THE UNIVERSITY OF

GENERAL DESCRIPTION Perugia is a hill-town situated in the centre of , in a valley between and Rome. Its University was founded in 1308 by a Papal “Bulla” of Pope Clemente V. The "Studium Generale" was very famous in the XIVth century. It was in fact considered one of the most important Schools in Italy. Before the Clementine “Bulla” the Grand Council of Perugia's municipality, with the 1275 and 1276 deliberations, invited the students to come to Perugia to listen to the "reading of the laws", grammar, logic and other arts. The prestige of the "Studium" in the XIV century is connected above all with the following important personages: Cino da Pistoia, Bartolo da Sassoferrato and Baldo degli Ubaldi in Juridical Studies, Gentile da Foligno, Bartolomeo da Varignana and Tommaso del Garbo in the Faculty of Medicine and Surgery. The Law School was founded in Perugia by Bartolo and Baldo and continued in the XV and XVI centuries. During this time studies in Medicine were neglected: a document dated 1366 illustrates how direct observation on the cadaver was practised at that time. This tradition of anatomical studies was revived in the XVIII Century by Alessandro Pascoli. Worthy of note, as regards the teaching of Sciences, is that friar Luca Pacioli was a teacher of mathematics in the XV century and in the XVII Giuseppe Neri was a friend of Galileo. In the humanist sector, the Institution of the chairs in Greek and Hebrew should be remembered. During the second half of the XVIII Century there were a lot of political and social disorders that gave rise to enormous changes in thought and culture. Between 1799 and 1814, during the period of republican regime, the underwent many reforms. After the Napoleonic events, the "Consulta Straordinaria" of the Roman States introduced the system of studies practised in France, in Perugia. The "Consulta" plan organised the University into five Faculties with a Rector at the head instead of a Bishop and the Faculty Council was on the lines of the French model which, with many changes, still exists today. In 1814 Papal rule was re-established and reinforced by the 1824 “Bulla” of Pope Leone XII. With the reunification of Italy, in 1860, the General Commissary for Umbria, Gioacchino Pepoli, reorganised Perugia University. The University was declared a free University, administered by the Municipality and the Rectors who could formulate the statutes, with the approval of the Government. In 1925, the Faculty of Medicine and Surgery was completed. In 1927 the Faculty of Political Science was founded. Between 1935 and 1936, with the reunification of higher studies, the Faculty of Veterinary Medicine was reinstated and the Agricultural Faculty expanded by the aggregation of the Royal Institute for Agriculture which had been founded in Perugia in 1896. In the period following World War II Perugia University has developed greatly and at present there are the eleven Faculties which follow: LAW, POLITICAL SCIENCES, ECONOMICS AND BUSINESS STUDIES, LITERATURE AND PHILOSOPHY, ARTS, MEDICINE AND SURGERY, NATURAL, PHYSICAL AND MATHEMATICAL SCIENCES, PHARMACY, AGRICULTURE, VETERINARY MEDICINE, ENGINEERING. Many Faculties also included many degree of first level, PhD courses and Specialization Schools. There are also many inter-facultate courses in different disciplines including the International Degree course “Job Creation Oriented Biotechnology”.

HEALTH AND INSURANCE By law, Italian students are covered by a compulsory health insurance scheme administered by the regional health services. Guest students from EC countries, being included under their national health insurance scheme, are entitled to receive in Italy the health services of the A.S.L (Azienda Sanitaria Locale) by exhibiting the form issued by their Local Health Authority. Foreign students having scholarships from the Italian Government are given life, accident, and health insurance coverage for the duration of their stay in Italy. Moreover, all duly registered students, in particular ERASMUS and ECTS students, are insured against accidents which could happen at the University during experiments or practical activities indicated in the planned curriculum and carried out under the super-vision of professors, lecturers or assistants. HOW TO REACH PERUGIA

Perugia can be reached by the ROMA-FLORENCE or ROMA-ANCONA railway lines. Coming from the north: (from Florence) stop at Terontola and take the TERONTOLA- PERUGIA-FOLIGNO train. For those arriving from the Adriatic, take the: ANCONA-FOLIGNO-PERUGIA line. Rapid trains leaving Roma Central Station (Stazione Termini) to Firenze or to Foligno reach Perugia after 2 hours. One can reach Perugia by car, on the Roma-Milano motorway, or on the E7 Highway which crosses Umbria. A bus line connects Roma (Stazione Tiburtina- 7.15 a. m. , 8.15 a.m.-4 p.m., 6 p.m., 7 p.m.) with Perugia (P.zza Italia) in about two hours. There is an airport, the S. Egidio Regional Airport, 12 km. from Perugia - tel. 0756929447. Two flights connect Perugia to Milan daily and vice versa except during weekends. Leonardo Da Vinci Airport at Fiumicino (Rome) is 230 km. from Perugia. Daily connections to and from Perugia are available by coach ACAP-SULGA line (6.33 a.m. and 8 a.m., 9a.m.) - (tel. 0755009641). The Galileo Galilei Airport of Pisa is about 230 km. from Perugia. The Miramare Airport of Rimini is about 223 km from Perugia.

USEFUL ADDRESSES (telephone code number for Perugia is :075.

The University of Perugia Office for International Relations Libraries: the Central University library (a State Address: Piazza Università, 1 Address: Piazza Università,1 Institution) is located in the central building of the 06100 PERUGIA - ITALIA 06100 PERUGIA - ITALIA University of Perugia - P.zza dell'Università n. 1 Tel. 0039/075/5851 Tel. 0039/0755852093 tel. 5852140. It was founded in 1780 (ex Biblioteca degli Fax 0039/075/5852067 Tel. 0039/0755852176 Olivetani), holds more than 300.000 books and 900 Internet address: http://:www.olympus.unipg.it Fax 0039/0755852081 magazines. The Medical University library is located in the E-mail:[email protected] building of "Accademia Anatomico Chirurgica" - Via del A.D.I.S.U. ( Agenzia per il Diritto allo Studio Universitario: Giochetto, Perugia - Tel. 5735665. Address: Via Benedetta,14 Police Station (Questura di Perugia): Italian Language courses for Foreigners: Tel. 0039/0754691 Address: Via Cortonese,157 Address: Università Italiana per Stranieri - Palazzo Tel. (+) 39/07550621 Gallenga. P.zza Fortebraccio 4, 06100 Perugia Emergency telephone (police, ambulance etc.): 113 Tel. (+)39/07557461 - Fax 0755732014. Local Health Service: (Azienda Sanitaria Locale) First Aid Medical Service: Ospedale Policlinico Address: Via dei Filosofi, 9 - Perugia Sport and recreation: C.U.S. (Centro Universitario Monteluce Tel. (+)39/0755781 Sportivo) provides opportunities for many competitive Address: Via Bonacci Brunamonti Red Cross: (Croce Rossa) activities (athletics, rugby, canoe, volleyball, karate, judo, Tel. (+)39/0755781 Address: Via Bonacci Brunamonti bowling) or at non-competitive levels (football, 5 a side Tel. (+) 39/0 75/5781 football, basket, tennis, swimming). Information: Via Tuderte 10 - P.O. Box 69 - 06100 Perugia - tel. 07532120 - Fax 07530955.

