1. Overview of Biotechnology Week 1&2 (12&19 Sept 2013) Mdm Khadijah Hanim Abdul Rahman School of Bioprocess Engineering, UniMAP khadijahhanim@unimap.edu.my

2. Course Outcomes (C0s): Ability to explain foundations of modern biotechnology. Ability to demonstrate important recent advances in methods and applications of biotechnology with regards to microorganisms and plants. Ability to differentiate scopes and importance of various biotechnological streams. Ability to demonstrate understanding on ethical implications of biotechnology.

3. Evaluation Peperiksaan/ Examination: 60% Mid-term Examination 1 = 10% Mid-term Examination 2 = 10% Final Examination = 40% (ii) Kerja kursus/course work: 40% Assignments & Quizzes = 40% (Quizzes may be given without prior notice)

4. List of text books and references : Text Book: William J.T. and Michael A.P. (2009). Introduction to Biotechnology. 2 nd Edition. Pearson Benjamin Cummings.

5. References Books: 1). Susan R. Barnum. (2005). Biotechnology an introduction. 2 nd edition. Thomson, Brooks/Cole Publication. 2). Acquaah, G. (2004). Understanding Biotechnology. Pearson. Prentice Hall. 3). Bougaize, D., Jewell, T.R. and Buiser, R.G. (2000). Biotechnology; Demystifying the Concept. Benjamin-Cummings Publication 4). Rene Fester Kratz PhD, Donna Rae Siegfried. (2010). Biology For Dummies. Second Edition. 5). R.C. Sobti and Suparna S. Pachauri (2009). Essential of biotechnology. CRC press, US.

6. Minggu/WeekKandungan Kursus / Course Contents (Panduan/Guidelines) Pensyarah/Lecturer Week 1-2 (9 Sept- 22 Sept) An Overview of Biotechnology Define biotechnology and describe the classical biotechnology and the foundations of new biotechnology. Express the importance and commercial potential of biotechnology. Mdm Khadijah Hanim Week 3-5 (23 Sept- 13 Oct) Techniques in Biotechnology Demonstrat e the basic principles of Recombinant DNA Technology and illustrate other methods used in biotechnological field, to include tissue culture, electrophoresis, Polymerase Chain Reaction (PCR) and biosensor. Mdm Khadijah Hanim Week 6 (14 Oct-20 Oct) Cuti Pertengahan Semester/ Mid-term Break Week 7-8 (21 Oct- 3 Nov) Biotechnology and Industry Illustrate scopes of industrial biotechnology and examine commercial production of microorganisms and product from microorganisms. Mdm Khadijah Hanim Week 9 (4 Nov-10 Nov) Biotechnology and Medicine Illustrate scopes of medical biotechnology and examine gene transfer methods, gene therapy and Human Genome Project (HGP) and applications. Mdm Khadijah Hanim Week 10 (11 Nov- 17 Nov) Biotechnology and Environment Illustrate scopes of environmental biotechnology and examine methods and application of microbial in bioremediation and wastewater treatments. Mdm Khadijah Hanim Week11-12 (18 Nov- 1 Dec) Biotechnology and Agriculture Illustrate scopes of plant biotechnology and methods of tissue culture used in biotechnology. Differentiate products produced through application of plant genetic engineering methods in crop improvement, herbicides resistance and insect resistance. Mdm Khadijah Hanim Week 13 (2 Dec- 8 Dec) Recent Advances in Biotechnology Demonstrate new development and findings in various fields of biotechnology. Mdm Khadijah Hanim Week 14-15 (9 Dec-22 Dec) Patents and Ethical Issues Describe the concept of patents. Illustrate public concerns and risk associated with genetic engineering, ethical, legal and social implications of biotechnology. Mdm Khadijah Hanim Week 16 (23 Dec-29 Dec) Minggu Ulangkaji/ Study Week - Week 17 – 19 (30 Dec-10 Jan) Final Examination -

7. What is Biotechnology? Have you ever? Vaccine/ use antibiotics Yogurt drink/cheese/tempeh Make a bread Received tissue grown from embryonic stem cells/ see n a ‘knocked out’ mouse/using insulin to treat diabetes

8. Definitions Using living organisms or product of living organisms for human/surrounding benefits To make products or to solve problems Biotechnology

9. Is biotechnology a new science? Gene cloning/ genetic manipulation – modern day techniques; BUT Many applications represent old practices with new methodologies. Microorganisms have been used in fermentation of bread, cheeses, yogurts, alcoholic beverages.

