Molecular Life Science

M.Sc. Molecular Life Science / University of Luebeck / Module Handbook 03/2010

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Molecular Life Science

M.Sc. Module Handbook

Universität zu Lübeck


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Content Cell biology and its relevance in disease development and therapy 4

Basics of Cell- and Molecular Biology for Virology 4 Medical Cell Biology I 6 Medical Cellbiology II 8 Biology of Infections 11

Structure Biology and its application in Pathogenesis and Therapy 12 Structure Analysis 12 Molecular Pathomechanisms and Strategies for Therapy 15 Drug Science 16 Basics of Membrane Biophysics 16

Profile Competences 16 Biomathematics / Molecular Bioinformatics 16 General virology and biosafety 16 Biophysics of Ionising Radiation and Radiation Safety 16 Ethics of Sciences and Scientific Writing 16

Practical Course – structure and procedure 16

Skills of the Practical Courses 16

Module: Consolidating in Molecular Life Science (Optional Programme) 16

Optional Programme Cell biology 16 Neurogenetics: Mutations, pathology and diseases 16 Intracellular membrane traffic – molecular mechanisms and approaches 16 Intracellular Topogenesis of Proteins - Concepts and Experimental Methods 16 Experimental Immunology 16 Functional anatomy of lymphatic Organs 16 Regulation of Gene Expression 16 Neural Differentiation of Progenitor Cells 16 Optional Programme Cell biology 16 Characterisation and relevance of DNA-repair for tumour development 16 Validation and quantification of miRNAs in malignant lymphomas 16

Optional Programme Structure Biology 16 Mass Spectrometry of Biomolecules 16 Special Topics of Biochemistry: Lipids, Glycolipids and structure-related membrane components, Oligo-, Polysaccharids and Glycoproteins 16 Biochemistry of Transition metals 16 NMR and drug design 16 Molecular Dynamics 16 Nucleic acid drugs 16 Structural Aspects of Protein biosynthesis 16 Modern Optical Techniques in Biomedicine and Biotechnology 16 Mechanisms in Photobiology and Photomedicine 16 Lighten up the dark: Modern fluorescence methods in structural biology 16 Computational methods for lead identification and optimization 16 Strategies of Antiviral Drug Discovery 16 Isolation, synthesis and characterisation of natural products 16

Master Thesis 16


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Preliminary remarks

Teaching method:

The teaching method specifies the teaching method being used in each course respectively.

Semester work-load (weekly hours) and expenditure of work:

The semester work-load is based on the assumption that an average term consists of 15 weeks.

One credit-point is equivalent to 30 hours of studies (lectures, seminars, practical courses or private study).

Literature - Required reading:

The list of recommended literature may be incomplete. A reading-list is recommended by the lecturers at the beginning of each course.

Structure and procedure of Practical Courses:

The students have to attend two Practical Courses. They include the participation in a current project and the execution and submission of the students´ own personal project related to the current project.

Each summer semester, all current available projects are submitted to the Prüfungsausschuss by all par-ticipating institutes and will then - as far as is possible.- be assigned to the students according to their pre-ferences. During the Practical Courses the students shall learn at least 4 different methods (refer to list). The Practical Courses cannot all take place in one and the same institute.

Optional Program / Optional Courses:

Apart from the compulsory courses the students may choose from a range of elective courses. If a student chooses an elective course from the range of courses offered by the University of Lübeck´s study program, the student´s participation in the course and his / her passing its examination will be documented in the Diploma Supplement.

Procedure of the Optional Programme:

The students may choose their subjects from a range of courses being updated at the beginning of each summer semester. The “Studiengangskoordinator” is responsible for making any necessary adjustments concerning the assignation of the courses.


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Cell biology and its relevance in disease development and therapy

Module: Basics of Cell- and Molecular Biology for Virology

Topic: Basics of Cell- and Molecular Biology for Virology

Semester: 1. Semester, only WS

Responsible instructor: Prof. Dr. E. Hartmann

Topic A: Cell Biology

Instructor A: Prof. Dr. E. Hartmann

Topic B: Molecular Virology

Instructor B: Prof. Dr. N. Tautz, Prof. Dr. R. Hilgenfeld, Dr. J. Mesters

Language: German, English

Part of the Curriculum: MLS / Master / Requisite Subject

Teaching method / atten-dance requirements:

Lecture: each course 2 WH (total 4 WH)

Workload: 60 h presence and 120 h private study

ECTS-Points: 6

Prerequisites: Bachelor degree in Molecular Life Sciences or in related fields

Goals: Part A Cell Biology:

1. Extended knowledge about the operation of cells and their intracellular compartments

2. Basic knowledge about the inventory of RNA-species in cells

3. Basic understanding on the way how viruses and other intracellular pathogens re-programme cellular mechanisms

Part B Molecular Virology:

1. Detailed knowledge on the interaction between viruses and their host cells

2. Details on virus structure and replication mechanisms as well as on derived anti-viral strategies

3. Pathogenic processes and virus-host interactions in virus infections

Content: Part A Cell Biology:

1. Membrane-surrounded compartments (B)

2. Membrane-surrounded compartments (C) The secretory pathway

2. 1. The Golgi apparatus

2. 2. Exocytosis

2. 3. The endo-/lysosmal compartment

2. 4. Caveosomes

2. 5. Membrane blebbing and Ectosomes

2. 6. Transport of lipids

2. 7. On the evolution of the secretory pathway

3. Cellular fusion, cytokinesis and organellar inheritence

4. RNA-metabolism


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1. Viral and cellular receptors for virus-cell interaction as well as their inhibition by inhibitors

2. Detailed molecular mechanisms of genome replication from selected virus families (focussed on RNA viruses)

3. Host factors and their function in viral genome replication on the basis of selected examples

4. Structural biology of viruses and its application for anti-viral therapy

5. Basics of viral pathogenesis

6. Viral strategies against the innate immune system

Type of examination: One written examination

One written examination on both parts (Cell Biology and Molecular Virology), each valued 50%.

Literature: Part A Cell Biology:

Lodish - Molecular Cell Biology

Alberts - Molecular Biology of the Cell


Molekulare Virologie: Modrow, Falke, Truyen, ISBN 3-8274-1086-X, Verlag/Hersteller: Spektrum Akademischer Verlag, Dezember 2002, Umfang/Format: XVIII, 734 Seiten, Illustrationen, graphische Darstellungen, 25 cm

Principles of Virology: Molecular Biology, Pathogenesis, and Con-trol of Animal Viruses: S. J. Flint, L. W. Enquist, V. R. Racaniello, American Society Microbiology, December 2003

As well as all scientific articles and journals


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Module: Medical Cell Biology I

Topic: Basics of Immunology

Semester: 1. Semester

Responsible instructor: Prof. Dr. med. J. Köhl; Prof. Dr. rer. nat. R. Manz

Instructors: Prof. Dr. med. J. Köhl; Prof. Dr. rer. nat. R. Manz; Dr. P. König and assistants

Language: German/English



Lecture / 2 WH

Seminar / 2 WH


ECTS-Points: 6

Prerequisites: BSc in Molecular Life Science or in related fields

Goals: 1. Basic Concepts in Immunology

2. The Immune System in Health and Disease

3. Immunological Methods

4. Improvement of professional presentation of scientific data

Content: Lecture:

1. Introduction and Overview

2. Cells of the innate immune system

3. Pathogen recognition by the innate immune system

4. Complement and inflammation

5. Introduction to the adaptive immune system

6. Antigen presentation and T cell activation

7. Immunological memory

8. Immune system and infection I: bacteria, worms, fungi

9. Immune system and infection II: viruses

10. Signal transduction in immune cells

11.Tissues and organs of the immune system; homing

12. Immunpathogenesis I: allergy and asthma

13. Immunpathogenesis II: autoimmune diseases

14. Immune privileged organs

15. Hematopoietic stem cells and hematopoiesis

Seminar:

1 PCR

2. Phage Display

3. ELISA/ELISPOT

4. Flow cytometry I: FACS analysis


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5. Flow cytometry II: MACS/FACS sort

6. Flow cytometry III: MACS/FACS practise at the ISEF

7. Conventional and confocal microscopy

8. Analysis of signalling pathways

9. Analysis of migration: transwell and adhesion assays

10. 2-photon microscopy

11. Animal models in life science

12. Genetically modified mice I: conventional transgenic and KO mice

13. Genetically modified mice II: conditional KO and knock in mice

14. Experimental and therapeutic biologics

Type of examination: Regular attendance, seminar lecture, written and oral examination

Literature: Immunology: Janeway, Travers, Walport, Shlomchik, Spektrum Akademischer Verlag, Gustav Fischer

Original and review articles


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Module: Medical Cellbiology II

Prerequisite for the certificate is the attendance of 3 courses; the attendance of further presentations is optional. Students who have attended more than 3 courses successfully may choose which course should be taken into the module account.