♦ Bookshops: scientific and medical books (Italian or English) can be purchased at several shops in the historical centre of the town. ♦ Tourist Information Service: Piazza IV Novembre - 06100 Perugia tel. 0755041 - Fax 075504283. ♦ Local Newspapers: Corriere dell'Umbria (daily) Other information about Umbria can be found in special pages of national newspapers such as Messaggero, Nazione, etc. ""JJoobb CCrreeaattiioonn OOrriieenntteedd BBiiootteecchhnnoollooggyy"" IInntteerrnnaattiioonnaall FFiirrsstt LLeevveell DDeeggrreeee PPrrooggrraamm ooff tthhee CCoouurrsseess

WORK PLAN OF THE FIRST YEAR 2002/2003

1st semester Timetable 2nd semester Timetable General Inorganic Chemistry 16th – 30th September Biochemistry 3rd – 26th February Organic Chemistry 1st – 18th October Cell Biol. & General Histology 27th February – 17th March Computer Biostatistic 21st – 31st October Biophysics 18th – 28th March Physics 4th – 22nd November Plant and Human Physiology 31st March – 21st April Bioethics 25th November – 3rd December Instrumental Analysis 10th April – 2nd May Current Topic 4th – 13th December Current Topic 5th – 9th May Christmas Holiday 16th December – 10th January Examination 13th – 31st January Examination 12th –16th May Stages * 01 June – 30 August

*STAGES OF 3 MONTHS: EACH STUDENT WILL RECEIVE THE AMOUNT OF 1.000 EURO FROM THE LOCAL AUTHORITY OF PROVINCE OF

PERUGIA

WORK PLAN OF THE SECOND YEAR 2002/2003

3° semester Timetable 4° semester Timetable Immunology 16-30 September Pharmacology & Toxicology 03-14 February Cell Culture 01-04 October Biotechnological Processes 17-28 February Molecular Biology 07-25 October Molecular & Genetic Diagnostics 03-17 March Genetics 28 October-15 November Current Topic 18-21 March Microbiology and Virology 18 November – 06 December Pharmaceutical Biotechnology & 24 March- 04 April Drug Engineering- optional Current Topics 09-13 December Animal Biotechnology & 24 March- 04 April Christmas Holiday 16 December Tissue Engineering- optional Examination 13-31 January Plant Biotechnology – optional 07-18 April Food Processing – optional 07-18 April Bioprocess & Bioengineering Fundamentals- optional 07-18 April Examinations 10-15 May Stages * 01 June – 30 August

*STAGES OF 3 MONTHS: EACH STUDENT WILL RECEIVE THE AMOUNT OF 1.000 EURO FROM THE LOCAL AUTHORITY OF PROVINCE OF

PERUGIA AND THEY WILL ALSO RECEIVE 15 CREDITS For further information the students can also consult the Special Edition of

Biotechnology Thematic Network Newsletter on: http://www.krenet.it/biotech

I YEAR

I SEMESTER II SEMESTER

MODULES EBT 1 Hrs. Hrs. CREDITS MODULES EBT 1 Hrs. Hrs. CREDITS Lecture Practice Lecture Practice General and EBT 1-01 20 40 7 Biochemistry EBT 1-07 25 45 7 Inorganic Chemistry Organic EBT 1–02 25 50 8 Cell Biology & EBT 1-08 25 45 7 Chemistry General Histology

Computers & EBT 1–03 15 30 5 Biophysics EBT 1-09 14 26 4 Biostatistics Physical and EBT 1–04 25 50 7 Plant and Human EBT 1-010 14 26 4 mathematical Physiology fundaments for biotechnology Bioethics EBT I-05 10 20 2 Instrumental EBT 1-011 24 46 7 Analysis

Current Topic I EBT 1-06 5 10 1 Current Topic II EBT 1-012 4 6 1 (every semester) (every semester) Summer Stage 15

II YEAR

III SEMESTER IV SEMESTER

MODULES EBT 2 Hrs. Hrs. CREDITS MODULES EBT 2 Hrs. Hrs. CREDITS Lecture Practice Lecture Practice Immunology EBT 2-01 18 36 5 Pharmacology & EBT 2-07 20 40 6 Toxicology Cell Culture EBT 2-02 7 14 3 Biotechnological EBT 2-08 20 40 6 Processes Molecular EBT 2-03 28 56 8 Molecular & Genetic EBT 2-09 25 45 7 Biology Diagnostics Genetics EBT 2-04 18 36 5 Current Topic II (every EBT 2-010 3 7 1 semester) Microbiology EBT 2-05 27 50 8 Pharmaceutical EBT 2-011 17 33 5 and Virology Biotechnology & Drug Engineering Current Topic I EBT 2-06 4 6 1 Animal Biotechnology & EBT 2-012 17 33 5 (every semester) Tissue Engineering Plant Biotechnology EBT 2-013 17 33 5 Food Processing EBT 2-014 17 33 5 New Topic EBT 2-015 17 33 5 Bioprocess & Bioengineering Fundamentals Summer Stage 15

III YEAR

V SEMESTER VI SEMESTER

MODULES EBT 3 Hrs. Hrs. CREDITS MODULES Hrs. Hrs. CREDITS Lecture Practice Lecture Practice Quality Control EBT 3-01 17 33 5 Thesis -- -- 30 & Assurance Business & EBT 3-02 13 27 4 Project Management Patent & Law EBT 3-03 10 20 3

Bioinformatics EBT 3-04 27 53 8

Biomaterials and EBT 3-05 17 33 5 Biocompatibility Industrial EBT 3-06 13 27 4 Simulation & Case Study Current Topic I EBT 3-07 4 6 1 (every semester)

I YEAR

I SEMESTER

MODULES EBT 1 Hrs. Lecture Hrs. Practice CREDITS

General and Inorganic EBT 1-01 20 40 7 Chemistry Organic Chemistry EBT 1–02 25 50 8

Computers & EBT 1–03 15 30 5 Biostatistics Physical and EBT 1–04 25 50 7 mathematical fundamentals for biotechnology Bioethics EBT I-05 10 20 2

Current Topic EBT 1-06 5 10 1 (every semester)

EBT 1-01 GENERAL AND INORGANIC Hours: LECTURES 20 CHEMISTRY PRACTICE 40 CREDITS 7 Lectures Topics Practical Session 1. Stoichiometry and the Basis of Atomic Theory 1. Numerical tests and stoichiometric problems 2. The Electronic Structure of Atoms 2. Preparations and Dilutions of Chemical Reagents 3. The Chemical Bond and Valence 3. Acis-Base Titrations 4. Periodic Properties 4. pH Determinations 5. Chemical Equilibrium 5. Other laboratory techniques and applications 6. Ionic Equilibria in Aqueous Solution 7. Oxidation-Reduction Reactions 8. Principal Properties of Gaseous, Solid, and Liquid State 9. Elements of Chemical Thermodynamics and Kinetics 10. Elements of Bioinorganic Chemistry

EBT 1–02 ORGANIC CHEMISTRY Hours: Lectures 25 Practice 50 Credits 8 Lectures Topics Practical Session 1. Nomenclature, functions and structure of organic compounds 1. Exercises of Organic Chemistry 2. Hybrid orbitals and carbon bonds 2. Guidelines for organic laboratory practice 3. Isomeric structures and conformational analysis 3. Examples of organic syntheses 4. Elements of stereochemistry 4. Chemistry database search 5. Functional groups 6. Reaction mechanisms 7. Aromaticity

EBT 1–03 COMPUTER BIOSTATISTIC Hours: Proposed Programme Lectures 15 by Prof. Mario Comelli, University of Pavia, Italy Practice 30 Credits 5

Lectures Topics Practical Session

1. The scope of statistics in the biological sciences. The role of statistics in Lab. activities on the lecture topics. each operative phase of a biological or biotechnological research (1/0) 2. Statistical variables and levels of measurement. Frequency distributions and cross-tabulations for qualitative and quantitative variables (2/3) 3. Graphical representation of frequency distributions and cross-tabulations (histograms, pie-charts stem and leaf plots etc.) (0/2) 4. Position and variability indices (mean, quantiles, standard deviation, etc.). Association indices of two statistical variables (correlation, Spearman’s correlation) (2/1) 5. Frequency limit and Bayesian concepts of probability, axioms of probability. Probability of mutually exclusive and independent events (2/2) 6. Sensitivity, specificity and ROC curves (1/1) 7. Continuous and discrete random variables. Probability density and distribution functions. Expected value of a random variable (1/1) 8. Some probability models for discrete random variables (binomial, Poisson) (2/1) 9. Some probability models for continuous random variables (exponential, Gaussian). Tolerance limits for a Gaussian population (2/2) 10. Point estimate of the parameters of some probability model. Concept of standard error (1/0) 11. Sampling distribution of the arithmetic mean, statement of the central limit theorem (1/1) 12. Statistical test (null hypothesis, type I and II error, P-value, power optimization). The Z test. (3/3) 13. T-test for one or two independent and paired samples (1/2) 14. Confidence interval for the expected value of a random variable (2/2) 15. Asymptotic sampling distribution of an observed proportion. Chi square test, confidence interval for an unknown proportion (2/2).