10. Fermentation alcohol During fermentation- yeast decompose sugar to derive energy Produce ethanol as waste Bread Yeast is added to make dough rise Yeast ferments sugar releasing CO2 – dough rise and creates holes Alcohol produced- evaporated when baked

11. Yeast for baking, wine & beers http://www.wellesley.edu/Chemistry /Chem101/alcohol/alcohol.htm Sumerian tablet recipe for beer 3200 BC Ancient Egyptians diet included bread & beer Chinese use of fermentation using beneficial bacteria to flavor and preserve food. Aztecs make cakes from Spirulina algae. 5000 year old bread http://www.touregypt.net/featurestories/brea d.htm

12. Selective breeding To improve production of crops and livestock = food Organisms with desirable features are purposely mated to produce offspring with the same desirable traits. Choosing organisms with useful genes and taking advantage of their genetic potential for human benefit.

13. Antibiotics Alexander Fleming discovered Penicillium mold inhibit the growth of bacterium Staphylococcus aureus (causes skin disease). Use to treat bacterial infections in humans.

14. Birth of modern biotechnology Since 1960s, rapid development and understanding in genetics and molecular biology – led to new applications and innovations in biotechnology. Gene cloning- ability to identify and reproduce gene of interest Genetic engineering- manipulating the DNA of an organism – recombinant DNA technology.

15. Biotechnology: A science of many disciplines

16. Summary of interdisciplinary nature in biotechnology E.g: Identify potential genes or gene products in bacteria for treating disease Basic science: - Biology - Microbiology etc To better understand the role of these genes Biochemistry Molecular biology genetics To study the DNA and protein data Gather information Computer science Statistics mathematics Drug testing Immunology Human, animal/plant physiology Chemical engineering physics production

17. Biotechnology ModernBiotech ClassicalBiotech Genomics RecombinantDNA MicrobialBiotech PlantBiotech AnimalBiotech MarineBiotech Immunology MedicalBiotech Forensic Fermentation Breeding Restriction enzymology Cloning Microarrays/GENE CHIP Human Genome Project Functional genomics PROTEOMICS CANCER RESEARCH GENE THERAPY THERAPEUTIC CLONING STEM CELLS HUMAN DEFENCE SYSTEM VACCINESANTIBODIES FOOD BIOTECH ENZYMOLOGYANTIBIOTICSFUELSBIOPOLYMERSAGRICULTUREBIOREMEDIATION TISSUE CULTURE GENETICALLY MODIFIED MEDICIANL TRANSGENICSAGRICULTURE FISH BIOTECH NATURAL BIOPRODUCTS ANIMAL HUSBUNDARY CROP IMPROVEMENT HIGHER YEILD HIGHER RESISTANCE CHEESEBEERWINEBREADYOGHURT DNA FINGER PRINTING CRIMINIAL PROFILING CRIME SCENE INVESTIGATION

18. Domestication of animals and cultivation of plants Artificial selection of genetic variation or selective breeding 8000-1000BC Evidence since 8000-1000BC Eg maize, rice, wheat, palms, dogs, horses, camels,oxens Prehistoric attempts by ancient ancestors to manipulate genetic composition of useful species. Historical development of Biotechnology

19. Herbs for medicine ancient vaccines Saffron- stigmas of the flower Crocus sativus Cumin seeds have a distinctive bitter flavor and strong, warm aroma due to their abundant essential oil content. Their smell can also be detected in the eater's sweat even after consuming only small amounts. It is used as an ingredient of curry powder. In herbal medicine, cumin is classified as stimulant, carminative, and antimicrobial Tumeric And the ancient Chinese first inoculated people with a weakened strain of the smallpox (variola) virus to prevent further infection

20. Why was Mendel's work not appreciated b4 1900? 1850-1900 birth of modern genetics Charles Darwin Origin of species Gregor Mendel Principles of Inheritance in pea plants 1900 1850 1866 1859 Carl Correns, Hugo de Vries & Tschermak Rediscovery of Mendel’s work. Beginning of modern genetics 1900 Natural selection. How does the variation that drives evolution get transmitted? If Darwin had considered Mendel's work he would have an available answer. Darwin did receive Mendel's paper but was unread (unopened).