Semester: 2. Semester, only SS

Responsible instructor: PD Dr. med. J. Brinckmann

Topic A: Molecular Oncology

Instructors A: Prof. Dr. med. H. Merz, Prof. Dr. hum. biol. H.-W. Stürzbecher,

PD. Dr. rer. nat. C. Zechel

Topic B: Molecular Endocrinology

Instructors B: Prof. Dr. med. W. Jelkmann

Topic C: Tissue regeneration

Instructors C: PD Dr. J. Brinckmann

Topic D: Neurobiology

Instructors D: Prof. Dr. med. C. Klein, Prof. Dr. rer. nat. C. Zühlke

Topic E: Molecular biology of the cardiovascular system

Instructors E: Prof. Dr. med. J. Weil

Language: German



Lecture / each course 2 WH = 6 WH (3 chosen courses)


ECTS-Points: 8


Goals: Part A Molecular Oncology:

1. Understanding the concepts in oncoclogy; principles in tumour initiation, tumour progression and relapse

2. Understanding the significance of repair mechanisms for tumour formation and therapy

3. Understanding the molecular and cellular features of tumours (selected examples such as glioma, melanoma, leukemia and lymphoma)

Part B Molecular Endocrinology:

1. Understanding the regulation of hormonal production with emphasis on the pancreatic gland, thyroid gland, adrenocortical gland and kidney

2. Understanding the main mechanisms of hormonal actions.

3. Knowledge of established and novel strategies for the treatment of diseases of specified hormone producing organs

Part C Tissue regeneration:

1. Understanding of molecular and morphological entities in the


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assembly of extracellular matrix of different origins

2. Understanding of (patho)physiological mechanisms in tissue regeneration

Part D Neurobiology:

1. Acquiring basic skills in neuroanatomy, neuroimaging, electrophysiology and neurogenetics

2. Understanding pathophysiology using select examples of neurogenetic diseases

Part E Molecular biology of the cardiovascular system

1. Understanding the (patho-) physiological mechanisms in cardiovascular diseases

2. Understanding molecular and genetic characteristics of selected cases of cardiovascular diseases

Content: Part A Molecular Oncology:

1. Oncology from the view of the pathologist; early and recent concepts in oncology; tumour stem cells; defects in DNA-repair systems as a cause for tumorigenesis

2. Biochemical, as well as cellular and molecular characteristics and features of tumours (melanoma, glioma, hematopoetic tumours)

3. Concepts of prevention and therapy of tumours (melanoma, glioma, hematopoetic tumours)

4.Chromatin: Mutations, translocations, methylation, telomere and mitosis defects Epidemiology and „Lifestyle“ in the carciogenesis of lymphoma


1. The hormone-producing organs pancreatic gland, thyroid gland, adrenocortical gland and kidney

2. Principles of the structure/function relation of hormones

3. Hormone receptors and signal transduction pathways

4. Diseases and therapeutic options in patients suffering from diabetes mellitus, hypo- or hyperthyroidism, adrenal gland failure, disturbances of calcium homeostasis, renal anemia

Part C Tissue regeneration:

1. Introduction / Morphological structures

2. Biosynthesis and function of matrix proteins (collagens, non-collagenous proteins)

4. Composition and function of basement membrane

5. Tissue regeneration (embryonic, adult) and fibrosis

6. Tissue substitutes


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1. Introduction into neuroanatomy

2. Modern methods of structural, functional and metabolic neuroimaging

3. Electrophysiology in diagnostics of neurological diseases and understanding basic neurobiologic mechanisms (EEG, EMG, TMS) selecting neurogenetic diseases: dystonia-parkinsonism syndromes, repeat disorders

4. Linkage analyses, gene cloning, genetic association, molecular neurobiology

5. Selecting neurogenetic diseases: dystonia-parkinsonism syndromes, repeat disorders


1. Introduction into cardiovascular medicine

2. Molecular and genetic changes in chronic heart failure

3. Molecular and genetic changes in atherosclerosis

4. Molecular and genetic changes in angiogenesis

Type of examination: Written examination

Literature: Part A Molecular Oncology:

Textbooks (Schlegel et al, Neuroonkologie, Thieme; Knippers: Mo-lekulare Genetik, Thieme; Passarge und Wirth: Taschenatlas Hu-mangenetik, Thieme)

Recent original papers and overviews


Goodman and Gilman´s The Pharmacological Basis of Therapeu-tics: Brunton L, J Lazo, K Parker, McGraw-Hill Comp. Inc., New York, 11th edition, 2005

Part C Regenerative medicine and connective tissue disor-ders:

Connective Tissue and its heritable disorders. Edited by P. Royce and B. Steinmann, Wiley-Liss, 2002

Topics in Current Chemistry, 247, Collagen Primer in Structure, Processing and Assembly, ed by Brinckmann, Notbohm, Müller, 2005


Textbooks


Braunwald's Heart Disease: A Textbook of Cardiovascular Medi-cine ISBN 1416041060 / 9781416041061 · 2304 Pages · 1500 Il-lustrations, Saunders · 8th edition published November 2007


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Module: Biology of Infections

Topic: Specific Topics of Infection Biology


Responsible instructor: Prof. T. Laskay

Instructors: Prof. T. Laskay, Prof. Dr. med. W. Solbach,

Prof. Dr. rer. nat. C. Hölscher, PD Dr. rer. nat. N. Reiling,

Prof. Dr. med. J. Knobloch, Prof. Dr. rer. nat. U. Seitzer,

PD Dr. rer. nat. S. Niemann,

Language: English, German



Lectures / 2 WH

Seminar / 2 WH


ECTS-Points: 6


Goals: 1. Detailed knowledge of infectious agents, infectious diseases and their pathomechanisms.

2. Detailed understanding of antimicrobial defence mechanisms at the cellular and molecular level. Understanding the mechanisms of vaccination and immune deficiencies.

3. Knowledge of in vivo and in vitro techniques of infection biology.

Content: Lecture:

1. Infectious diseases, viral, prokaryotic and eukaryotic infectious agents, parasites, zoonotic diseases

2. Molecular mechanisms of antimicrobial chemotherapy, mechanisms of resistance against antiviral and antibacterial drugs

3. Intracellular pathogens, molecular mechanisms of intracellular survival, Mycobacteria

4. Antimicrobial immune mechanisms, compartments and regulation of antimicrobial defence, allergy

5. Immune therapy and vaccination, mechanisms of the induction of specific T-cell and B-cell mediated protective immunity, adjuvants, DNA vaccines

6. Experimental techniques in the infection biology, in vitro and ex vivo methods, experimental animal models of infectious diseases, gene knock-out mice, gene manipulated infectious agents

7. Immune deficiencies, immunosuppressive chemotherapy and its consequences, retroviruses, HIV-AIDS

8. Epidemiology of infectious diseases, zoonoses

Type of examination: Seminar lecture and written examination

Literature: Textbooks, review articles


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Structure Biology and its application in Pathogenesis and Therapy

Module: Structure Analysis


Responsible instructor: Prof. Dr. T. Peters

Topic A: Crystallography

Instructors A: Prof. Dr. R. Hilgenfeld, Dr. J. Mesters,

external visiting lecturers from home and abroad

Topic B: NMR-Spectroscopy

Instructors B: Prof. Dr. T. Peters, PD Dr. T. Weimar, Dr. T. Biet

Topic C: Single Molecule Methods

Instructors C Prof. Dr. C. Hübner

Topic D: Microscopy: techniques and applications

Instructors D Prof. Dr. R. Duden

Language: German / English



Lecture / each course 2 WH (total 4 WH)


ECTS-Points: 6

Prerequisites: BSc in Molecular Life Science or related fields

Goals: Part A Crystallography:

1. Expansion of the basic diffraction theory

2. Practical exercises in the X-ray laboratory

3. X-ray analysis in the drug discovery process

Part B NMR-Spectroscopy:

1. Advanced theoretical principles of NMR and their experimental application for the study of biological macromolecules (product spin operator formalism, Fourier transform spectroscopy)

2. Application of the product spin operator formalism (COSY, INEPT)

3. Chemical exchange and NMR experiments for the analysis of protein-ligand interactions

Part C Single Molecule Methods:

1. Basic knowledge of single-molecule methods

2. Knowledge of possibilities/limits of the method

3. Competence in the choice of the right method

Part D Microscopy: techniques and applications:

1. Basics of light and fluorescence microscopy and electron microscopy

2. Detailed knowledge of methods for labelling and visualization


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of proteins and subcellular compartments

3. Applications of live cell imaging, in vivo imaging, and quantitative fluorescence techniques

Content: Part A Crystallography:

1. Crystal growth, precipitant and phase diagram, crystal morphology, symmetry and space groups, crystallogenesis

2. X-rays, X-ray sources, X-ray diffraction, Bragg's law, reciprocal lattice and Ewald-sphere construction

3. X-ray diffraction by electrons, Fourier analysis and synthesis

4. Protein structure determination by X-ray diffraction, crystallographic phase problem, Patterson map, molecular replacement (MR), multiple isomorphous replacement (MIR), multi-wavelength anomalous diffraction (MAD)

5. Crystallography and the drug discovery process: studying protein-ligand interactions

6. Practical exercises at the X-ray generator and at the computer

7. Site visit at the Synchrotron DESY (Hamburg)


1. Analysis of the solution structure of proteins using a peptide as an example (including a practical)

2. Fourier transformation and multidimensional spectroscopy

3. Introduction into the product spin operator formalism

4. Applications of the product spin operator formalism

5. Protein-ligand interactions with NMR


1. Basics of single-molecule fluorescence

2. Basics of correlation analysis

3. Photo physics and chemistry of SM FRET

4. Conformational dynamics with SM FRET

5. Protein folding with SM FRET

6. Optical tweezers: Basics and instrumentation

7. Optical tweezers: Applications with motor proteins

8. Force spectroscopy: Basics and applications


1. Introduction to microscopy, confocal microscopy, 2-photon microscopy

2. Light sources, detectors, optical elements: lenses, mirrors and filters

3. Fluorescence as a phenomenon, Fluorecent dyes, GFP and fluorescent proteins


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4. Live cell microscopy, in vivo imaging: methods, applications, and limitations

5. Visualizing/identifying cell components using fluorescence techniques

6. Protein-protein interactions in living cells: FRET, FLIM, FCS

7. Photo-activatable and photo-switchable proteins, fluorescent timers, biosensors

8. Advanced and super-resolution 3D-Microscopy: STED, PALM; quantitative fluorescence techniques, flow cytometry

9. Electron microscopy: TEM, SEM, immunogold label; a survey of ultrastructure, correlative EM/light microscopy

Type of examination: One written examination

One written examination with all parts, each valued 25%.

