The MSc course lasts for 4 semesters (2 years), starting at the beginning of October each year. With careful planning, it can also be completed in 18 months.
In the first Semester, you will attend a lecture course that is provided for all MSc students in biological sciences, and also participate in two advanced practical courses. The second semester starts with a module that concentrates on techniques; in addition to lectures, you choose three one-week practicals from a wide range of options. The fourth module offers the opportunity to learn about the research going on within MCB, and to practice writing a research proposal; at the same time you will undertake a 6-week project in a laboratory of your choice. Two further, 8-week laboratory practicals will enable you to widen your experience and choose the lab in which you would like to complete your 6-month master thesis. Throughout the course, you will participate in literature and research seminars in which you can learn to critically assess research papers and improve your language and presentation skills.
This semester consists of two modules, which provide a solid background in advanced molecular biosciences. Each module lasts 9 weeks, of which 6-7 weeks are spent in course work and 2-3 weeks are allowed for exam preparation.
The formal course work for each module consists of:
Lectures which provide theoretical information, with accompanying Tutorials. The lectures are attended by all students of the MSc course. There are written examinations at the end of each.
Practicals: 3 weeks, all day, taught courses. Each practical also has an accompanying literature seminar in which important research papers relevant to the course are presented and critically discussed by the students. The seminars also focus on improving your language and presentation skills.
Module 1 (October-December) - choice between
a) Studies of vesicular transport, using in vitro systems and using yeast genetics
b) Protein targeting to mitochondria, ribosome biogenesis, and vesicular transport - using in vitro systems, yeast and Neuropsora
c) Gene expression: Chromatin modifications, mRNA transport, decay and translation, in mammalian cells and trypanosomes
Module 2 (December -February) - choice between
a) Protein folding: includes various biophysical methods such as spectroscopy and mass spectrometry.
b) Antibodies: everything you need in order to use them
c) Quantitative biology.
For more details, please just scroll down on this page.
Module 3 (April-June)
The lecture course is on advanced methods, such as mass spectrometry, NMR, enzymes, protein folding and networks, crystallography, yeast and Drosophila genetics, advanced microscopy, and computer simulation. We aim to ensure that you are aware of the capabilities and limitations of most important methods, so that you not only choose suitable approaches for your own work, but also critically assess the primary literature.
You choose three practicals from a list that includes:
Enzyme Kinetics and Protein Folding
Quantitative analysis of sumoylation with a FRET-based enzyme assay
Quantitative Protein analytics
Functional Analysis of Protein-Lipid Interactions
Fluorescence Microscopy of Living Objects
Biomolecular modelling and simulation methods
PERL for beginners
Components and Mechanisms of Signal Transduction (shared with Cancer Biology)
Carbohydrates in plants
The numbers of students taking part range from two to 12, depending on capacity and the availability of instruments. Some of the practicals are "samplers" that are run in the research laboratories of the organisers. For more details, please just scroll down on this page.
Two or three literature seminars are offered separately from the practical. These change from time to time - in 2015 they are on drug development and organelle dynamics.
Module 4 (March and June-August)
In the lectures, the staff of MCB - including many who you may not have met before - introduce their research to you. These lectures take place over 3 weeks in February-early March, so you can hear them in advance of choosing lab practicals. Attendance is obligatory.
Instead of having a formal examination on the lectures, you choose a topic proposed by one staff member in order to write an MSc thesis research proposal. This can be done in the summer.
You also do a six-week practical in a lab of your choice, and attend the literature and research seminars of that group. This is formally scheduled after module 3, but if you want to finish the course fast you can instead do it in February-April after the lectures.
Module 5 (October-December)
This is an 8-week practical in the lab of an MCB staff member, with attendance of lab seminars.
Module 6 (December - February)
This is like Module 5, except that you can do it in any lab, anywhere, that is approved by the course coordinator. If you are outside Heidelberg you can also choose to stay for longer than 8 weeks, but only 8 weeks' work is graded.
Masters thesis (February-July, 6 months)
For the Masters thesis you can choose any of the MCB staff as a supervisor. The experimental work is done in the supervisor's laboratory, in Heidelberg.
If you do the module 4 lab practical you can finish modules 5 & 6 over the summer, start your MSc thesis work in October, and complete the MSc in 18 months.