21. Gregor Johann Mendel father of classical genetics Heinzendorf Central Europe Augustinian monk 1856 Developed the theory of inheritance Demonstrated with statistical data from crossing Pisum sativum Suggested that every cell contained pairs of ‘factors’ and that each pair determine specific traits (law of segregation) Unappreciated (due to lack of understanding in cell structure and cell division), but rediscovered 1900 Experiments in plant hybridization

22. Chromosomal theory of inheritance Chromosomes discovered in early 20 th century Epigenetic interpretation was further established Inherited traits are controlled by genes They reside in chromosomes These traits are faithfully transmitted through gametes (reproductive cell) to future individuals in the next generation Thomas Hunt Morgan

23. 1900-1950 cell biology, chromosomes, the search for genetic material 1900 1950 Stevens & Wilson Sex chr XX: female XY: male 1902 1908 Archibald Garrod Inborn errors of metabolism ‘one mutant gene-one metabolic block’ Due to lack of specific enzyme (albinism & alkaptonuria) 1944 Avery, MacLeod & McCarty Purified the transforming principle found to be DNA 1945 Max Delbruck Bacteriophages NB Nucleic acid was 1 st discovered 1869 by Friedrich Miescher obtained from pus 1910 Thomas H Morgan Chr theory of inheritance X linked inheritance Fly lab (Sturtevant) Linkage analysis Barbara McClintock Jumping genes Colour variation in Maize Transposable elements Erwin Chargaff A:T, G:C ratio 1 st antibiotic Penicillin discovered by Alexander Fleming Howard Florey 1928 1919 term biotechnology used fro the 1 st time Karl Ereky

24. Paul Berg & Herb Boyer 1 st recombinant DNA molecules 1972 Francis Crick & James Watson Solved double helix structure of DNA 1953 1950-1980 The code breakers 1950 1980 1970 1960 Smith & Wilcox 1 st restriction enzyme Hind III 1970 1951 Rosalind Franklin X-ray diffraction photos of DNA 1952 Martha Chase & Alfred Hershey Proof that DNA is Molecule of heredity 1977 Fred Sanger DNA sequencing Boyer Human Insulin from bacteria 1978 Genentech Monolconal antibody 1975 Kohler and Milstein. The dawn of biotechnology

25. 1960s-1980s L-Dopa as a therapeutic agent1960's Olah Hornykiewicz, who originally discovered that Parkinson's disease - development of L-Dopa as a therapeutic agent while working in Toronto. 1961 Discovery of the hematopoietic stem cell by Toronto researchers monoclonal antibodies1975 George Kohler and Cesar Milstein show that fusing cells can generate monoclonal antibodies. human insulin 1982 First genetically engineered product - human insulin produced by Eli Lilly and Company using E. coli bacteria - is approved for use by diabetics.

26. 1980-2000 1980 1990 2000 Kary Mullis PCR 1985 Olson, YAC 1987 1989 Francis Collins Lap Chee Tsui Identified gene CFTR (cystic fibrosis) Human Genome project Embryonic stem cells 1998 GM corn, FlavrSavr tomatoes 1994 Breast cancer gene Bcl-1, Bcl-2 Obesity gene Apoptosis gene etc identified Wilmut Clones Dolly 1997 Gene therapy trial Automated DNA Sequencing machine Caltech & ABI 1986 Check timeline Huntington's disease Linked to marker Gusella Announcement of HGP completion Collins & Venter Alec Jeffreys DNA fingerprinting 1984

27. 2000-2010 2000 2005 2010 Glofish 2003 GM zebrafish Preimplantation genetics Francis Collins Lap Chee Tsui Identified gene CFTR (cystic fibrosis) Human Genome project Breast cancer gene Bcl-1, Bcl-2 Obesity gene Apoptosis gene etc identified Gene Chip Gene control of development in Drosophila Personal genome Sequencing $1000 Rice genome seq-2002 1986 Check timeline Personalised medicine Announcement of HGP completion Collins & Venter

28. Products of modern biotechnology Currently- product related to human health Pharmaceutical products: drugs, vaccines and diagnostic kits 1 st biotechnology product: in 1982,Genentech: recombinant insulin for diabetes. Many products created by gene cloning: recombinant protein. Future trends: gene therapy (treat and cure human disease)

29. Production of recombinant protein

30. Types of biotechnology MicrobialAgriculturalanimal ForensicBioremediationAquatic medicalregulatory

31. Microbial Biotechnology Microbial Biotechnology – manipulation of microorganisms such as yeast and bacteriaMicrobial Biotechnology – manipulation of microorganisms such as yeast and bacteria ▫Create better enzymesCreate better enzymes ▫More efficient decontamination processes for industrial waste product removalMore efficient decontamination processes for industrial waste product removal ▫Used to clone and produce large amounts of important proteins used in human medicineUsed to clone and produce large amounts of important proteins used in human medicine Aspergillus niger Saccharomyces cerevisae

32. Agriculture Agricultural Biotechnology ▫Genetically engineered, pest-resistant plants, drought resistance, cold-tolerant. ▫Foods with higher protein or vitamin content ▫Drugs developed and grown as plant products- molecular pharming (tobacco is a non food crop- to produce recombinant proteins in their leaves)