EBT 1–04 PHYSICAL AND MATHEMATICAL Hours: FUNDAMENTALS FOR BIOTECHNOLOGY Lectures 25 Practice 50 Credits 7 Lectures Topics Practical Session I Part: Lab. activities on the lecture topics. 1.- Review of basic mathematical concepts. 2.- Fourier Analysis. 3.- Differential equations applied to biotechnology II Part: 1.- Physical Fundamentals. 2.- Applied Fluid Dynamics. III Part: 1.- Applied Optical Physics. IV Part: 1.- Applied Electricity and circuits theory. 2.- Applied Electromagnetism.

EBT I-05

BIOETHICS Hours: Lectures 10 Practice 20 Credits 2

Lectures Topics Practical sessions - Bioethics and the media: The influence of science journalism on popular ethic Lab. activities on the lecture topics. - Reproduction ethics: autonomy, ethics, and decision-making - The ethic of profit: the interplay of bioethics and industry - The ethics of cloning - Biotechnology, food security and the developing world - Bioethics and the biotech industry - Bioethics and the pharmaceutical industry - The foundations of Bioethics: contingency and relevance - Plant Biotechnologies: advantages and limits - Environmental biotechnologies - Introduction to bioethics in contemporary medicine - Toward a 21st century bioethic

I YEAR

II SEMESTER

MODULES EBT 1 Hrs. Lecture Hrs. Practice CREDITS Biochemistry EBT 1-07 25 45 7

Cell Biology & EBT 1-08 25 45 7 General Histology Biophysics EBT 1-09 14 26 4

Plant and Human EBT 1-010 14 26 4 Physiology

Instrumental Analysis EBT 1-011 24 46 7

Current Topic EBT 1-012 4 6 1 (every semester) Summer Stage 15

EBT 1-07

BIOCHEMISTRY Hours: Lectures 25 Practice 45 CREDITS 7

Practical Session Lectures Topics Laboratory methods: Automatic pipettes and spectrophotometry Amino acids: Colour reactions of amino acids Proteins: Separation of amino acids by thin-layer chromatography; − Amino acids and proteins. Electrophoresis of serum proteins on cellulose acetate; Precipitation of proteins

− Enzymes. by denaturation. Isolation of albumins and globulins by precipitation with − Bioenergetics, citric acid cycle as an universal amphibolic mechanism. ammonium sulphate; Quantitative determination of serum proteins; Dialysis; − METABOLISM OF SACCHARIDES. The separation of potassium hexacynoferrate(III) from ferrihemoglobin using gel chromatography. − Metabolism of lipids. Enzymes: Amylase specificity; Effect of temperature, pH and substrate concentration on enzyme activity. Michaelis constant. − Metabolism of amino acids and their metabolic derivatives. Bioenergetics: Effect of mitochondrial electron transport chain inhibitors on substrate oxidation by mitochondria isolated from rat liver. (Course used in IFB Gdansk). Lipids: Determination of triacylglycerols using acetylacetone and enzymatic methods. Saccharides: Determination of glucose in blood. Nucleic acids (basic assignment): Hydrolysis of DNA and RNA and determination of their components, Nucleic acid absorption spectrum, chromatography of ATP hydrolysate. Clinical chemistry (example): Determination of aspartate aminotransferase (ALT) and alanine transferase activities in serum

EBT 1-08 CELL BIOLOGY/HISTOLOGY Hours: Lectures 25 Practice 45 CREDITS 7 Lectures Topics Practical sessions 1 course content/organisation; 2 compartmentation of eukaryote cells; 1. Setting up the microscope. Analysis of blood smears; 3 endomembrane system: structure & function of endoplasmic reticulum; 2. Light microscopy; mitosis; root squash preparation; analysis of mitoses; 4-5 Golgi apparatus, lysosomes, peroxisomes; 3. Fluorescence microscopy; flow cytometry; fluorescence activated cell 6 nucleic acid structure; sorting; 7 nucleus, nucleolus, chromatin structure & function; 4. Scanning & transmission electron microscopy analysis of electron 8 mitosis & meiosis; micrographs; 9 cell cycle: concepts, evaluation, control; 5. Phase contrast microscopy; buccal smears, amoeba structure and movement; 10 RNA processing m-RNA, T-RNA, r-RNA; 6. Introduction to cytochemistry; tissue preparation; methods for nucleic acids, 11 protein synthesis; proteins; 12 structure and function of proteins; 7. Methods for carbohydrates and lipids; 13 structure and function of lipids; 8. Histological staining - haematoxylin and eosin: 14 membrane structure and component molecules; 9. Histology of blood/epithelia; 15 membrane transport processes; 10. Histology of kidney and liver; 16 plasma-membrane & mass transport; 11. Histology of the intestinal tract. 17 cytoskeleton; 18 mitochondria: cytosol-structure :function; 19 compartmentation; 20 introduction to histology; tissue preparation- chemistry of fixation, smears, paraffin and plastic embedding; 21 theory of tissue freezing, frozen sectioning, chemistry of staining, temporary/permanent mounts; 22 histology of blood, epithelia; 23 histology of intestine/stomach; liver; kidney;

EBT 1-09 BIOPHYSICS Hours: Lectures 14 Practice 26 CREDITS 4

Lectures Topics Practical sessions I Part: Lab. activities on the lecture topics. 1.- Introduction to living systems physics. 2.- Fluid mechanics in living systems. II Part: 1.- Transport phenomena and cellular migration. III Part: 1.- Bioelectrical phenomena in cells and tissues.

EBT 1-010 PLANT AND HUMAN PHYSIOLOGY Hours: Lectures 14 Practice 26 CREDITS 7

PLANT PHYSIOLOGY AND PLANT PHYSIOLOGY Lectures Topics Plant structure and organisation: the plant cell, the plant embryo, meristems, Practical sessions primary and secondary structure. Plants, water and solutes; active and passive transport; water movement; water 1. General anatomy of the root, shoot, leaf, vascular tissues in mono- and di- potential transpiration;.stomata. cotyledonous plants. Mineral nutrition: macro- and micronutrients; nitrogen. 2. Growth analysis, gas exchange and photosynthesis. Photosynthesis and photosynthetic end product synthesis: photosynthetic 3. Measurements of plant pigments: chlorophylls and lycopene apparatus; light reactions, carbon reactions; photorespiration; C3, C4 and CAM; starch and sucrose synthesis; synthesis of polialcols, raffinose and fructans; 4. Measurements of plant carbohydrates. phloem loading, transport and unloading; source-sink relationships. Respiratory metabolism: glycolysis; the TCA cycle; electron transport; cyanide- resistant respiration; the pentose phosphate cycle. Lipid metabolism and gluconeogenesis. Seed and germination. Plant hormones. Phytocrome. Secondary metabolism.

HUMAN PHYSIOLOGY HUMAN PHYSIOLOGY Lectures Topics 1. Structure of the central and peripheral nervous system. Methods of Practical sessions investigation. Morphology of neurons, glia and axons. 1. Structure and ultra-structure of nervous system. Study methods. Selective Circulatory system111 staining of grey matter and white matter, dissection of the nervous system in Structure and function of muscle. an amphibian (frog) and in a mammal (mouse). 2. Sensory receptors; touch, thermal, pain. Visual and acoustic receptors. 2. Neuromuscular synapse; experiments of Claude Bernard and Bernstein. The vestibular apparatus. Reflexes. Reproductive physiology. Effects of the local application of acetilcoline. 3. Membrane potential; passive ionic channels, chemical and electrical 3. Isotonic and isometric contraction, thecniques of miography. gradients, equilibrium potential for an ion, metabolic pumps; action 4. Anodic and cathodic blocks. Non-polarizable electrodes. EEG and EMG. potential. 4. 4. Relation of diameter and conduction velocity, role of myelin. Structure and function of muscle. Textbook: Taiz, L. and Zeiger, E. (1998) Plant Physiology, Second Edition. Sinauer Associates. Sunderland, MA (The third edition is due by the end of 2002.) Suggested reading : Lack A. J and Evans D. E. (2001) Instant notes in plant biology. BIOS Scientific Publishers Limited Oxford (UK)

EBT 1-011 INSTRUMENTAL ANALYSIS Hours: Lectures 14 Practice 28 CREDITS 4

Lectures Topics Practical sessions 1. Introduction to the instrumental analytical methods. The basic laboratory Atomic absorption spectroscopy; Colorimetric analysis of aqueous solutions; instrumentation for chemical analysis. Accuracy, precision, detection limits and selectivity of analytical data. Interpretation of Infrared spectra of simple molecules; Interpretation of the 2. Optical spectroscopy: general principles, typical instrumentation, light sources and NMR spectra of some common and simple molecules. Gas-chromatographic detectors. Principles of atomic spectra. Atomic absorption spectroscopy. Atomic emission spectroscopy. and mass-spectrometric analysis of a mixture of organic compounds 3. Molecular spectroscopy: light emission and absorption by molecules. The molecular dynamics. Absorption molecular spectroscopy: ultra-violet, visible and infrared. 4. Introduction to the chromatographic separation methods. General principles. Gas- Liquid and Gas-Solid Chromatography. Characteristics of typical instruments in gas chromatography. The possibilities provided by the HPLC. 5. General introduction to the Mass-Spectrometry. Different types of mass- spectrometers. The coupling of mass-spectrometry with gas chromatography. 6. Nuclear Magnetic Resonance: principles.