FURTHER DETAILS OF PRACTICALS
Course title: Cell free systems and genetic strategies to analyse protein targeting, quality control and degradation
Lecturer: M. Lemberg, S. Schuck
Course Content: The aim of the practical is to investigate the fate of secretory and membrane proteins in the Endoplasmic Reticulum (ER) using different experimental systems. You will learn how to develop and set-up a cell-free (in vitro) translation/translocation system. With such a system reconstituted from isolated components, you will then study the translocation process of different types of secreted and membrane-spanning proteins. This work will include the preparation of in vitro transcribed mRNA and assays for protein translocation and studies addressing the topology of transmembrane proteins. In the second part, we will investigate mechanisms of protein quality control and degradation. If newly translocated proteins are unable to fold properly, they are destroyed by ER-associated degradation (ERAD), which we will analyse in mammalian tissue culture cells using cycloheximide chase experiments. Alternatively, cells can dispose of damaged organelles along with misfolded or aggregated proteins by autophagy, a process we will investigate in the model organism Saccharomyces cerevisiae. You will biochemically follow autophagy of ER. Finally, you will learn how genetic screens in yeast can be harnessed to identify proteins important for maintaining ER function.
Course title: Biochemistry of cell organelles
Lecturers: E. Hurt, F. Wieland, M. Brunner
Course Content: The objective of the course is the acquisition of knowledge of modern biochemical methods, which the participants must then apply to the solution of problems in the field of cell organelles. Throughout the semester, students give oral presentations on subjects discussed in the course bibliography, with the double purpose of perfecting their oral skills and acquiring the necessary background knowledge. The relevant themes are divided into three groups: 1 Reconstruction of the intercellular vesicular transport 1.1 Subcellular fractioning of liver homogenates for the enrichment/enhancement of Golgi membranes 1.2 Recruiting of cytosolian COPI-cyst components at/to Golgi membranes 2 Nuclear transport and ribosome biogenesis 2.1 Protein transport through nuclear pores 2.2 mRNA biogenesis 2.3 Ribosome biogenesis 3 Mitochondria: structure and function 3.1 Protein import in mitochondria 3.2 TIM/TOM complex Applied techniques: E. coli and S. cerevisiae lysis, affinity purification with TAP and GST tags, SDS-PAGE, in vitro binding studies, differential centrifugation, immunoprecipitation, western blotting, protein determination, in vitro membrane binding experiments, cultivation of N. crassa, isolation of mitochondria from N. crassa and S. cerevisiae, in vitro transcription and translation of a chimeric protein, protein import in isolated mitochondria. Duration: 3 weeks, full day + seminar
Course title: Gene expression
Lecturers: C. Clayton, R. Voit, G. Stoecklin
Course Content: In this practical we study various aspects of gene expression. The first week is devoted to epigenetics in mammalian cells, while the second two weeks are spent characterising RNA in both animal cells and trypanosomes. Students will learn chromatin immunoprecipitation, Northern blotting, and in situ hybridisation, study mRNA polyadenylation and degradation, and use RNA interference to study export of mRNAs from the nucleus. Success in the course is judged by written reports and answers to questions, as well as adequate lab book maintenance and performance in the lab. In the accompanying seminar students will analyse recent publications covering a broad variety of functions of RNA. The grade is based on an oral ad projected presentation and on participation in discussions.
Course title: Biochemistry of the cell: molecular methods to study protein folding and protein interactions
Lecturers: B. Bukau, A. Mogk, M. Mayer
Course Content: The objective of this course is to provide you with an introduction to the complex problematic of protein folding and degradation in the cell. You will work with different key chaperones and a protease, which mediate protein folding, disaggregation and degradation. During this course you will learn different methods to probe protein folding and degradation in vitro and in vivo. In addition you will gain hands on experience in basic methods of protein purification and characterization. You will learn fundamental biochemical and biophysical methods like ATPase assays, basic CD and fluorescence spectrometry, one and two dimensional gel electrophoreses, western blotting and MALDI mass spectrometry, which are of great use in characterizing proteins and enzymatic activity in all areas of biochemical and biophysical research. Duration: 3 weeks, full day + seminar
Course title: Antibodies - essential tools in molecular cell biology. Recapitulate the discovery of sumoylation.
Lecturers: F. Melchior and lab members
Course Content: Antibodies are extremely valuable tools in all aspects of molecular cell biology. They serve to investigate protein expression and localization in cells, allow identification of binding partners and of posttranslational modifications, and can be used as inhibitors in the analysis of intracellular processes. The aim of the practical is to develop an appreciation for the power of high quality antibodies in molecular cell biology. After purifying recombinant untagged RanGAP1 from bacteria (involving refolding, anion exchange chromatography and gel filtration), you will affinity purify polyclonal anti RanGAP1 antibodies from serum and use them in immunoblotting, immunoprecipitation and immunofluorescence studies (requires cultivation of HeLa cells and preparation of diverse HeLa lysates). With these experiments you will recapitulate some key experiments in the discovery that RanGAP1 is posttranslationally modified with SUMO1. Upon site directed mutagenesis of an HA epitope tagged RanGAP1, you will compare wt and sumoylation deficient RanGAP1 localisation by immunofluorescence analysis with monoclonal anti HA antibodies in transfected HeLa cells. Seminars given by the instructors will cover antibody production, purification and applications. Literature seminars given by the students will be based on original articles that demonstrate application of antibodies in nucleocytoplasmic transport and mitosis (Ran GTPase cycle) and in the field of posttranslational modifications (sumoylation, ubiquitylation and phosphorylation).