33. Animal Animal Biotechnology ▫Animals as a source of medically valuable proteins  Antibodies (treatment for patients with immunity disorder)  Transgenic animal: secreted therapeutic proteins in their milk. Produced in large scale. ▫Animals as important models in basic research  Gene “knockout” experiments ( 1 or more genes are disrupted- to study the function of a gene)  Design and testing of drugs and genetic therapies ▫Animal cloning  Source of transplant organs

34. 1. Cloning requires an egg cell, and an adult donor cell. The (unwanted) chromosomes are removed from the egg cell and discarded. The nucleus, containing the DNA to be cloned, is removed from the donor cell. 2. The donor nucleus is inserted into the empty egg cell, a process called somatic cell nuclear transfer (SCNT). Afterwards the egg contains a full (adult) set of chromosomes as if it had been fertilised normally. 3. A pulse of electricity, or a chemical 'shock', kick-starts the development process, and the embryo begins to grow. 4. Cell division begins. The subsequent development of the embryo depends upon how successfully the donor nucleus has 're-programmed' the egg.

36. Forensic Forensic Biotechnology ▫DNA fingerprinting- method for detecting an organism’s unique DNA pattern  Inclusion or exclusion of a person from suspicion based on DNA evidence  Paternity cases  Identification of human remains  Endangered species  Tracking and confirmation of the spread of disease ie E. coli, AIDS, meningitis etc.

37. Bioremediation ▫The use of biotechnology to process and degrade a variety of natural and manmade substances  Particularly those that contribute to pollution ▫For example, bacteria that degrade components in crude oil  1989 Exxon Valdez oil spill in Alaska

39. Aquatic Aquatic Biotechnology ▫Aquaculture – raising finfish or shellfish in controlled conditions for use as food sources  30% of all fish consumed by humans worldwide ▫Genetic engineering  Disease-resistant strains of oysters  Vaccines against viruses that infect salmon and other finfish ▫Rich and valuable sources of new genes, proteins and metabolic processes with important applications for human benefits  Marine plankton and snails found to be rich sources of antitumor and anticancer molecules

40. Medical Medical Biotechnology ▫Involved with the whole spectrum of human medicine  Preventive medicine  Diagnosis of health and illness  Treatment of human diseases ▫New information from Human Genome Project  Gene therapy ▫Stem cell technologies

41. Medical Medical Biotechnology

42. Regulatory Regulatory Biotechnology ▫Quality Assurance (QA)  All activities involved in regulating the final quality of a product ▫Quality Control (QC)  Part of QA process that involves lab testing and monitoring of processes and applications to ensure consistent product standards

43. Biological Challenges of the 21 st Century How will medical biotechnology change our lives in the years ahead? ▫Human Genome Project  Research on the function of human genes and controlling factors that regulate genes ▫Human proteome  Collection of proteins responsible for activity in a human cell

44. Biological Challenges of the 21 st Century How will medical biotechnology change our lives in the years ahead? ▫Single Nucleotide Polymorphisms (SNPs)  Single nucleotide changes (mutations) in DNA sequences that vary from individual to individual  These variations influence how we respond to stress and disease and are the cause of genetic diseases  Arthritis, stroke, cancer, heart disease, diabetes, and behavioral and emotional illnesses

45. Biological Challenges of the 21 st Century

46. How will medical biotechnology change our lives in the years ahead? ▫Pharmacogenomics is customized medicine  Tailor-designing drug therapy and treatment strategies based on the genetic profile of a patient ▫Metabolomics  A snapshot of the small molecules produced during cellular metabolism  Glucose, cholesterol, ATP, and signaling molecules

47. Biological Challenges of the 21 st Century How will medical biotechnology change our lives in the years ahead? ▫Nanotechnology  Applications that incorporate extremely small devices  Small particles that can deliver drugs to cells

48. Biological Challenges of the 21 st Century

49. How will medical biotechnology change our lives in the years ahead? ▫Regenerative medicine  Genetically modifying stem cells of patients to treat genetic disease conditions

50. The Biotechnology Workforce Biotechnology is a global industry ▫Generates more than $63 billion in worldwide revenues ▫$40 billion in sales of biological drugs in the United States

51. The Biotechnology Workforce Jobs in Biotechnology ▫Research and development ▫Operations, biomanufacturing and production ▫Bioinformatics ▫Quality assurance and quality control ▫Clinical research and regulatory affairs ▫Marketing, sales, finance, legal

52. The Biotechnology Workforce