Literature: Part A Crystallography:

Principles of Protein X-ray Crystallography: Jan Drenth, Spinger Science+Business Media, LLC, New York


James Keeler: Understanding NMR Spectroscopy, Wiley

Horst Friebolin: Ein- und zweidimensionale NMR-Spektroskopie. Eine Einführung, Wiley-VCH

Spin Dynamics - Basics of Nuclear Magnetic Resonance: M. H. Levitt, Wiley-VCH

The Nuclear Overhauser Effect in Structural and Conformational Analysis: D. Neuhaus & M. P. Williamson, Wiley-VCH

Basic and survey articles


Joseph R. Lakowicz: Principles of Fluorescence Spectroscopy


Literature: see the following WEB links:

http://micro.magnet.fsu.edu/primer/index.html

http://www.microscopyu.com/smallworld/

http://www.olympusmicro.com/


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Module: Molecular Pathomechanisms and Strategies for Therapy

Topic: Molecular Pathomechanisms and Strategies for Therapy


Responsible instructor: Prof. Dr. T. Restle

Instructors: Prof. Dr. T. Restle, Dr. R. Kretschmer Kazemi-Far

Language: German



Lecture / 4 WH


ECTS-Points: 6


Goals: 1. General mechanisms of tumour development

2. Mechanisms of viral carcinogenesis by selected mammalian RNA and DNA viruses

3. DNA repair and tumour development

4. Correlation of apoptosis and tumour development

5. The role of tumour suppressor genes

6. Impact of metastasis and neoangiogenesis on tumour progression

7. Diagnostic and therapeutic approaches

Content: 1. Oncogenes and their viral relatives

2. Correlation of tumour development and DNA repair defects

3. Pathways, regulation and pathological relevant deregulation of apoptosis

4. Correlation of cellular signalling cascades and tumour development

5. Molecular basis of angiogenesis and cell migration

6. Tumour diagnostic

7. Rational concepts in tumour therapy


Literature: Principles of Virology: Molecular Biology, Pathogenesis, and Con-trol of Animal Viruses, S.J. Flint et al., 850 Seiten - American Soci-ety Microbiology, Dezember 2003, 2nd, ISBN 1555812597

Biochemie und Pathobiochemie von Georg Löffler, Petro E. Pet-rides, 1267 Seiten - Springer, Berlin, September 2002, ISBN 3540422951

Handbuch der Molekularen Medizin, Bd. 1: Molekularbiologische und Zellbiologische Grundlagen von Detlev Ganten, Klaus Ruck-paul, Springer, Berlin, Oktober 2002, ISBN 3540432078

The Biology of Cancer von Robert Weinberg, Garland Science; 1 edition (June 9, 2006), ISBN-10: 0815340788

Current research and review articles


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Module: Drug Science


Responsible instructor: Prof. Dr. T. Peters

Topic A: Pharmacology and Toxicology

Instructors A: PD Dr. O. Jöhren, PD Dr. M. Tegtmeier, Prof. Dr. H. Terlau

Topic B: Drug Design

Instructors B: Prof. Dr. T. Peters, Dr. H. Peters, PD Dr. T. Weimar,

Prof. Dr. T. Restle, Dr. A. Meschalchin, Prof. Dr. R. Hilgenfeld,

Prof. Dr. H. Steuber, external lecturers from the industry




Lecture / each course 2 WH (total 4 WH)


ECTS-Points: 6


Goals: Part A Pharmacology and Toxicology:

The students will acquire knowledge in:

1. Effects of therapeutic drugs on the organism (Pharmacodynamics)

2. Time course of therapeutic drug concentrations in the organism (Pharmacokinetics)

3. Mechanisms of action of various substance classes

4. Isolation of novel substances

Part B Drug Design:

The students need to know:

1. Basic strategies of Drug Design.

2. The way from the target discovery to the drug. Techniques of rational Drug Design.

3. NMR and X-ray Crystallography as important tools for target monitoring and optimization

4. The relationship between chemical structure and effect and the techniques for theoretical prognosis and experimental tests, particular x-ray crystallography and NMR-experiments

5. The students should know the borders of x-ray crystallography and NMR-experiments.

Content: Part A Pharmacology and Toxicology:

1. Pharmacodynamics I

1.1 Dose-response curves (Emax, EC50)

1.2 LD50, Therapeutic Range

1.3 Mechanisms of Action (specific, nonspecific)

1.4 Sites of Actions (Receptors, Enzymes, Membranes)


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2. Pharmacodynamics II

2.1 Receptor theory, Receptor binding assays

2.2 Types of physiological Receptors, Signal transduction

2.3 Agonists - Antagonists

2.4 Forms of Antagonism (competitive, non-competitive)

3. Pharmacokinetics I

3.1 LADME-Concept (Liberation, Absorption, Distribution, Metabolism, Elimination)

3.2 Sites of Absorption

4. Pharmacokinetics II

4.1 Pharmacokinetic Parameters (e.g. Half-Life, Rate of Elimination, Bioavailability, AUC, Bioequivalence, Volume of Distribution, Clearance)

4.2 Mathematical Pharmacokinetics

4.3 Pharmacokinetics in the elderly

5. Endocrine Pharmacology I (Steroids)

5.1 Structure of GR- und MR-selective synthetic Gluco- und Mineralocorticoids

5.2 Estrogens, selective Estrogen-Receptor-Modulators (SERMs), Gestagens, Androgens

6. Endocrine Pharmacology II

6.1 Thyroid hormones (Levothyroxine, Liothyronine)

6.2 Antithyroid Drugs (Inhibitors of Iodisation, Inhibitors of Iodination)

6.3 Genetically engineered Insulins

6.4 Oral antidiabetics (±-Glucosidase-Inhibitors, Biguanide derivatives, Sulfonylurea derivatives /-analogs, PPAR≥-Agonists, GLP-1-Analogs, DPP-IV-Inhibitors)

7. Reverse Pharmacology: From Genes to Drugs

7.1 The Human-Genome-Project

7.2 Orphan-Receptors and Isolation of endogenous Ligands

7.3 Development of novel Substances and their potential pharmaceutical Role exampled for Orexines

8. Ion channel pharmacology I

8.1 Electrical excitability of cells

8.2 Na-, K-, Ca-channels

8.3 Local anesthetics, antiarrhytmic drugs

9. Ion channel pharmacology II

9.1 Studies on structure/function relationships

9.2 Binding sites on ion channels

9.3 State-dependence of drug-target interaction

10. Receptor pharmacology I

10.1 Synaptic transmission


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10.2 Synaptic plasticity (pre- and postsynaptic)

10.3 Transmitters (Glu, Ach, GABA, dopamine, noradrenalin)

11. Receptor pharmacology II

11.1 Sympathetic division

11.2 Parasympathetic division

11.3 Muscle relaxants

12. Peptide toxins

12.1 Biological importance of peptide toxins

12.1 Peptide-target interaction

12.2 „mutant cycle“ analysis

Part B Drug Design:

1. Concepts in Drug Design

1.2 From serendipity to structure based drug design

1.3 Molecular principles of drug-target interactions

1.4 Tools in Drug Design: HTS, databases etc.

1.5 Fragment based approaches

1.6 Definition and use of log p values

1.7 Library Filtering

1.8 QSAR

2. NMR experiments for Drug Design

2.1 Ligand based techniques

2.1.1 Saturation Transfer Difference NMR

2.1.2 Transfer NOE experiments

2.4.3 Other ligand based techniques

2.2 Protein based techniques

2.2.1 HSQC based screening

2.2.2 Cross saturation

3. Case Study: Omeprazole vs. Tamiflu

3.1 Influenza infection

3.2 Structure based design of neuraminidase inhibitors

3.3 Synthetic routes to tamiflu

3.4 Heart burn

3.5 Discovery of omeprazole

3.6 Synthetic route to omeprazole

3.7 Patent issues

4. Chemical Synthesis of Drugs - Combinatorial Approaches

4.1 Peptide synthesis

4.2 Solid phase synthesis

4.3 Combinatorial libraries


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5. Drug Discovery - An Overview