Course title: Quantitative Biology
Lecturers: Michael Knop, E. Schiebel, Gislene Pereira
Quantitative Biology denotes the application of theoretical models in concert with experimental work to analyze the functioning of biological systems. Thereby, the experimental designs needs to be quantitative to provide data suitable for modelling and theoretical or computational analysis.
To this end this course aims at learning those skills in applications to model biological problems using a variety of quantitative biological methods, with a focus on microscopy and on different cell systems, yeast or tissue culture. As paradigmatic examples in the course fluorescent protein technology will be taught and further developed to teach students a solid base for the associated range of applications of this important technology in their future careers.
“Quantitative tools are the microscope of the future - learn them now!”
You will focus on the following topics:
1. Evolution of fluorescent proteins and screening using yeast as a model system.
2. Screening of a range of fluorescent proteins for brightness and maturation kinetics using flow cytometry and fluorescent plate readers.
3. Analysis of the tumour suppressor p53 in human cells using a tandem fluorescent reporter.
Discussed methods include:
1. Construction of stable human cell lines
2. In vivo cloning in yeast
3. Construction of genetically modified yeasts
4. Quantitative live cell imaging
5. Image segmentation and analysis
6. Computational data analysis using models
8. Fluorescent plate reader methods
9. Spectral analysis of probes
Duration: 3 weeks
Virus Capsid assembly - Lecturers: J. Reinstein
Course Content: Native Virus Particle isolation and in vitro Capsid assembly – purification, quality control and spectroscopic properties.
Max 4 Students
Particles of the mavirus virophage, a protist-infecting dsDNA virus, will be purified by Cesium chloride density gradient centrifugation. The resulting virus preparation will be analyzed for concentration and purity by qPCR, Nanosight nanoparticle tracking, and electron microscopy (EM).
The same virus capsid will be assembled in vitro from purified capsid proteins that were expressed recombinantly. They will be characterized with spectroscopic methods like dynamic and static light scattering (DLS, MALS), Fluorescence and also EM.
Structural Biology - Lecturers: I. Sinning, I. Schlichting
Course Content: Structural information on substrate specificity, and transition state geometry are important ingredients for deriving enzymatic reaction mechanisms and understanding protein function. The course will introduce methods used to characterize protein-ligand interactions in the crystalline state. Experimental approaches include crystallographic ones like soaking, microspectroscopy and mass spectroscopy of crystals followed by diffraction data collection, structure determination and interpretation.
Mass spectrometry - Lecturers: M. Mayer, T. Ruppert
Course Content: Aim of the course: Hands-on experience with different mass spectrometers, state of the art techniques in protein analytics and proteomics. MALDI-TOF, LC-ESI-QTOF and nanoLC-ESI-Orbitrap mass spectrometry is used to identify proteins out of 1D and 2D-SDS-gels, to analyze posttranslational modifications like phosphorylation, and to analyze protein conformation using amide hydrogen mass spectrometry.
Biochemistry and structure of RNA and protein-RNA complexes - Lecturers: J. Hennig, B. Simon, K. Wild
Run-off /in vitro /transcription of RNA using hammerhead-ribozyme technology; large scale purification of RNA; RNA folding requirements and strategies; introduction into RNA structure, RNA fold and function in computer practical with graphics software; NMR spectroscopy of RNA
and protein-RNA complexes. With accompanying seminars.
Protein simulation and modeling - Lecturer: S. Fischer
Course Content: Modern techniques in molecular modeling, simulation and graphics allow us to watch a single protein at atomic resolution, in real time and under physiological conditions - something that is not possible with experimental methods. This allows to truly understand the functional mechanism of a protein. The course explains these techniques, starting from the basics. Their application is illustrated on examples such as the molecular motor in muscle, the selectivity of trans-membrane channels and pumps, and the catalytic activity of enzymes. In the practical part, students start by downloading a protein from the Protein Data Bank of structures. The structure of this protein is then examined on workstations equipped with three-dimensional graphics, and computer simulations are performed. This includes watching the flexible deformation modes of the protein, observing its atomic motions with Molecular Dynamics, simulating an enzymatic reaction, and computing ligand binding properties. Given the interdisciplinary nature of the subject, the course is structured to address students with different scientific backgrounds. Duration: 1 week, full day
Quantitative analysis of sumoylation with a FRET-based enzyme assay - Lecturer: F. Melchior
Course Content: Posttranslational modification with ubiquitin related proteins of the SUMO family is an essential mechanism to regulate protein functions in eukaryotic cells. To study sumoylation in vitro, recombinant enzymes and substrates need to be generated with high purity. Analysis is conventionally done by SDS-PAGE and immunoblotting. We developed a FRET-based assay that allows rapid quantitative and time resolved analysis of many samples. FRET is a process by which the excited state energy of a fluorescent donor molecule is transferred to an acceptor molecule. Efficient energy transfer requires very close proximity, and can therefore be used as a read-out for covalent and non-covalent protein interactions. During the course, students will purify enzymes and substrates (this includes use of an Aekta chromatography system) and compare the efficiency of sumoylation using the conventional - and the FRET-based assay. Accompanying seminars will cover principles in protein purification, FRET and sumoylation.