II YEAR

III SEMESTER

MODULES EBT 2 Hrs. Lecture Hrs. Practice CREDITS Immunology EBT 2-01 18 36 5

Cell Culture EBT 2-02 7 14 3

Molecular Biology EBT 2-03 28 56 8

Genetics EBT 2-04 18 36 5

Microbiology and EBT 2-05 27 50 8 Virology

Current Topic EBT 2-06 4 6 1 (every semester)

EBT 2-01 IMMUNOLOGY Hours: Lectures 18 Practice 36 CREDITS 5 Lectures Topics Practical sessions 1. Basic concepts in immunology How to study antigens by antibodies: 2. Cells of the immune system Immunodiffusion, Radial Immunodiffusion (Mancini) 3. The thimus and development of T lymphocytes Immunoelectrophoresis 4. The development of B cells How to measure specific antibodies: 5. Antibodies and Generation of immunoglobulin diversity Neutralisation assay 6. T cell receptor and generation of TCR diversity Enzyme linked immunosorbent assay (ELISA) 7. Induction of immune response: Antigen presenting cells Immunofluorescence 8. T cell mediated immunity: Regulatory and Cytotoxic T cells Flow cytometry 9. Humoral immune response How to study lymphocytes: 10. Innate immunity including complement and NK cells CD antigens 11. Cytokines and Chemokines in immunity Flow cytometry 12. Failures of host defence mechanisms; Vaccination, Immune sera Cell mediated immunity: Mitogen stimulation of limphocytes 13. Allergy, Autoimmunity and Cancer 14. Immunilogy in Biotechnology: monnoclonal antibodies, modern serological methods

EBT 2-02

CELL CULTURE Hours: Lectures 7 Practice 14 CREDITS 3 Lectures Topics Practical sessions 1. Sterile technique; types of media for plant and animal tissue culture. 5h each for plant and animal cultures, but not in a totally fixed way due to the 2. Preparation of animal material for tissue culture: explants; establishing cell time taken for the plant material to grow. lines. Identificaton of cell types in culture. 1. Media preparation and sterilization for plant tissue culture. Liquid and 3. Preparation of plant material for tissue culture: explants for plant solid media. Pouring of plates. regeneration, callus and somatic exmbryos; cell suspension cultures. 2. Explanting for the production of callus, organogenesis and somatic embryos. Protoplasts. Bioreactors. 3. Haploid plants from pollen. 4. Development of a mammalian cell line. 5. Culturing of a given mammalian cell line and effects of mitotic inhibitors. 6. Identification of mammalian cell types in vitro by immuno- cytochemistry.

EBT 2-03 MOLECULAR BIOLOGY Hours: Lectures 28 Practice 56 CREDITS 8

Lectures Topics Practical sessions

Organization of the eukaryotic and prokaryotic genome. Gene expression and 1. Dna purification, regulation. From gene to protein. Restriction enzymes- Modifying enzymes (DNA 2. Cloning in plasmid vector, Polymerases, RNA polymerases, Nucleases, Kinases, Phosphatases, Ligases)- 3. Dna sequencing, Cloning in plasmid vector (Preparation of the DNA fragment, Preparing the vector 4. Dna labeling, for cloning, ligation of plasmid vector and insert DNA, transformation of DNA into 5. Library screening, bacteria, analysis of trasformants, cloning PCR fragments)- Cloning in 6. Protein expression, bacteriophage lamda (preparation of genomic DNA for cloning, preparation of 7. Protein translation in vitro, lamda vectors arms for cloning, ligation of inserts to vector arms, packaging of 8. Rna purification and analysis, ligated DNA and titration of recombinant phage, screening lamda libreries, phage 9. Pcr, lysate preparation, isolation of recombinant lamda DNA)- DNA purification- RNA 10. Rt-pcr, purification and analysis (Isolation of total RNA, Isolation of mRNA, analysis of 11. Promoter assay, RNA by Nortrhern blotting, analysis of RNA by in situ hybridization)- 12. Two hybrid system, Transcription in vitro- radioactive labeling of DNA (DNA 5’-end labeling, DNA 3’- 13. Mutagenesis, end labeling, Nick traslation system, random prime labeling, deteremination of percent incorporation and specific activity)- Non-Radiactive DNA labeling (Characterization of Fluorescein- and Biotin-labeled oligonucleotides, considerations for chemioluminescent detection)- DNA sequencing- Mutagenesis (nested deletion, Site direct mutagenesis)- cDNA synthesis (Procedures for cDNA synthesis, incorporation assays, gel analysis, construction and screening of cDNA libreries)- Nucleic acid amplification (Considerations for PCR optimization, RT- PCR)- reporter gene assay (Preparation of cell extracts, Luciferase reporter gene system, CAT reporter gene system, β-galactosidase reporter gene system)- Transfection- Protein expression (prokaryotic expression vectors, Expression of Biotinylated fusion proteins, mammalian expression vectors)- Protein translation in vitro (Eukaryotic in vitro translation systems, Rabbit reticulocyte lysate, nuclease- treated, prokaryotic in vitro translation systems)- Protein analysis- Eukaryotic transcription regulation (In vitro transcription assay, primer extension analysis- RNA splicing, gel shift assay, Footprinting assay)- cellular regulation Cellular proliferation assay, cytotoxicity assay, apoptosis)- signal transduction Protein kinases, protein phosphatases )- Two hybrid system- DNA chip technology.

EBT 2-04 GENETICS Hours: Lectures 18 Practice 36 CREDITS 5 Lectures Topics Practical sessions 1. History, mendelian traits, modes of inheritance of monogenic traits. Mendelian inheritance, pedigree analysis. Analysis of linkage, molecular 2. Genes and genetic variation, polygenic and multifactorial inheritance. markers. FISH (Fluorescence in situ hybridisation. Diagnosis of mutations. 3. Genes and signalling, developmental genetics. Determination of sex. Restriction enzyme use for RFLP and the locus specific tests. In vitro and in 4. Mitochondrial and X-linked inheritance, X chromosome inactivation. vivo (virtual demonstration) tests of mutagenicity. Mutations and the cancer- 5. Mutations: somatic vs germinal. prone genotypes. In vitro and in vivo tests for protein signalling. Genetic studies 6. Mutagenesis, DNA repair and transposable elements. of cell and protein interactions 7. Gene mapping and cloning, complete genome analysis. 8. Molecular approaches to diagnosis of mutation. 9. Chromosomes and chromosomal abnormalities. 10. Gene expression and transgenes. 11. Genetic transformation in plants. 12. Populations genetics.