5.1 The Nature of Drugs

5.2 History of Drug Discovery

5.3 Serendipity and Drug Discovery

5.4 Modern Drug Discovery and Development

5.4.1 Stages, Costs and Attrition Rates

5.4.2 Productivity Gaps - Why do drugs fail?

5.4.3 New challenges for drug discovery

6. Target Identification and Validation

6.1 Target Identification

6.1.1 Sequence-structure homology recognition

6.1.2 Molecular and systems approaches

6.1.3 Genomics

6.1.4 Proteomics

6.1.5 Genetic association

6.1.6 Forward/reverse genetics

6.1.7 Chemical genetics

6.1.8 Cell and animal disease models

6.1.9 Predicting protein druggability

6.2 Use of oligonucleotides for target validation

6.3 Identifying targets for bioactive molecules

6.3.1 Affinity chromatography

6.3.2 Photo-affinity and chemical cross-linking

6.3.3 Protein microarrays

6.3.4 Phage display

6.3.5 mRNA display

6.3.6 Yeast 3-hybrid screening

6.3.7 Drug-induced haploinsufficiency

7. X-ray Crystallography in Drug Design

7.1 Cost and value of 3D structure in drug design

7.2 Lead optimization

7.3 Sequence-structure homology recognition

7.4 X-ray-based fragment screening

7.5 Limitations of X-ray methods

7.6 Data quality and resolution

7.7 Crystallization artifacts

7.8 Ligand soaking and co-crystallization

8. Structure-based drug design - Principles and Methods

8.1 Overview of the process

8.2 Evaluating the target structure

8.3 Identifying the target site


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8.4 Computer-based design methods

8.4.1 Inspection

8.4.2 Virtual screening

8.4.3 De novo methods

8.5 Protein and ligand flexibility

8.6 Solvent effects

8.7 Drug lead evaluation

9. Case studies in structure-based drug design

9.1 From snake venom to billion-dollar drug - the Captopril story

9.2 Flu and Bird flu: The rational design of Tamiflu

10. Combinatorial approaches to identify effective nucleic acid leads and drugs

10.1. Relevant classes of nucleic acids

10.2. Theoretical considerations

10.3.Combinatorial strategies - SELEX, affinity vs kinetics

10.4. Example: Development of Spiegelmers

11. Oligonucleotides

11.1 Oligonucleotides in clinical studies

11.2. Nucleic Acid Delivery I

11.3 Oligomeric nucleic acids as potential therapeutics/diagnostics

12. Nucleic Acid Delivery II

12.1 Comparison of different nucleic acid delivery techniques

12.2 Non-viral nucleic acid carrier

12.3 Fate of nucleic acids taken up by endocytosis

12.4 Experimental approaches to correlate uptake and efficacy of nucleic acid drugs

Type of examination: One written examination with on both parts (Pharmacology and Toxicology, Drug Design), each valued 50%

Literature: Part A Pharmacology and Toxicology:

Goodman & Gilman's The Pharmacologic Basis of Therapeutics - by Brunton L, Lazo J, Parker K, 11th Ed., McGraw-Hill 2006, ISBN 0071422803

Color Atlas of Pharmacology, by Lüllmann H, Mohr K, Hein L, 3rd Ed., Thieme 2005, ISBN 313781703X

Part B Drug Design:

Wirkstoffdesign: G. Klebe, Spektrum-Verlag, Heidelberg, 2009, ISBN 978-3-8274-2046-6

Modern Methods in Drug Discovery: A. Hillisch & R. Hilgenfeld, Birkhäuser, Basel, Boston, Berlin 2003, ISBN 3-7643-6081-X

Basic and survey articles for both lectures


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Module: Basics of Membrane Biophysics

Topic: Structure and Function of Membranes


Responsible instructor: PD Dr. T. Gutsmann

Instructors: PD Dr. A. Schromm, PD Dr. J. Andrä




Lecture / 2 WH

Exercise / 1 WH


ECTS-Points: 4


Goals: The students will achieve knowledge in:

1. Constituents and composition of biological membranes

2. Physical role and function of membrane lipids and proteins

3. Mechanical and electrical properties of membranes

4. Various methods to investigate reconstituted and natural membranes

Content: 1. Importance and function of cell membranes: structure, physical function and dynamic models

2. Basics of the membrane components

3. Thermodynamic self-assembling of lipids and reconstitution techniques

4. Transmembrane and intrinsic membrane potentials

5. Mechanical properties of lipid membranes

6. Physical basics of membrane transport mechanisms

7. Investigations using lipid monolayer

8. Electrical and optical experiments using planar lipid bilayers

9. Examples for interaction mechanisms between peptides/ proteins and planar membranes

10. Spectroscopic methods on membranes and membrane proteins

11. Light and force microscopy on membranes and membrane proteins


Literature: Physikalische Chemie und Biophysik: G. Adam, P. Läuger, G. Stark, Springer Verlag, 4. Auflage 2003

Methoden der Membranphysiologie: W. Hanke, R. Hanke, Spek-trum Akademischer Verlag, Auflage 1997


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Profile Competences

Module: Biomathematics / Molecular Bioinformatics

Prerequisite for the certificate is the attendance of one course. The attendance of the second course is optional. Students who have successfully attended both courses may choose which one should be taken into the module account.


Responsible instructor: Prof. Dr. T. Martinetz, Prof. Dr. J. Prestin

Topic A: Biomathematics

Instructors A: Prof. Dr. J. Prestin, PD Dr. K. Keller

Topic B: Molecular Bioinformatics

Instructors B: Prof. Dr. T. Martinetz, Dr. S. Möller



CLS / Bachelor / Requisite Subject

MIW / Bachelor / Optional Subject

Informatics / Bachelor / Requisite Subject for Bioinformatics


Lecture / 2 WH

Exercise/ 2 WH (for Master MLS)


ECTS-Points: 5


Goals: Part A Biomathematics:

1. Basics of the theory of ordinary differential equations

2. Treatment of the application of differential equations to models in biology, chemistry and medicine

Part B Molecular Bioinformatics:

1. Computational and statistical means for the analysis of biological high-throughput data

2. Formal representation of knowledge in biological databases

3. Application of Statistical Physics to computationally model biological systems

Content: Part A Biomathematics:

1. Fundamentals of differential equations

2. General solvability

3. Systems of linear differential equations of first order


1. Introduction to current biological databases

2. Information and entropy in biological sequences


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3. DNA-microarrays: data acquisition and data analysis

4. Evolutionary algorithms and stochastic optimisation

5. Machine learning for biological problems

Exercises:

Exercises with regard to the topics of the lecture; presentation, interdisciplinary teamwork


Literature: Part A Biomathematics:

Durbin, Eddy, Krogh, Mitchinson: Biological sequence analysis

Wong: The Practical Bioinformatician

Setubal, Meidanis: Introduction of Computational Molecular Biol-ogy


Bioinformatik: Sequenz-Struktur-Funktion; Rauhut, Reinhard, Wi-ley-VCH, Weinheim, 2001, ISBN 3-527-30355-3

Thermodynamik und Statistische Physik: Schnakenberg, Jürgen, Wiley-VCH, 2001, ISBN 3-527-40362-0.


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Module: General virology and biosafety

Topic: General virology and biosafety


Responsible instructor: Prof. Dr. N. Tautz

Instructors: Prof. Dr. N. Tautz, PD Dr. H. Hennig




Lectures 2 WH

Exercise 2 WH (as block course of 2 weeks duration)


ECTS-Points: 4


Goals: 1. Systematics in virology and its molecular basis

2. Viral life cycles and replication strategies

3. Basic techniques in virology and virus diagnostics

4. Virological safety of blood products

5. Basics in “Gentechnikrecht” and “Biostoffverordnung”

6. Improvement of scientific communication skills in the English language

Content: Lecture:

1. History of virology

2. Virus taxonomy and structure

3. Virus morphology in overview

4. Viral life cycles (entry, assembly, budding)

5. Replication mechanisms

6. Viral evolution

7. Basic techniques in virology and methods of virus diagnostics

8. Blood-borne viruses and safety of blood products

9. Biosafety classification of viruses according to “Gentechnik-recht” and “Biostoffverordnung”

Exercises:

Exercises with regard to the topics of the lecture

Type of examination: Presentation in English, written examination

Literature: Principles of Virology: Molecular Biology, Pathogenesis, and Con-trol of Animal Viruses, S.J. Flint et al., 850 Seiten - American Soci-ety Microbiology, Dezember 2003, 2nd, ISBN 1555812597

Biochemie und Pathobiochemie von Georg Löffler, Petro E. Pet-rides, 1267 Seiten - Springer, Berlin, September 2002, ISBN 3540422951

Handbuch der Molekularen Medizin, Bd.1 : Molekularbiologische


25

und Zellbiologische Grundlagen von Detlev Ganten, Klaus Ruck-paul, Springer, Berlin , Oktober 2002, ISBN 3540432078



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Module: Biophysics of Ionising Radiation and Radiation Safety

Topic: Biophysics of Ionising Radiation and Radiation Safety


Responsible instructor: Prof. Dr. B. Matzanke-Markstein

Instructors: Prof. Dr. B. Matzanke-Markstein, Prof. Dr. H. Notbohm,

Prof. Dr. C. Hübner, PD Dr. B. Meller, Dipl.-Ing. H. Schönwald

Language: German



Lectures / 2 WH

Practical course / 2WH


ECTS-Points: 4


Goals: Certificate in radiation safety according to German law (StrSchV, RöV)

Acquisition of basic skills in dealing with radioactive materials and sources

Knowledge of ethical and socio-political aspects of applying ioniz-ing radiation

Content: Lecture:

1. Physics of ionizing radiation

2. Basic principles of dosimetry

3. Introduction to methods of radiation measurement

4. Radiation biology: principles of radiation damage, deterministic and stochastic effects, health risks caused by ionizing radiation

5. Radiation chemistry, handling of radioactive materials

6. Safety requirements in radionuclide laboratories

7. Application of radionuclides in biochemistry and molecular biology

8. Laws and regulations dealing with radiation safety

Laboratory course: (groups of 2)

1. Work with encapsulated and open radiation sources

2. Application of radiation safety measures for the design of experiments with α-, β- and γ-emitters

3. Contamination and incorporation, decontamination

4. Proper utilization of all equipment required for measurements of α-, β-, K-capture- and γ-radiation. Interpretation of spectra.

