molecular dynamics, genetic algorithms, clique

detection, maximum likelihood).

UNIT-V

Receptor based drug design: Computational methods for identification of

plausible binding sites. Molecular Docking (rigid body and flexible

docking). Receptor based de novo ligand design. Text books:

1. Molecular modelling. Principles and applications. - Andrew R. Leach. 2nd

Ed.

(2007). Prentice Hall.

2. Structural Bioinformatics. Ed. P.E. Bourne and H.Weissig. (2003). Wiley-liss.

3. Molecular quantum mechanics. P. Atkins and R. Friedman. 4th

Ed. (2005).

Oxford University Press.

4. Poul Krogsgaard-Larsen et al. (2002) Textbook of drug design and discovery.

Taylor and Francis publishers.

44


MODELING AND SIMULATION OF DRUG MANUFACTURING

PROCESSES


UNIT-I

Mathematical modeling. Compartmental models. Models with memory.

Models with time delay. Parameter estimation. Model validation. Modelling

of dynamical systems. Stability of dynamical systems.

UNIT-II Modeling and simulation of Unit processes used in bulk drug manufacture:

Batch reactor and CSTR. Downstream processing calculations for

sedimentation, centrifugation, solvent extraction, distillation, adsorption,

crystallization. Environmental assessment and Economic assessment.

UNIT-III

Tablet manufacture: Machine theory, design and process troubleshooting of

tablet compression. Modeling and simulation of granulation scale-up.

Modeling and simulation of coating. Modeling and simulation of packaging

techniques.

UNIT-IV Introduction to Good manufacturing practices (GMP). Biosafety: Process

safety and reaction hazard assessment. Criticality classes. Reaction heat,

adiabatic temperature rise, MTSR, gas evolution. Safety testing. Risk

assessment of biological hazards.

UNIT-V Pilot plant design. Fermenter design calculations. Pilot plant operation

(simulations). Plant design calculations for the Penicillin production system.

Plant design calculations for production of insulin.

Text books:

1. Leon Lachman et al – Theory and practice of industrial pharmacy. 3rd

edition.

Lea and Febiger, 1986.

2. Encyclopedia of Pharmaceutical Technology. 3rd

ed.(2006). Informa Healthcare.

3. Chemical Engineering in the pharmaceutical industry: from R&D to

manufacturing. Ed. David J. am Ende. Chapter 11. Process safety and reaction

hazard assessment. John Wiley and Sons, 2011.

Reference:

1. Good manufacturing practices for pharmaceuticals. 6th

edition.(Drugs and

pharmaceutical sciences. (2006). Informa Healthcare.

45


MOLECULAR MODELING LABORATORY


1. Generating 3D representations from 2D descriptions of small

molecules.

2. Use of molecular mechanics for geometry optimization of a small

molecule.

3. Evaluate energy of a small molecule using

CNDO/MINDO/MNDO/AM1/PM3

4. Evaluate energy of a small molecule using ab initio QM with 631G

basis set.

5. Calculate solvent accessible surface area.

6. Polypeptide conformational analysis using monte-carlo and molecular

dynamics methods.

7. Secondary structure prediction. Servers: PHD, PSIPRED

8. Prediction of transmembrane helices.

9. Comparative modeling of a small protein.

10. Docking of a polypeptide ligand into a protein.

11. QSAR.

12. 3D-QSAR.

13. CoMFA.

14. SXRs for ADMET.

46


MODELING AND SIMULATION LABORATORY


1. Modelling of dynamical systems. Parameter estimation. Simulation.

Stability of dynamical systems.

2. Modeling of metabolic pathways. Comparison of metabolic pathways.

3. Modeling of signal transduction pathways and networks.

4. Whole cell simulations.

5. Representation of signal transduction pathways using Systems biology

markup language.

6. Ease of formulation.

7. Modeling and simulation of bioprocesses:

8. Biotransformation of drugs, microsomal and non-microsomal

mechanisms.

9. Factors influencing enzyme induction and inhibition.

10. Modeling and simulation of unit operations used in bulk drug

manufacture.


PROJECT



INDUSTRIAL TRAINING REPORT

Course Code: EPRBT 314 Credits : 2

M.Tech. Biotechnology – IV SEMESTER

PROJECT


Documents

M.tech Biotechnology Final 2012-13 (New)