EBT 2-05 MICROBIOLOGY AND VIROLOGY Hours: Lectures 27 Practice 50 Credits 8 Lectures Topics Practical sessions 1. Introduction to microbiology. Cell theory. 1. Methods of sterilization. 2. Functional anatomy of bacterial cell. 2. Media for bacteria propagation. 3. Dynamics of bacteria population growth. 3. Morphological forms of bacteria. 4. Metabolism: the generation of energy and synthesis of macromolecules. 4. Bacterial physiology, type of respiration. 5. Bacterial genetics. Parasexual processes in bacterial cell. 5. Bacterial physiology, biochemical identification. 6. Interaction between humans and microorganisms, with special attention to 6. Bacteriophages. the pathogens. 7. Soil microbiology. 7. Plant pathogenic bacteria. 8. Water microbiology. 8. Microbial ecology and terrestrial microbiology. 9. Plant pathogenic bacteria– isolation and identification of bacteria from infect 9. Microbiology of aquatic environment. plant tissue. 10. Microbiology of waste treatment. 10. Human organism as a source of bacteria. 11. Microbiology of food and beverages. 11. Antibiotics, mechanisms of resistance and dissemination. 12. The nature of virus; bacterial, animal and plant viruses. 12. Influence of physical-chemical condition on bacteria propagation. 13. Classification and taxonomy of bacteria. 14. Detection, identification and differentiation of bacteria and virus using biochemical, immunological and molecular methods. 15. Microbiology and biotechnology. The basic features of genetic engineering. Application of genetic engineering; expression of cloned genes. 16. Antibiotics and their mechanisms of action. Mechanisms of antibiotics resistance. Plasmid and transposons and their role in the dissemination of antibiotics resistance. 17. Transformational spread of antibiotics resistance. Source of resistance markers in nature and their selectability for biotechnical purposes.

II YEAR

IV SEMESTER

MODULES EBT 2 Hrs. Lecture Hrs. Practice CREDITS Pharmacology & EBT 2-07 20 40 6 Toxicology Biotechnological EBT 2-08 20 40 6 Processes Molecular & Genetic EBT 2-09 25 45 7 Diagnostics Current Topic (every EBT 2-010 3 7 1 semester) Pharmaceutical EBT 2-011 17 33 5 Biotechnology & Drug Engineering- optional Animal Biotechnology EBT 2-012 17 33 5 & Tissue Engineering- optional Plant Biotechnology - EBT 2-013 17 33 5 optional Food Processing – EBT 2-014 17 33 5 optional Bioprocess and EBT 2-015 17 33 5 Bioengineering Fundamentals– optional Summer Stage 15

EBT 2-07 PHARMACOLOGY & TOXICOLOGY Hours: Lectures 20 Practice 40 Credits 6 Lectures Topics Practical sessions

General principles of pharmacology: Binding assay: Kd evaluation, High and low affinity receptors. Brief outline of pharmacokinetics Receptor signal transduction: Protein phosphorylation, Nuclear translocation. Drug adsorption, distribution, metabolism, and excretion Drug effects: Cell proliferation, Cytokine production, Apoptosis. Basic concepts in pharmacodynamics Gene transfer: Production of soluble factors by transfected cells. Drug receptors Dose-response curves: efficacy and potency Agonists and antagonists Mechanisms of drug antagonism Biochemical characterization of receptors Ligand binding and drug affinity Biochemical mechanisms and signaling Biotechnological drugs: Antisense oligonucleotides Ribozymes Decoys Gene therapy General principles of toxicology: Parameters of acute and chronic toxicology Mutagenesis and carcinogenesis Teratogenesis Allergic and idiosyncratic reactions

EBT 2-08

BIOTECHNOLOGICAL PROCESSES Hours: Lectures 20 Practice 40 Credits 6 Lectures Topics Practical sessions 1. Identification, handling and preservation of microorganism. 1. Laboratory methods for the testing the potency of diphtheria (D), tetanus (T), 2. Microbial growth and metabolism (including choice and preparation of pertussis (P) and combined vaccines. growth media). 2. The Elisa, as serological assay for the determination of antibody 3. Types of bioreactors (including stirred tank, draught tube and bubble response following vaccine immunization. column reactor). 3. Serum bactericidal assay (SBAs) for the evaluation of immune responses to 4. The industrial fermentation process. serogroup A/c meningococcal vaccines. 5. Downstream-processing. 4. Animal models for studying the immunogenicity of vaccine preparations. 6. Overproduction and manipulation on the primary metabolism. 7. Biotrasformations/Bioconversions (including immobilization strategies). 8. Production techniques for antibiotics and other secondary metabolites. 9. Production of biopolymers (including bioplastics). 10. Enzymes-isolation. Stability and stabilization/renaturation. 11. Enzymes-immobilization and coupling technology (biosensors). 12. Application of recombinant DNA technology (recomnbinant expression of proteins). 13. Bioremediation of water and air (environmental biotechnology part 1). 14. Bioremediation of soil (environmental biotechnology part 2): 15. Sustainable production of fuels (petrol and diesel replacements). 16. Alternative fuels (biologically produced hydrogen). 17. Oil and mineral recovery. 18. Single cell protein (including open pond algal systems). 19. Microbes in agriculture (frost protection and pesticides). 20. Production of vaccines).

EBT 2-09 GENETIC AND MOLECULAR DIAGNOSTICS Hours: Lectures 25 Practice 45 Credits 7

Lectures Topics Practical sessions Classification of mutations Storage and handling of genetic material. Isolation of DNA and RNA. Physical Translocations and chemical characterisation of DNA. Amplification of DNA by PCR. Detection of mutations and Translocations Sequencing of DNA. Restriction analysis and hybridisation with molecular Amplification of DNA by PCR probes. Detection of mutation by RFLP, SSCP, HD and PTT analyses. DNA Sequencing of DNA fingerprinting. Analysis of short tandem repeats. Analysis of DNA Molecular diagnostics of viral infection polymorphism. Molecular diagnostics of bacterial infection Preparation and staining of mitolic metaphase chromosomes. Numeric and Detection of parasites structural anomalies of autosomes and sex chromosomes. FISH. Analysis of Molecular diagnostics of genetic diseases: human cytogenetics, trisomies and translocations. monosomies Structural anomalies of autosomes and sex chromosomes Molecular diagnostics of cancer diseases: chromosomal instability in cancer Constant chromosomal aberrations in neoplasia Translocations and cancer Site directed mutagenesis Analysis of DNA using microchips

EBT 2-011 PHARMACEUTICAL BIOTECHNOLOGY – Hours: DRUG ENGINEERING Lectures 17 Practice 33 Credits 5 Lectures Topics Practical sessions

1. General Principles of Medicinal Chemistry: Computer-assisted drug design: Specific and Nonspecific Drugs. Pharmacokinetics and pharmacodynamics. Searching of databases. Drug Receptor Interactions. Rational Bases for Drug Design. Molecular Retrivial and analysis of proteins and DNAs. Modeling in Drug Design. Construction of protein models. 2. Structure and Analysis of Proteins: Simulation of peptides-proteins interactions. Primary, Secondary and Tertiary Structure. Folding of proteins. Methods for Methods of quantitative structure activity relationships. folding prediction. Analytical techniques of proteins Analytical Chemistry 3. Pharmacodynamics of Peptidic Drugs: Peptides as potential drugs. Peptidic drug-receptor interactions. Binding of Electrophoresis: peptidic drugs to proteins. HPLC 4. pBiotechnological Technologies: GC Genetically modified animals and their relevance in drug discovery. Genetically modified proteins. Petidomimetics. Oligonucleotides. Combinatorial chemistry Biotechnological Drugs Costs and timing for the discovery of drugs. Impact and relevance of biotechnological approaches to drug discovery. Analysis of selected classes of peptidic, proteic and oligonucleotidic drugs currently in the market or in development.

EBT 2-012 ANIMAL BIOTECHNOLOGY Hours: AND TISSUE ENGINEERING Lectures 17 Practice 33 Credits 5 Lectures Topics Practical sessions Animal Biotechnology: the transgene technology Lab. activities on the above arguments. I. Transgenic Animals – 1 credit 1. Transgenic Animal: definition 2. Steps in producing a transgenic animal. A. Superovulation of Donor animal, B. Fertilization (in vivo or in vitro) and Collection of oocytes or embryos, C. Insertion of Recombinant DNA into Embryo, D. In Vitro Maturation of embryo, E. Embryo Transfer to Recipient animals, F. Gestation and Parturtion, G. DNA from offspring analyzed for presence of transgene. 3. Methods of getting Recombinant DNA into the embryo A. Microinjection of recombinant DNA into pronuclei (male) of 1 cell embryo or zygote, before syngamy occurs, B. Retroviral Vectors, C. Embryonic Stem (ES) Cells, D. Sperm has also been proposed as a vector 4. New Method of Producing Transgenics A. Nuclear Transfer/Cloning, B. Gene Targeting, C. Spermatogonal Transfer 5. Technical problems with producing transgenic livestock A. Very low efficiency <1%, B. Opaque Ova, C. Long Generation Time, D. Most farm species can only carry two zygotes to term, E. FDA approval???? II. Applications of Transgenic Animals 1. Transgenic Mice A. Valuable Research Tool--Basic Research, B. Model for Diseases 2. Transgenic Livestock A. Improved Production Traits a. Somatotropin/Growth Hormone, b. Stimulation of muscle development: c- SKI gene, c. Wool Production: Improve Cysteine Utilization B. Improve Animal Health a. Incorporate disease resistance genes, b. Preformed antibodies, c. Interferon