5. Application requirements for a position as radiation safety officer

Type of examination: Regular participation in the practical course, written examination

Literature: Textbooks, basic and survey articles


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Module: Ethics of Sciences and Scientific Writing

Topic: Ethics of Sciences and Scientific Writing


Responsible instructor: Prof. Dr. G. Sczakiel

Topic A: Ethics of Sciences

Instructors A: Prof. Dr. H. W. Ingensiep, Dr. K. T. Kanz

Topic B: Scientific Writing

Instructors B: Prof. Dr. G. Sczakiel




Part A Ethics of Sciences: Lectures / 2 WH

Part B Scientific Writing: Seminar / 2 WH


ECTS-Points: 7


Goals: Part A Ethics of Sciences:

1. Basic knowledge about philosophy of natural sciences

2. Understanding ethical dimensions of human action

3. Knowledge about relevant legal rules in Germany

4. Knowledge about current discussions in bioethics and research ethics

5. Capability to reflect on ethical problems concerning MLS

Part B Scientific Writing:

1. Analysis of the logical and formal structure of scientific publica-tions. Analysis of a specific original publication. Introduction into the ´peer-review process´.

2. Understanding the criteria underlying scientific posters. Preparation and presentation of a poster based on given experimental data.

3. Introduction into the writing of ´grant applications´ and the funding process of research projects. Writing a grant application on the basis of specified prior-work and scientific aims

Content: Part A Ethics of Sciences:

1. Basic positions in philosophy of natural sciences: foundations, methods, theory dynamics

2. Basic concepts of bioethics and metaethics: fundamentals, positions, problems

3. Research ethics: fundamentals, duties of researchers, ethics in clinical research

4. Laws and rules concerning scientific research: freedom of


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research, good scientific practice, legislation

5. Current topics concerning laws and ethics in MLS: Patenting of organisms, genetic diagnosis / gene tests, embryo protection act, stem cell research, experiments with animals and humans


1. Introduction into categories of scientific presentations

2. Analysis of scientific manuscripts and rules for their presentation

3. Preparation and presentation of scientific posters

4. Preparing a project proposal

Type of examination: Examination, oral participation, presentation.

The module is successfully graduated if both courses are passed

Literature: Part A Ethics of Sciences:

Bioethik. Eine Einführung: Düwell, Marcus; Steigleder, Klaus (Hrsg.)(stw; 1597), Frankfurt/Main: Suhrkamp Taschenbuch, 2003, ISBN 3-518-29197

Düwell, Marcus; Hübenthal Christoph; Werner (Hrsg.): Handbuch Ethik, 2. A. Metzler Stuttgart 2006, ISBN: 13-978-3-476-02124-3



Publications of virtual data


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Practical Course – structure and procedure

The students have to attend two Practical Courses. They include the participation in a current project and the execution and submission of the students´ own personal project related to the current project.

Each summer semester, all current available projects are submitted to the Prüfungsausschuss by all par-ticipating institutes and will then - as far as is possible.- be assigned to the students according to their pre-ferences. During the Practical Courses the students shall learn at least 4 different methods (refer to list). The Practical Courses cannot all take place in one and the same institute.

If the practical courses are taken externally (outside the University of Luebeck) the students have to choose a lecturer (see PO) from the University of Luebeck as a second supervising tutor.

Module: Practical Course I

Topic: s. overview Practical Course


Responsible instructor: Prof. Dr. Enno Hartmann

Instructors: s. overview Practical Course




Practical course / each 12 WH (2 units, each 8 weeks)

Workload: Each course 180 h presence and 60 h private study

ECTS-Points: 8


Passed all modules of the 1. Semester

Goals: 1. Extension of experimental work in two fields of Cell - and Structure Biology (called competences) in each course

2. Absorbing knowledge in documentation and presentation of scientific data (poster presentation)

3. Ability to work in a team

4. Getting lab experiences by working on real research projects

Content: See list Competences of Practical Courses and overview

Type of examination: The mark consists of: 25% practical instruction and 75% poster presentation marked by 3 examiners

Literature: Textbooks, lab instructions, basic and survey articles


30

Module: Practical Course II

Topic: s. overview Practical Course


Responsible instructor: Prof. Dr. Enno Hartmann

Instructors: See overview Practical Course




Practical course / each 12 WH (2 units, each 8 weeks)

Workload: Each course 180 h presence and 60 h private study

ECTS-Points: 8



Goals: 1. Extension the experimental work in two fields of Cell - and Structure Biology (called competences) in each course

2. Absorbing knowledge in documentation and presentation of scientific data (presentation with defence)

3. Ability to work in a team

4. Getting lab experiences by working on real research projects

Content: See list Competences of Practical Courses and overview

Type of examination: The mark consists of: 25% practical instruction and 75% scientific presentation marked by 3 examiners

Literature: Textbooks, lab instructions, basic and survey articles


31

Skills of the Practical Courses

Structural biology

S 1

Structure analytics of macromole-cules

S 2

Proteinexpression-and cleaning

S 3

Membranbio-physics

S 4

RNA-Technologies

S 5

Computer aided methods

Cristallography From bacteria cells Liposomes Expression and purification

Data base search / automation

NMR-Spectroscopy From eukaryotic cells

Synthetic biologi-cal membranes

mi-RNA, si-RNA, anti-sense - te-chniques

Computer languages

Mass-Spectrometry Ex situ-isolation Phosphoimaging

CD-Spectroscopy Chromatography- /Blot-techniques

Spectralphotometry

Fatty acid-, carbo-hydrate analytics

Proteinsequensing

Target-effector-interactions (SPR)

Cell biology

Z 1

Tissue culture/ Cell culture

Z 2

Cellphysiology and Cellbiochemistry

Z 3

Classical and moleculare Genet-ics

Z 4

Animal Physiol-ogy

Z 5

Microscopic Tech-niques

In vitro cellculture Proteintransports Bacteria, yeast- and cellgenetics

Ex vivo per-funded organs

Lightmicroscopy (incl. immuno-fluoreszenz)

Stem cell biology Signaltransduction Cytogenetics Animal experi-ments

Electronmicroscopy (TE- and raster)

Infection tests (vi-ruses, bacteria, parasites)

Cell metabolism Moleculargenetics (cloning, se-quensing, PCR, SSCP, mutagene-sis)

Immunhistochemistry, FACS, Tissue and gene arrays

Biocomposites Cellfree systems Genomanalysis In situ -hybridisation

Fotobiology


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Module: Consolidating in Molecular Life Science (Optional Programme)

Procedure of the Optional Programme

The courses are offered as a unit. They may take place either at the beginning or at the end of a semester or on a weekly basis for the whole length or part of the semester. The range of the courses and the teach-ing times are updated at the end of the summer semester. The “Studiengangskoordinator” is in charge of making adjustments concerning the assignation of the courses if necessary.

Optional Programme: Overview (as in WS 2009/10)

Cell Biology and its Application in Pathogenesis and Therapy

Titel ECTS Instructor No.

Neurogenetics: Mutations, pathology and diseases 3 Prof. Dr. C. Klein Z-A

Intracellular membrane traffic – molecular mechanisms and approaches

3 Prof. Dr. R. Duden Z-B

Intracellular Topogenesis of Proteins - Concepts and Ex-peri-mental Methods

3 PD Dr. K.-U. Kalies Z-C

Experimental Immunology 3 Prof. Dr. C. Hölscher Z-D

Functional anatomy of lymphatic Organs 3 Dr. K. Kalies Z-E

Regulation of gene expression 3 PD Dr. C. Zechel Z-F

Neural Differentiation of Progenitor Cells 3 PD Dr. C. Zechel Z-G

Characterisation and relevance of DNA-repair for tumour development

3 Prof. H.-W. Stürzbecher Z-H

Validation and quantification of miRNAs in malignant lymphomas 3 Prof. H.-W. Stürzbecher Z-I

Structural Biology and its Application in Pathogenesis and Therapy

Titel ECTS Instructor No.

Mass Spectrometry of Biomolecules 3 PD Dr. B. Lindner S-A

Special Topics of Biochemistry: Lipids, Glycolipids and struc-ture-related membrane components, Oligo-, Polysac-charids and Glycoproteins

3 Prof. Dr. O. Holst S-B

Biochemistry of Transition metals 3 Prof. Dr. B. Matzanke-Markstein

S-C

NMR and Drug Design 3 Prof. Dr. T. Peters S-D

Molecular Dynamics 3 PD Dr. H. Paulsen S-E

Nucleic acid drugs 3 Prof. Dr. G. Sczakiel S-F

Structural Aspects of Protein biosynthesis 3 Dr. J. Mesters S-G

Modern Optical Techniques in Biomedicine and Biotechnology 3 PD Dr. A. Vogel S-H

Mechanisms of Photobiology and Photomedicine 3 Dr. H. Diddens S-I

Lighten up the dark: Modern fluorescence methods in structural biology

3 Prof. Dr. C. Hübner S-K

Computational methods for lead identification and optimization 3 Prof. Dr. H. Steuber S-L

Strategies of Antiviral Drug Discovery 3 Prof. Dr. R. Hilgenfeld S-M

Isolation, synthesis and characterisation of natural products 3 Prof. Dr. K. Seeger S-N


33

Module Optional Programme

Topic: See Optional Programme overview (each student may choose 2 courses)

Semester: 3rd Semester


Instructors: See overview Optional Programme


Part of the Curriculum: MLS / Master / Optional Subject


Lecture / seminar or practical course / total 4 WH (each course 2 WH)

Workload: Total 60 h presence and 120 h private study

ECTS-Points: 6

Prerequisites: BSc in Molecular Life Science or related fields. Passed all modules of the 1. Semester

Goals: 1. Improving the knowledge in special parts of Cell- and Structural Biology and its application in Medical and Biomedical Technologies

2. To provide an insight into actual research projects

3. Working with technical literature

Content: Refer to Optional Programme overview

Type of examination: Refer to Optional Programme overview; the marks of two passed topics are valued 50% for each topic.

Literature: Textbooks, scientific articles, see separate courses


34

Optional Programme Cell biology

Module: Optional Programme Cell biology

Topic: Neurogenetics: Mutations, pathology and diseases



Instructors: Prof. Dr. C. Klein (Klinik für Neurologie)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: Understanding of mutations and resulting diseases, selected ex-amples

Content: 1. Study of relevant literature

2. Presentation of scientific results

3. Correlation mutation to function

4. Selected topics: Huntington´s disease, fragile X syndrome, Parkinson´s disease

Type of examination: Presentation

Literature: Selected scientific articles


35


Topic: Intracellular membrane traffic – molecular mechanisms and approaches



Instructors: Prof. Dr. R. Duden (Institute of Biology)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: 1. Survey of membrane traffic pathways

2. Discussion of experimental approaches used in the field

Content: 1. Membrane-bound organelles

2. Vesicle mediated protein traffic

3. Transport pathways

4. Model systems and assays

5. Live cell microscopy

Type of examination: Oral presentation, discussion of original research papers

Literature: To be announced at start of course


36


Topic: Intracellular Topogenesis of Proteins - Concepts and Experi-mental Methods



Instructors: PD. Dr. K.-U. Kalies (Institute of Biology)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: 1. Improving the knowledge about the protein transport into the endoplasmic reticulum (ER)

2. Developing skills in the design of experiments and the use of model organisms, using examples of intracellular protein transport

Content: 1. Starting point is the signal hypothesis of Blobel and Dobberstein

2. Milestones and errors as well as misinterpretations in the field of protein transport into the ER of the last 30 years are discussed in detail using original papers

3. Focusing on methods used (eg. translocation assays, ribosome binding assays, chemical and photochemical cross-linking, fluorescence quenching, reconstitution of proteoliposomes, EM, cryo-EM, crystal structure of protein translocation channels, electrophysiology)

4. Analyzing the design of the used experiments and critical interpretation of results

Type of examination: Final discussion with rating

Literature: Original papers will be distributed at the first appointment


37


Topic: Experimental Immunology



Instructors: Prof. Dr. C. Hölscher (Immunchemie und medizinische Mikrobiolo-gie, FZB)

Language: German



Lecture with student talk – discussion - / 2 WH


ECTS-Points: 3



Goals: 1. Immunological topics should be discussed on the basis of ex-perimental examples.

2. Relevant scientific publications should be comprehended in an accompanying seminar.

Content: 1. Animal models

2. Organisation and function of the immune system

3. Pathogens

4. The unspecific immune system

5. B lymphocytes and antibodies

6. T cells

7. Effector mechanims against infectious agents

8. Inflammation

9. Allergy

10. Tumour immunology

11. Tolerance and autoimmunity

12. Immun defects

13. Vaccination

14. Ethics in animal experiments

15. Biometric design and statistical evaluation of immunological experiments

Type of examination: Attendance and presentation

Literature: Immunobiology: The Immune System in Health and Disease; Char-les A. Janeway, Paul Travers, Mark Walport, Garland Science Publishing, 6th edition, 2005, ISBN 0815341016


38


Topic: Functional anatomy of lymphatic Organs



Instructors: Dr. K. Kalies (Institut für Anatomie)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: 1. Consolidation of the knowledge (of the structure and function of lymphoid organs) – lymphoid organs´ structure and function

2. Critical analysis of original research articles in small groups

3. Overview of the mechanisms that underlie the pathogenesis of genetically determined primary human immunodeficiencies

Content: Function and structure of lymphoid organs

1. Thymus

2. Lymph node

3. Extracellular matrix

4. Spleen

5. Germinal center

Type of examination: Oral presentation of reviews and original research articles, a writ-ten summary of the main topics on 2 pages

Literature: Reviews, scientific articles


39


Topic: Regulation of Gene Expression



Instructors: PD Dr. C. Zechel (Klinik für Neurochirurgie)




Seminar / Exercise / 1 week en blocque


ECTS-Points: 3



Goals: 1. Knowledge of the different levels of gene regulation and the DNA-elements required for basal and regulated transcription: (i) core promoter, (ii) enhancer, silencer, bi-functional elements, (iii) transcription by RNA polymerases I, II and III (processes and protein complexes)

2. Knowledge of the role of the chromatin structure in gene regulation: (i) Chromatin, (ii) histones, (iii) regulatory relevant histone modifications, (iv) „histone-code“, (v) chromatin condensation and de-condensation (processes and protein complexes), (vi) related ontogenetic aspects

3. Knowledge of processes resulting in permanent repression of chromatin and overview about the proteins involved: (i) SWI/SNF, (ii) HAT, (iii) HDAC, (iv) NURD, (v) CoR, (vi) related ontogenetic aspects

4. Knowledge of the role of RNA-species for the regulation of gene expression (processes and types of RNA-species)

5. Overview of regulation principles used by different cell types and transcription factors: (i) e.g. agonists or antagonists, phosphorylation, limited and specific proteolyses; (ii) gene regulation in the context of development, homeostasis and tumors; (iii) mechanisms that regulate the activity of transcription factors such as AP1, p53, NFΚ, nuclear receptors, bHLH-family, Hox-family, Notch

Content: 1. Theoretical part (Seminar on topics A - E)

2. Hands on course (transcriptional analyses)

Type of examination: Seminar: Oral presentation (20 minutes plus 10 minutes of discus-sion); hands on course: Protocol consisting of sections aim, result, and conclusion.

Literature: Lodish et al. Textbook Molecular Cell Biology

Alberts et al. Textbook Molecular Biology of the Cell

Original papers and reviews


40


Topic: Neural Differentiation of Progenitor Cells



Instructors: PD Dr. C. Zechel (Klinik für Neurochirurgie)




Seminar / Exercise / 1 week en blocque


ECTS-Points: 3



Goals: 1. Knowledge of the specific features of stem cells: (i) stemness and self renewal, (ii) stem cell niche (iii) importance of the cell division plane, (iv) cell fate decision, (iv) plasticity

2. Knowledge of the processes that regulate neural differentiation in vivo: (i) embryonal stem cells, (ii) fetal stem cells, (iii) adult neural stem cells and progenitors, (iv) „neural crest“ cells.

3. Overview on protocols that allow for neural differentiation in vitro: (i) embryonal stem cells, (ii) fetal stem cells, (iii) adult neural stem cells and progenitors, (iv) non-neural adult stem cells.

4. Basic knowledge of neurogenesis and the process of lateral inhibition.

5. Overview of the role of the top key regulators of neural differentiation and understanding of the underlying cellular and molecular mechanisms.

Content: 1. Theoretical part (Seminar on topics A - E)

2. Hands on course (neural differentiation)

Type of examination: Seminar: Oral presentation (20 minutes plus 10 minutes of discus-sion); hands on course: Protocol consisting of sections aim, result, and conclusion.