C. Transgenic Milk a. Why Milk?, b. Dairy Pharming: Production of medically important products in milk. --Factor IX(Hemophilia) --Protein C (Thrombosis) --Hemoglobin (Artificial Blood) --Tissue Plasiminogen Activator (Heart Attacks) --Human Alpha-1-Antitrypsin (Emphysema) --Peptide Hormones and Growth Factors c. Manipulation of components already in milk D. Human a. Incorporate human genes into pig organs for transplants – can it work? 3. Transgenic Birds & Eggs A. Eggs have advantages similar to milk a. Ovalbumin, b. Production of antibodies B. Blastoderm transfection a. Blastoderm cells transfected by lipofection--cationic lipid/transgene complex (liposome), b. Recipient Blastoderm cells irradiated, c. Donor Blastoderms injected into subgerminal space. 4. Transgenic Fish A. Efficient microinjection: a. Cytoplasmic injection, b. Microinjection survival, c. Production of transgenics B. Embryo Development in external environment 5. Transgenic Amphibians and Reptiles A. Valuable Research Tool--Basic Research III. Gene Therapy 1. Genetic Treatment of (Human) Disease A. Somatic cells and germ cells a. Ethics, b. Safety, c. Technical Problems B. Single gene disorders targeted C. Human Studies Preclinical, b. Phase I trials, c. Phase II trials, d. Phase III trials 2. Ex vivo therapy A. Steps: a. Collect cells from affected individual, b. Correct gene defect by gene transfer, c. Select and grow genetically corrected Cells, d. Infuse or transplant cells back into patient B. Bone Marrow diseases most likely candidates a. Bone Marrow contains stem cells C. Universal Donor cells 3. In vivo therapy A. Direct Delivery, B. Tissue Specific Promoter on expressible remedial gene, C. Viral Infection

organ transplant4. Antisense therapy A. Uses antisense DNA to block or lower translation of detrimental mRNAs B. Strategies a. Antisense oligonucleotides--DNA:RNA hybrid, b. Antisense gene--RNA:RNA hybrid Tissue Engineering I. Cell culture scale-up 1. Bioreactors A. Suspension cultures of monodispersed cells, B. Adherent cultures, C. Suspension cultures of aggregated cells II. Extracellular Matrix 1. Structure and Function, 2. Cell Adhesion, Adhesive Receptors and Ligands, 3. Cell Migration III. Biological Matrices for Tissue Regeneration 1. Importance of Mechanical Environment for Tissue Engineering 2. Synthetic Biodegradable Polymer Scaffolds. A. Skin, B. Cartilage, C. Blood Vessels, D. Collagen Scaffolds for Vascular Conducts 3. Small Intestinal Submucosa: A Bioscaffold for Tissue Repair IV. Strategies for Repair 1. Articular Cartilage, 2. Skin and epithelia, 3. Biohybrid Artificial Pancreas, 4. Hybrid Artificial Liver, 5. Bone Formation, Repair, and Regeneration, 6. Adipose Tissue Engineering, 7.Blood Substitutes, 8. Muscle: skeletal and cardiac, 9. Strategies for Vascularization of Tissue Engineered Implants, 10. Regulation of Blood Vessel Formation, 11. Tissue Engineered Cardiovascular Implants, 12. The Use of Stem cells V. Application of Robotics 1. Principles of Drug Discovery and Tissue Engineering, 2. Drug Delivery for Tissue Engineering, 3. Protein Delivery Systems for Regeneration of Bone and Cartilage

EBT 2-013 PLANT BIOTECHNOLOGY Hours:

Lectures 17 Practice 33 Credits 5

Lectures Topics Practical sessions 1. An introduction to plant biotechnology-the potential for exploitation of plants; discussion of the scope of Isolation of plant material and studies on growth plant biotechnology, its possibilities, advantages and disadvantages; central role of plant tissue culture in and cell division in vitro. Advanced plant tissue plant biotechnology; range of in vitro techniques available (cell, tissue, organ and protoplast cultures). culture techniques: morphogenesis, suspensions & 2. Plant tissue culture in practice-basic methodologies for the initiation and maintenance of callus, micropropagation suspension and tissue cultures, and for the production of protoplasts. Transformation with A. rhizogenes. Production of 3. Plant bio-regulators: auxins, cytokinins, gibberellins, abscisic acid, ethylene, jasmonic acid, polyamines monoterpenes in plant tissue cultures. 4. Genetic transformation of plants-Consideration of Agrobacterium mediated transformation and direct genetic transformation (comprising the biolistic method, the SiC whisker method, laser-mediated transformation, electroporation, micro-injection and protoplast techniques); advantages and disadvantages. 5. Genetic transformation of plants: construction of chimeric genes (promoters, terminators, marker genes, reporter genes, selectable genes). 6. Regeneration and micro-propagation: organogenesis and embryogenesis; induction of differentiation; conditions for morphogenesis; competence for regeneration; somatic embryo-genesis; theory and practice of micro-propagation. 7. Herbicide resistance in plants: general strategies for increasing herbicide resistance through the genetic modification of plants; case studies e.g. glyphosate, phosphinothrycin, bromoxynil and 2,4-D. 8. Strategies of metabolic engineering; sense and anti-sense insertions; example of genetically modified medicinal plants in which secondary compound yield has been modified; seed transformation. 9. Disease resistance in plants-meristem tip propagation for virus free plants; production of somaclonal variants from protoplast and tissue culture with enhanced disease resistance; mechanism and genetics of disease resistance at the molecular level; distinction between resistance genes (R-genes) and disease response genes (Hypersensitive Response genes); examples of genetic engineered crop plants with enhanced disease resistance. 10. Phytoremediation-the use of plants and plant cultures for the removal of organic and metal contaminants; plants which hyper-accumulate metals and their use in phytoextraction; phytoextraction in aqueous environments (plants and sea-weeds); rhizofiltration; phytodegradation; phytostabilisation; perspectives using genetically modified plants.

EBT 2-014 FOOD PROCESSING AND Hours: MICROORGANISMS Lectures 17 Practice 33 Credits 5

Lectures Topics Practical sessions Aim of the course: the course deals with the main implications of micro- 1. Sampling methods in foods organisms in plant and animal food processing in order to achieve some 2. Methods for determining food micro-organisms: knowledge about the theory and practice for controlling the use of microbial biological, chemical, physical, molecular, immunological starters and for preventing microbial spoilage and food poisoning. 3. Detection of indicators of food microbial quality and safety 1. Synopsis of common food micro-organisms 4. The HACCP system and food safety: 2. Intrinsic and extrinsic parameters of foods and beverages that affect application to dairy products microbial growth application to meat products 3. Food preservation with chemicals, radiation and drying application to fruit and vegetable products 4. Low-temperature food preservation and HTST processing 5. Methods for selecting food starter cultures: 5. Fermented milk processing isolation and identification of food endogenous micro-organisms 6. Cheese processing enzyme characterisation 7. Baked goods processing characterisation for antimicrobial activity 8. Processed meats and poultry scale up of the selected starter cultures 9. Fresh and fermented fruit and vegetables 6. Enzymes selection for foods 7. Production of physiologically active compounds for functional foods

EBT 2-015 BIOPROCESS AND BIOENGINEERING Hours: FUNDAMENTALS Lectures 17 New Topic Practice 33 Credits 5 proposed by Proff. R. Pohorecki and K. W. Szewczyk, Warsaw University of Technology, Poland Lectures Topics Practical sessions A. Thermodynamics and kinetics of biotechnological processes 1. Analysis of biomass 1. Mass and energy balances 2. Kinetics of sterilization 2. Kinetics of enzymatic reactions 3. Mass transfer during aeration 3. Kinetics of microbial growth and metabolite production 4. Batch reactor with submerged culture B. BIOREACTOR ENGINEERING 5. Fed-batch culture 4. Bioreactor design and configuration 6. Reactor with immobilized cells 5. Bioreactor hydrodynamics 7. Membrane reactor 6. Transport phenomena in bioreactors 8. Enzyme precipitation and purification 7. Dynamics and control of bioreactors 9. Wastewater treatment in SBR reactor 8. Scaling – up of bioreactors C. Up- and downstream processing] 9. Substrate preparation and sterilization 10. Product recovery operations 11. Cell harvesting 12. Separation and purification of products 13. Product recovery plants 14. Elements of process economics