Literature: Lodish et al. Textbook Molecular Cell Biology

Alberts et al. Textbook Molecular Biology of the Cell

Original papers and reviews


41


Topic: Characterisation and relevance of DNA-repair for tumour de-velopment



Instructors: Prof. Dr. H.-W. Stürzbecher (Institut für Pathologie)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: 1. Principles of tumour development

2. DNA-damage - repair-mutations

3. Chromatin disorganisation in tumour development: principles of dysregulation of epigenetic mechanisms in tumour develop-ment

Content: 1. Tumour development

1.1 Genetic models in carcinogenesis

1.2 Cytokines and receptors

1.3 Signal transduction

1.4 Tumour selection and differentiation

2. DNA-damage -repair- mutations

2.1 Types of mutations and reasons for

2.2 Repair pathways

2.3 Genetic control of mutation rate

2.4 Inherited defects in human repair systems

2.5 Regulatory response to DNA damage

2.5.1 cell cycle arrest and DNA-repair

3. Chromatin dys-organisation in tumour development

3.1 Modifications of the chromatin-architecture: DNA-methylation - the histone-code - Chromatin-remodelling

3.2 Defect DNA-repair: Causes and consequences

3.3 Modulation of gene expression

3.4 Global changes of the chromatin-structure and Pathology


Literature: Textbooks, scientific articles


42


Topic: Validation and quantification of miRNAs in malignant lym-phomas



Instructors: Prof. Dr. H.-W. Stürzbecher (Institut für Pathologie)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: 1. miRNA biogenesis machinery

2. Reasons for abnormal miRNA expression

3. Relevance of abnormal miRNA expression in tumours

4. miRNA applications

Content: 1. miRNA biogenesis machinery

1.1 Processing of primary miRNA by Drosha/DGCR

1.2 Charging of mature miRNA to the RISC complex

1.3 Mechanisms of translational inhibition by miRNA

2. Reasons for abnormal miRNA expression

2.1 Chromosomal abnormalities

2.2 Epigenetic changes

2.3 Mutations and SNPs

2.4 Defects in the miRNA biogenesis machinery

3. Relevance of abnormal miRNA expression in tumours

3.1 Oncogenes

3.2 Cell cycle regulation

3.3 Progression and metastasis formation

4. miRNA applications

4.1 miRNA as diagnostic and prognostic tool

4.2 miRNA as therapeutic tool


Literature: Textbooks, scientific articles


43

Optional Programme Structure Biology

Module: Optional Programme Structure Biology

Topic: Mass Spectrometry of Biomolecules



Instructors: PD Dr. B. Lindner (LG Immunchemie, FZB)

Prof. Dr. U. Zähringer (LG Immunchemie, FZB)

Language: German or English



Lectures / 1 WH

Exercise / 1 WH


ECTS-Points: 3



Goals: 1. Understanding physical and und chemical basics of MS-instrumentation

2. Survey on the fields of application in biosciences

3. Getting insight into experimental practise

Content: Lectures / Seminars:

1. Fundamentals of MS analysers: Quadrupole mass filter, Ion-Traps, TOF-MS, FT-MS, MS/MS techniques

2. Characteristics of ion sources: EI, MALDI, ESI

3. Coupling MS and chromatographic methods: GLC, HPLC, CE

4. Interpretation of MS-Data: Component-Analysis with GLC-EI-MS, Identification of proteins and lipids (proteomics, lipidomics), MS/MS analyses of peptides and oligosaccharides

Exercises:

Application-oriented experiments to consolidate the knowledge presented in the lectures

Type of examination: Regular attendance, oral presentation of reviews and of the results of the own experiments.

Literature: Mass Spectrometry: Principles and Applications: Edmon de Hoff-mann, and Vincent Strobant, John Wiley & Sons LTD, Eng-land, 2002, ISBN 0-471-48566-7

Scientific papers


44


Topic: Special Topics of Biochemistry: Lipids, Glycolipids and struc-ture-related membrane components, Oligo-, Polysaccharids and Glycoproteins



Instructors: Prof. Dr. U. Zähringer, (LG Immunchemie, FZB, 1. Part)

Prof. Dr. O. Holst (LG Strukturbiochemie, FZB 2. Part)

Language: German



Lecture / 2 WH


ECTS-Points: 3



Goals: 1. Understanding the structure-function ratio of biologically and biomedically important molecules

2. Understanding problems of modern bioinformatics

3. Knowledge of structures of molecules

Content: Part 1 Glycolipids, lipoproteins, membrane components:

1. Introduction

2. Structure, occurrence and properties

3. Synthesis, biosynthesis and decomposition

3.1 Chemical syntheses, strategies of syntheses, carrier syn-theses, labeling experiments.

3.2 Biosynthesis of lipoconjugates, transport mechanisms

3.3 Degradation, turnover in eucaryotic cells: plants, fungi, mammalian cells

4. Structural analysis of lipids and lipoconjugates

4.1 Synthesis and purification: Analytical and preparative chromatography

4.2 NMR Spectroscopy, aggregates

4.4 Serological and biological analysis of lipoconjugates

5. Application and impact of lipoconjugates in bio-medicine: function

5.1 Membranes

5.2 Carrier (synthetic and natural)

5.3 Synthetic and semi-synthetic lipids

5.4 Cellkompartments

5.5 Immunology of lipoconjugates


45

5.6 Cell-biological impact of lipoconjugates

5.7 Pharmakological impact

6. Lipoconjugates in Immunology

6.1 As carrier of information in innate Immunity

6.2 As carrier of information in adaptive Immunity

7. Pathobiochemistry of lipids (functional disorders)

7.1 Metabolic diseases

7.2 Lipoconjugates in tumors and cancer

7.3 Labelling experiments in pathobiochemistry

8. Signal transduction in membranes

Part 2 Oligo- and polysaccharides and glycoproteins:

1. Introduction

2. Structure, occurrence and properties

2.1 Polysaccharides of bacteria and fungi

2.2 Oligo- and polysaccharides of plants

2.3 Polysaccharides of animals

2.4 Peptidoglycan

2.5 Glycoproteins of viruses

2.6 Glycoproteins of bacteria and fungi

2.7 Glycoproteins of plants

2.8 Glycoprotein of animals

2.9 Glycopeptidantibiotics

3. Synthesis, biosynthesis and decomposition

3.1 Biosynthesis of polysaccharides and glycoproteins, transport mechanisms

3.2 Chemical syntheses

3.3 Degradation of polysaccharides and glycoproteins

4. Structural analysis of polysaccharides and glycoproteins

4.1 Synthesis and purification: Analytical and preparative chromatography

4.2 NMR Spektroskopy

4.4 Serological and biological analyses

5. Function: Impact and application of polysaccharides and glycoproteins

5.1 Membranes and cell walls

5.2 Cell recognition

5.3 Mucins, heparin, blood groups

5.4 Immunology, vaccines, allergens

5.5 Antibiotics, drugs, probiotics

5.6 Food and non-food products, agro fibers


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6. Pathobiochemistry

6.1 Metabolic diseases

6.2 Tumors and cancer


Literature: Part 1 Glycolipids, lipoproteins, membrane components:

Bioanalytik:F. Lottspeich und H. Zorbas (Hrsg.). Spektrum, Akademischer Verlag, Heidelberg, Berlin, 1. Auflage 1998

Part 2 Oligo- and polysaccharides and glycoproteins:

Kohlenhydrate: Chemie und Biologie: Lehmann, Jochen Wiley-VCH, 1996, ISBN 3-527-30859-8


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Topic: Biochemistry of Transition metals



Instructors: Prof. Dr. B. Matzanke-Markstein (Isotopenlabor)




Seminar / 2 WH


ECTS-Points: 3



Goals: 1. Comprehending the role of heavy metals in processes of biochemical importance

2. Application of the knowledge acquired in other modules on metalloproteins (analysis of protein structure, spectroscopies and additional biochemical methods)

Content: 1. Properties of heavy metals of biochemical relevance.

2. Structure and function of metalloproteins

3. Incorporation, trafficking, homeostasis and detoxification of metals in biological systems.


Literature: Bioanorganische Chemie. Zur Funktion chemischer Elemente in Lebensprozessen. W. Kaim, B. Schwederski, Teubner Verlag, Stuttgart, 3. Auflage

Metal Sites in Proteins and Models - Redox Centers; H.A.O. Hill, P.J. Sadler, A.J. Thompson (Eds.) Springer Verlag 1999


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Topic: NMR and drug design



Instructors: Prof. Dr. T. Peters, Dr. H. Peters, PD Dr. T. Weimar (all scientific research-members of the Institute of Chemistry)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: 1. Acquisition of in-depth knowledge of NMR experiments which identify and characterize protein-ligand interactions

2. Acquiring knowledge of the use of NMR active isotope labels

3. Learning criteria when and where to apply NMR in the drug design process

Content: 1. Basics

1.1 Chemical exchange and NMR time scales

1.2 Thermodynamic and kinetic aspects of protein-ligand binding

2. Ligand based techniques

2.1 Transfer NOE

2.2 Saturation transfer (STD NMR, Water-LOGSY)

2.3 Longitudinal and transverse relaxation times

2.4 Diffusion constants

3. Protein based techniques

3.1 HSQC techniques

3.2 Saturation transfer techniques

4. Expression and purification of istope labeled proteins

4.1 Uniform isotope labeling (15-N, 13-C, 2-H)

4.2 Amino acid selective isotope labeling (15-N, 13-C, 2-H)

4.3 Deuteration

5. Examples for the use of NMR in drug design

5.1 Entry inhibitors against human rhinoviruses

5.2 Protease inhibitors against Hepatitis C

5.3 Glycosyltransferase inhibitors and their potential in cancer therapy

Type of examination: Oral colloquium

Literature: Current research literature


49


Topic: Molecular Dynamics



Instructors: PD Dr. H. Paulsen, Institut für Physik (www.physik.uni-luebeck.de)

Language: German (English by request)



Lecture / 2 WH


ECTS-Points: 3



Goals: 1. Fundamentals of molecular dynamics

2. Applications of molecular dynamics to biomolecules

Content: 1. Energy minimization and discrete Newtonian dynamics (Verlet algorithm)