Suggested textbooks 1. Roels J.A. “Energetic and Kinetics in Biotechnology” (1983), Elsevier Biomedical Press, Amsterdam 2. Bailey J.E., Ollis D.F. “Biochemical Engineering Fundamentals” (1986) Mc Graw-Hill, New York 3. Rehm H-.J., Reed G. “Biotechnology” vol 3 (1983), Verlag Chemie, Weinheim

Prerequisites: EBT 1-01 General and inorganic chemistry EBT 1-04 Physical and mathematical fundamentals for biotechnolog

III YEAR

V SEMESTER

MODULES EBT 3 Hrs. Lecture Hrs. Practice CREDITS Quality Control & EBT 3-01 17 33 5 Assurance Business & Project EBT 3-02 13 27 4 Management Patent & Law EBT 3-03 10 20 3

Bioinformatics EBT 3-04 27 53 8

Biomaterials and EBT 3-05 17 33 5 Biocompatibility Industrial Simulation EBT 3-06 13 27 4 & Case Study Current Topic EBT 3-07 4 6 1

EBT 3-01 QUALITY CONTROL AND Hours: ASSURANCE Lectures 17 Practice 33 Credits 5 Lectures Topics Practical sessions Basic concepts in quality assessment How to measure tissue criteria pH, conductivity, shear values, color, others in different materials Accuracy, precision, reproducibility, Dimensions How to analyze moisture, dry matter, protein, lipids, crude fiber, vitamins, Measurements and methods minerals in different materials Physical – mechanical, Weights, Density, Resistance, Reflection and How to measure specific quality criteria by NIR and FTIR for quality control transmission, NIR, FTIR, and on-line production technology Chemical How to study time – temperature relationships in shelf life of different materials Standard methods How to calculate precision, accuracy and repeatability in different criteria form Dry matter, moisture, Protein, fat, minerals, crude fiber, vitamins, practical measurements. Advanced Methods Gaschromatography High Performance liquid chromatography Detectors, Sensor technologies Sensoric Scaling of sensoric criteria, Triangle testing Genetic Detection of genetically modified organisms, Testing for mutations (MHS-gen, rn-gen), Testing for identity Quality of products of animal origin Meat (beef, pork, poultry, others), Muscle, fat, connective tissue, bone, Meat quality analysis and measurements, Milk (fat, protein, vitamins, technological and other aspects), Eggs (fat, protein, technological and other aspects). Quality of products of plant origin Cereals, Oilseeds, Vegetables, Fruits, Others. HACCP – concept 2

EBT 3-02 BUSINESS AND PROJECT Hours: MANAGEMENT Lectures 13 Practice 27 Credits 4 Lectures Topics Practical sessions Introduction to business management (BM). EM and PM basic glossary presentation. Basic principles and methods to develop and run a business Application of computer assisted programs to set up business and marketing Managing of internal and external factors influencing the business. plans and to use friendly PM tools and techniques. Business plan, Marketing research, plan preparation and evaluation techniques. Financial and Human Resource management. Basic accounting procedures. Introduction to Project Management (PM) Project life cycle Initiation. Definition/Planning/Scheduling. Implementation. Close - down. Project scope, time, cost, quality, procurement, risk and resources management. PM tools and techniques Work Breakdown structure (WBS). Gantt Chart. Program Evaluation Review Techniques (PERT) / Critical Path Method (CPM) diagrams. Project monitoring and control Meetings (kick-off, check and final meetings. Brain storm) and Project status reporting procedures. Unforeseen event and contingencies handling methods. Corrective actions.

EBT 3-03

PATENT AND LAW Hours: Lectures 10 Practice 20 Credits 3

Lectures Topics Practical sessions Introduction to Intellectual property (IP) IP glossary presentation Definitions. Inventions and discoveries. IP identification process. Legal forms Individual practicals in on-line search of patents in data banks and preparation of IP exploiting and prior disclosing. IP protection benefits. of the prior art report of two inventions (a product and a technology). IP development and maintenance Refresher seminars held by experts on biotechnological IP rights and Invention patentability requirements. Inventorship and ownership, regulations. determination criteria. Patent data bases. Patent application types, users, executors and agents. Invention specification (title, technical field, state of the art, detailed description, experimental plans, examples, claims) and Examiners. Patent rights. National and foreign patent filling and maintenance costs. Biotechnological invention patenting

EBT 3-04 BIOINFORMATICS Hours: Proposed by Prof. Jan Paèes, Charles University Prague Lectures 27 Practice 53 Credits 8

Lectures Topics Practical sessions Keywords: Lab. activities on the above arguments. biological databases; nucleotide sequence analysis; protein sequence analysis; alignment; multiple alignment; secondary structure prediction; molecular modeling Prerequisites: good knowledge of molecular biology and genetics; working with PC (internet, text editor ..); basic principles of programming Syllabus: Introduction: • Overview • What is Bioinformatics? • What information is hidden in DNA and amino acids sequences? • www resources Databases: • Basic principles • SQL (Structured Query Language) • Molecular biological databases • Gen Bank, EMBL, SWISSPROT, Entrez, PDB Alignment: • Principles • Pattern search, dot-plot analysis • Smith-Watermann and Needleman-Wunsch algorithms • Ssearch, FastA, BLAST • Advanced methods • Neural networks and Hidden Markov Models • Psi-BLAST, Phi-BLAST, HMMER Multiple • Principles alignment: • ClustalW, Dialign, Multalign

Phylogenetics: • Principles • Evolution trees • Algorithmic and optimization methods • UGPMA, WGPMA, Neighbor joining, Parsimony, Maximum Likelihood Gene predictions: • Principles • Eukaryotics vs. prokaryotics predictions Protein analysis • Domain structure. • Secondary structure prediction • Protein folding, 3D modeling Structure alignment

EBT 3-05 BIOMATERIALS Hours: BIOCOMPATIBILITY Lectures 17 Practice 33 Credits 5 Lectures Topics Practical sessions

The course addresses mainly the integration of the knowledge on materials and 1. Structural characterisation of materials: metallography, X-ray, UV-VIS- tissue properties. Course topics include the concept of Biocompatibility and the NIR spectroscopy; reaction of the human body to implants; science and technology of materials used for implants (metals, ceramics, polymers) and examples of applications for 2. Thermal characterisation of materials: calorimetry (DSC), prosthesis production. Then, the first part will be mainly devoted to the thermogravimetry (TGA), thermo mechanical analysis (TMA); physicochemical properties of human tissues and the relationship between 3. Mechanical characterisation of materials: stress-strain curves, fracture structure and properties and their interaction with prosthetic materials. The mechanics, adhesion, fatigue, creep. second part will be devoted specifically to prosthetic materials, their properties and Biocompatibility. Finally, the third part will be devoted to the technological 4. Deposition techniques of inorganic films: plasma enhanced chemical and functional analysis of specific prosthetic systems. vapour deposition (PEVCD). Human tissues, Propriety and functions. Soft and hard tissues. Fluids (blood, 5. Deposition techniques of bio-organic compounds: Langmuir-Blodgett films etc.), Relationship structure-property in human tissues of proteins Morphology, mechanical properties, rheological properties, transport properties, biomechanics. 6. Deposition techniques of bio-organic compounds: self-assembling Biocompatibility monolayers and surface chemical derivatisation Definitions, interaction tissue-materials. 7. Thin films characterisation: Spectroscopic methods, mechanical Materials, Structure, properties, technology of materials. Metals, ceramics, characterization polymers and composite materials. 8. Experiments of cell and enzymes attachment and immobilisation in Prosthesis, Proprieties, biofunctionality and technological processes. polymer matrix. Orthopaedic and vascular prosthesis. Artificial heart. Dental prosthesis, maxillo-facial prosthesis, prosthesis in ophthalmology. (Other applications: 9. Biosensors surgery, controlled drug release) 10. Active membranes and their use in dialysis: blood-polymer interactions 11. Protein and DNA microarray and their use in biomedical research.

EBT 3-06 INDUSTRIAL SIMULATION & CASE Hours: STUDY LECTURES 13 Practice 27 Credits 4 Lectures Topics Practical sessions Biotechnological inventions transfer process from Universities to industrial Computer based business simulation exercises of grouped students: facilities. to gain experience to link R. & D. and market and sale activities working in Approaches to exploitation of inventions and IP protection. Preliminary cross-functional teams. technical and marketing feasibility assessments. Market and business planning. to investigate the opportunities for industrial and commercial exploitation of Risk evaluation analysis. Product/technology development. Licensing to spin- research ideas through the building of scientific and business plans to attract off/start-up or established companies. Financing and economical revenues. real interest of potential investors in the creation of knowledge based venture. Introduction to theory and methodology of industrial simulations and case to make basic decision in product development, in marketing and financial studies. activity and in resource utilisation. Case studies to identify, evaluate and manage the risk. Exploration of case histories of development of biotechnology based spin-off and/or start companies operating in the field of Health Care (Therapeutics and Diagnostics).

III YEAR

VI SEMESTER

MODULES Hrs. Lecture Hrs. Practice CREDITS Thesis -- -- 30

Attachment 1 Current topics

AIM OF THESE SEMINARS IS ENABLING STUDENTS TO LEARN BY MEANS OF EPOCHAL THEORIES (E.G. THEORY OF RELATIVITY), ANALYSE HABITS OF THINKING, CROSS BORDERS AND FORM CRITICALLY NEW JUDGEMENTS. MAXIMAL TIME: 24 HOURS AT 45 MINUTES.

Modules: - New society (profiles of demand under technological, philosophical and sociological perspectives: education as necessity and human right, information as value of its own etc. - Gödels 2nd theorem (stimulus of mathematics for innovative thinking: border crossings) - Poincaré’s rule of innovation („Pour inventer il faut penser à coté“ – not thinking sometimes leads to the aim) - Butlers method of reverse („A chicken is the method of an egg, to produce a new egg). - Implications of truth (two times „untrue“ may become „true“– curiosities of formal reasoning) - Modification of time in the relativistic cone of light (what we see is always the past) - Curvature of space-time (how gravitation produce a difference between the perceived position of a star and its real position). - Relativity of movement (movement and rest, a matter of position) - Relativity of time (two hours are not everywhere two hours – why the flying time of myons is longer than their lifetime) - Einstein´s ride on a beam of light (our reach into physical space zero) - 1st law of thermodynamics (an unusual application: the energy of our body is as old as the world) - 2nd law of thermodynamics (asymmetry of time: outrider for redefining logic of nature’s laws ) - Cosmological Big Bang (how and why the initial singularity (radius < 10-14 m) contained all energy of todays world) - Electromagnetic Spectrum (window to the world) - Effect of Doppler/changes of red light spectra (light not only illuminates, it also informs) - Proportions between atomic nucleus and atomic shell („Solid matter is as empty as space”) - Double opening experiment (The dualism of wave and particle – a problem of traditional logic?) - Heisenbergs relation („We don’t recognize the nature, but only our relation to it“) - Non human animals rational - Kaniza-triangle (brain does’n reproduce the world, but produces it – neurobiological constructivism) - Neglect-Patients (eye intact and nevertheless blind: loss of one half of the world) - Limbic System („I feel therefore I am“. The dichotomy of thinking and feeling – an ideological construct of the past) - The neuron (only two conditions – from the variety of the outside world to the simplicity of the brain) - Neuronal network (coherency: from topological wide spread representations to the unity of the phenomens) - SHRDLU (early surprises by AI (artificial intelligence)-dialog machines: meta-language and changes of view-points) - CPU (information or flow of electrons?) - ASCII-Code (reduction of the world to zeroes and ones – equivalency to the neuronal language of brain?)

Attachment 2 Current topics MOLECULAR EPIDEMIOLOGY

- Conceptual framework of Molecular Epidemiology.

- The basic concepts and techniques of molecular Biology in Epidemiology.

- The validations of biomarkers.

- The biological monitoring in the esposition assessment.

- The epidemiological design in molecular epidemiology.

- Statistical methods in molecular epidemiology.

- Biological speciesand bank as a resource in molecular epidemiology studies.

- The use of biomarkers in the risk assessment.

- Practical applications in chronic and infectious diseases.

- The biomarkers in the study of environmental liver diseases.

TEXTBOOKS SUGGESTED by Prof. Uldis Viesturs: C.Ratledge, B.Kristiansen "Basic Biotechnology", Cambridge University Press, 2001. W.Brains "Biotechnology from A to Z", Oxford University Press, 2000. (The definition of Biotechnology on pp. 66-67). Classical 12 Vol. "Biotechnology", H-J.Rehm, G.Reed (Eds.) (especially Vol. 3 "Bioprocessing" and Vol. 11 "Environmental Processes"). by Prof. Josè Kenny: J. B. Park, Biomaterials-an lntroduction, Plenum Press Y. C. Fung, Biomechanics - Mechanical Properties of Living Tissue, Springer-Verlag by Prof. Sergio Alunni: W. H. Brown “Introduction of Organic Chemistry”, Saunders College Publishing, 1997. J. McMurry “Fundamentals of Organic Chemistry”, Brooks/Cole Publishing Company, third edition, 1994 Wadsworth. by Prof. Alceo Macchioni: Mahan/Myers “University Chemistry”, The Benjamin/Cummings Publishing Company, Inc., 1987. by Prof. José Maria Kenny: J. B. Park, Biomaterials-an Introduction, Plenum Press Y. C. Fung, Biomechanics - Mechanical Properties of Living Tissue, Springer-Verlag by Prof. Magdolna Szente (Physiology): 1) D Randall, W Burggren and K French "Eckerts animal physiology, mechanisms and adaptations", 4th ed, Freeman, New York, 1997. A very good textbook. Heavy emphasis on nerve, sensory and muscle physiology. Suitable for basic and advanced undergraduate courses. 2) P Willmer, G Stone and I Johnston "Environmental physiology of animals", Blackwell, Oxford, 1999. This is a new and very good book, excellent for the environment point of view. 3) K Schmidt-Nielsen "Animal physiology, adaptation and environment"; 5th ed, Cambridge University Press, Cambridge, 1997. A very good textbook. Very well written, but often too superficial. Suitable for basic undergraduate courses. 4) R W Hill and G Wyse "Animal physiology", 2nd ed, Harper Collins, New York, 1989. A good text, but becoming outdated. The figures are good, but too few and not in color. Lacks summaries. 5) P C Withers "Comparative animal physiology", Saunders, Fort Worth, 1992. A comprehensive text, about 1000 pages. Suitable for postgraduates. 6) I Kay "Introduction to animal physiology", Bios, Oxford, 1998. Very short, only about 200 pages. by Prof. Peter B. Gahan: Possible books for the Cell biology: Molecular Cell Biology by Lodish,H, Baltimore, D., Berk, P., Zipursky, SL., Matsdaira, P., Darnell, J. 4th Edition 2000. Scientific American Books. Fundamentals of Biochemistry: Voigt D., Voigt JG., Pratt CW. 1999 Wiley A textbook of Histology: Bloom W., Fawcett DW Sanders

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INDEX The University of Perugia

General Description Health and Insurance How to reach Perugia Useful Addresses “Job Creation Oriented Biotechnology” International First level Degree Work Plan of the First Year 2001/2002 Modules Program

Animal Biotechnology & Tissue Engineering- optional Biochemistry Bioethics Bioinformatics Biomaterials and Biocompatibility Biophysics Biotechnological Processes Business & Project Management Cell Biology & General Histology Cell Culture Computers & Biostatistics General and Inorganic Chemistry

General Physiology Genetics Food Processing – optional Immunology Industrial Simulation & Case Study Instrumental Analysis Microbiology MOLECULAR BIOLOGY Molecular & Genetic Diagnostics Organic Chemistry Patent & Law Pharmaceutical Biotechnology & Drug Engineering- optional Pharmacology & Toxicology Physical and mathematical fundamentals for biotechnology Plant Biotechnology - optional Quality Control & Assurance Attachment 1 Attachment 2 Textbooks Suggested “Aldo Capitini” Institute

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Index