2. Force fields: stretching, bending, torsion, fields of application (proteins, DNA, universal)

3. Treatment of Coulomb and van der Waals interactions (cutoffs, Ewald summation)

4. Influence of temperature and pressure: thermostats and barostats

5. Hybrid methods: classical force fields combined with quantum mechanical treatment

6. Examples using gromacs (www.gromacs.org)

Type of examination: Written examination or contributed presentations

Literature: A. Leach: Molecular modelling

http://lccn.loc.gov/00046480


50


Topic: Nucleic acid drugs



Instructors: Prof. Dr. G. Sczakiel (Institut für Molekulare Medizin)

Language: German



Seminar / 2 WH


ECTS-Points: 3



Goals: 1.Insights into current research on nucleic acid based drugs

2.Insights into the mode of action of nucleic acid based drugs

3. Analysing relevant publications and introduction to a colloquium with discussion

4.Capability to analyse publication in this fields

Content: 1. Design and validation of nucleic acid-based tools and drugs (aptamers, antisense, siRNA and miRNA)

2. Nucleic acid delivery

3. Pharmacology & toxicology

4. Animal models

5. Clinical studies in phases I, II and III

6. Final stages of drug development

Type of examination: Discussion with the mentor and oral presentation

Literature: Handbuch der Molekularen Medizin, Bd.1 : Molekularbiologische und Zellbiologische Grundlagen von Detlev Ganten, Klaus Ruck-paul, Springer, Berlin , Oktober 2002, ISBN: 3540432078

Antisense Drug Technology von Stanley T. Crooke, Language: English, 916 Seiten - Marcel Dekker , September 2001, ISBN: 0824705661

Current research and review articles


51


Topic: Structural Aspects of Protein biosynthesis



Instructors: Dr. J. R. Mesters (Institut für Biochemie)

Language: English



Seminar / 2 WH


ECTS-Points: 3



Goals: 1. Expanding basic knowledge of the protein-biosynthesis process

2. Expanding basic knowledge in structural biology

3. Handling of scientific literature


5. To rank and discuss scientific results

6. Apply acquired knowledge from other fields to structural biology

Content: 1. Seminar series

2. Analysis of the most recent and relevant scientific publications and presentation thereof followed by a discussion

Type of examination: Presentation followed by a discussion and defence

Literature: Structural Aspects of Protein Synthesis; Anders Liljas, World Sci-entific Publishing, London Singapore, ISBN 981-238-867-2


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Topic: Modern Optical Techniques in Biomedicine and Biotechnology



Instructors: Prof. Dr. A. Vogel (Institut für biomedizinische Optik) et al

Language: German



Lecture / 1 WH (compact course within one week)

Practical course / 1 WH (compact course within one week)


ECTS-Points: 3



Goals: 1. Basic knowledge of modern optical techniques in Biomedicine and Biotechnology

2. Practical experience in applying those techniques to problems in Biomedicine and Biotechnology

Content: Lecture:

1. Basic concepts of quantum optics, wave optics, geometrical optics. Microscopic imaging in geometric optical and Fourier optical description

2. Coherent filtering, phase contrast and differential interference contrast imaging (DIC)

3. Modern light sources (lasers, white light sources, LEDs)

4. Basics of spectroscopy (absorption, fluorescence, FRET)

5. Confocal laser scanning microscopy

6. Nonlinear microscopy (multiphoton excitation, 2nd harmonic)

7. Flow-cytometry, (fluorescence-activated cell sorting, FACS)

8. DNA- and protein chips

9. Tissue optics, Interaction of light with cells and tissues

10. Optical manipulation of cells (laser tweezers, microdissection, laser-catapulting, nanoparticle-cell surgery, CALI)

Practical course:

1. Coherence, interference, diffraction, Fourier optics

2. Microscopic illumination, imaging, and resolution

3. Coherent filtering, phase contrast, DIC

4. Fluorescence spectroscopy

5. Confocal laser scanning microscopy

6. Nonlinear microscopy via multiphoton excitation and 2nd har-monic generation


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7. FACS

8. Laser microdissection, laser-catapulting, and cell surgery

Type of examination: Marked protocols

Literature: Textbooks, scientific papers


54


Topic: Mechanisms in Photobiology and Photomedicine



Instructors: Dr. rer. nat. Heyke Diddens (Institut für Biomedizinische Optik)

Language: German


Teaching method / atten-dance requirements

Lecture / Seminar / Practical course /2 WH (1 week en blocque)

Workload: 30 h presence und 60 h private study

ECTS-Points: 3



Goals: 1. Understanding basic mechanisms underlying photochemically induced biological processes

2. Basic knowledge of possible fields of application of photochemical reactions in biology and medicine

3. Practical experience in the field of experimental photodynamic therapy

Content: 1. Fundamentals of photochemical processes

2. Basic principles of photochemically induced biological reactions

3. Chromophor-enhanced selective photothermotherapy

4. Application of photochemical reactions in fundamental research in biology

5. Application of photochemical reactions in medicine-like fluorescence diagnosis, phototherapy, photochemotherapy and photodynamic therapy

6. Experiments on antimicrobial photodynamic therapy


Literature: Scientific papers


55


Topic: Lighten up the dark: Modern fluorescence methods in struc-tural biology



Instructors: Prof. Dr. C. Hübner




Lecture / 1 WH

Seminar / 1 WH)


ECTS-Points: 3



Goals: 1. Knowledge of modern methods of fluorescence

2. Confidence in literature management


4. Assessment of scientific results

Content: 1. Basics in fluorescence

2. Photo physics

3. Energy transfer

4. Single molecule fluorescence

5. Fluorescence correlation spectroscopy

Type of examination: Regular attendance, oral presentation

Literature: Recent publications


56


Topic: Computational methods for lead identification and optimization



Instructors: Prof. Dr. H. Steuber (Institut für Biochemie)




Lecture / 2 WH


ECTS-Points: 3



Goals: 1. Basics and current limitations of molecular modelling

2. Knowledge about the method repertoire for lead identification, optimization and affinity estimation

Content: 1. Virtual “synthesis” of small molecules in silicio

2. force fields and minimization techniques

3. types of interactions between atoms and molecules

4. techniques of charge calculation

5. basics of molecular docking/virtual screening

6. field-based methods for ligand optimization

7. molecular dynamics simulations of macromolecules and protein-ligand complexes

8. theory and experimental basics of the thermodynamics of protein-ligand interactions

Type of examination: Regular attendance, oral presentation

Literature: Recent publications


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Module: Optional Programme Structural Biology

Topic: Strategies of Antiviral Drug Discovery



Instructors: Prof. Dr. R. Hilgenfeld (Institut für Biochemie)

Language: English



Lecture / 2 WH


ECTS-Points: 3


Passing the virology module of the 1st semester

Goals: 1. Understanding fundamental strategies in antiviral drug discovery

2. Obtaining knowledge of selected methods in antiviral drug design

Content: Topics of the module deal with interfering with the following processes/target molecules that are essential in viral infections:

1. Fusion/Entry

2. Reverse Transcriptase

3. Integrase

3. Polymerase/Helicase

4. Viral Proteases

5. Neuraminidase

6. mRNA

7. Host Factors

For each topic, 1 - 2 literature seminars (20-25 min, maximum 30 min) on selected specialized subtopics will be givev by participants

Specialized subtopics comprise interesting inhibitor design, methodology, chemical synthesis, target peculiarities.

Type of examination: None

Literature: e.g.: Manns, M.P., Foster, G.R., Rockstroh, J.K., Zeuzem, S., Zoulim, F. and Houghton, M. (2007) Nat Rev Drug Discov.6, 991-1000


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Module: Optional Programme Structural Biology

Topic: Isolation, synthesis and characterisation of natural products



Instructors: Prof. Dr. K. Seeger (Institute of Chemistry)

Language: German



Lecture / Seminar / Practical course /2 WH (course block)


ECTS-Points: 3



Goals: 1. Planning and execution of Synthesis’ and handling of different hazardous materials

2. DFeeper understanding of chemical reactions and substances

Content: 1. Functional groups in natural products and their reactions

2. Isolation and synthesis of natural products

3. Structure elucidation of natural products

Type of examination: Marked protocols

Literature: Peter Nuhn, Naturstoffchemie: Mikrobielle, pflanzliche und ti-erische Naturstoffe; Hirzel, S; Auflage: 4.

K. C. Nicolaou und Tamsyn Montagnon, Molecules that changed the World: A Brief History of the Art and Science of Synthesis and its Impact Society Wiley-VCH; Auflage: 1

Stefan Berger und Dieter Sicker, Classics in Spectroscopy: Isola-tion and Structure Elucidation of Natural Products, Wiley-VCH; Auflage: 1

Scientific papers


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Master Thesis

Module: Master Thesis

Topic: Master Thesis

Semester: 4th Semester

Responsible instructor: “Prüfungsausschussvorsitzender”

Instructors: All of our program´s lecturers licensed to take an exam.

If the Master thesis is done externally (outside our university) the student has to choose a licensed lecturer (see PO) of our univer-sity as a second instructor who will be First Examiner in the exami-nation.




Self-dependent practical work / 6 months

Workload: 900 h presence

ECTS-Points: 30

Prerequisites: Minimum of 82 ECTS

Goals: 1. The project should show that the student is able to do his own scientific research in a defined time with little help by the instructor, write and present a thesis on the chosen topic and defend it.

2. Training in independent scientific work

Content: Scientific project in the field of molecular life sciences

Type of examination: Written thesis with presentation and defence

Literature: Is recommended by the lecturer

Molecular Life Science

Technology

Transcript of Molecular Life Science