Synthetic peptides - Lecturer: M. Cryle
The practical course will deal with the chemical synthesis of peptides focusing on:
- principles of solid phase synthesis of peptides (advantages and limitations in comparison to protein expression)
- strategies to synthesise C-terminal modified peptides
- Native Chemical Ligation (NCL)
As a model system putative intermediate peptides of the biosynthesis of vancomycin or teicoplanin biosynthesis will be used.
Analytical protein biochemistry - Lecturer: A. Winkler
In this practical course you will characterize three unknown protein samples by UV/Vis-spectroscopy, SDS-PAGE, mass spectrometry and other methods. This will enable you to identify these proteins and to analyze them in various levels of detail, providing you with the opportunity to assess the strengths and weaknesses of the various analytical methods.
Functional analysis of protein-lipid interactions using advanced methods in biochemistry and biophysics - Lecturer: B. Brügger
Preparation of liposomes differing in lipid composition and size:
Large unilamellar vesicles (LUVs, 200-300 nm)
Giant unilamellar vesicles (GUVs, 10-30 µm)
LUV binding assay: Fibroblast growth factor 2 (FGF2) and mutated FGF2 forms fused to green fluorescent protein (GFP) are incubated with LUVs. Binding efficiencies are analysed using flow cytometry (FACS) and quantified.
GUV assay: Binding of various FGF2-GFP constructs to GUVs. FGF2 membrane activity is monitored by penetration of a fluorescent tracer molecule (Alexa 488, green) into the GUV lumen. Analyses are done by confocal microscopy followed by statistical analysis.
Lipidomics of mammalian cells including lipid extraction, mass spectrometric analysis and data evaluation
Enrichment of proteins with covalent fatty acyl modifications by a click chemistry approach
Molecular mechanism in the formation of COPI vesicles- Lecturer: F. Adolf
The presence of an elaborate endomembrane system is a hallmark of eukaryotic cells. Intracellular transport between different organelles to maintain protein and lipid homeostasis is archived by vesicular transport. COPI-coated vesicles are transport carriers involved in the retrograde transport in the early secretory pathway between the ERGIC/Golgi compartments and the endoplasmic reticulum (ER), as well as in bidirectional transport between distinct Golgi cisternae.
Within the practical course different aspects of the life cycle of COPI-coated vesicles will be examined. This includes utilizing a variety of distinct in vitro reconstitution systems ranging from i) binding studies of purified COPI coat components (Arf1 and coatomer) and Arf GTPase activating proteins (ArfGAPs 1/2/3) to artificial liposomal membranes of defined sizes, to ii) the complete reconstitution of COPI-coated vesicles from semi-intact cells with purified coat proteins.
Bigay J, Antonny B. (2005) Real-time assays for the assembly-disassembly cycle of COP coats on liposomes of defined size. Methods Enzymol. 404:95-107.
Weimer C, Beck R, Eckert P, Reckmann I, Moelleken J, Brügger B, and Wieland FT. (2008) Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking.J. Cell Biol. 183(4):725-35.Adolf, F., Herrmann, A., Hellwig, A., Beck, R., Brugger, B., and Wieland, F.T. (2013). Scission of COPI and COPII Vesicles Is Independent of GTP Hydrolysis. Traffic 14, 922-932.
Information on Modules 4, 5 and 6
In Module 4 we offer lectures on many aspects of research that are going on within the MCB programme. These are informal, with opportunity for discussion, so we don’t have separate tutorials. They take place in February-March. Attendance is necessary for you to find out what is available, not only with regard to subjects, but also methods. Please sign the sheets provided. The lectures will take place from Feb 24th - March 6th 2015.
The examination takes the form of a Project proposal for a Masters thesis. Topics for these proposals will be given by the lecturers in Module 4. You can also ask other MCB teachers but not someone from outside MCB.
The proposal should be between 3500 and 4500 words long excluding the references.
Sections are: Abstract, Background, Experimental design and methods, References.
The supervisor will give you some guidance at the beginning concerning what literature to read and what methods might be appropriate. You then go away and write the proposal. 1-2 weeks before the deadline you should give the proposal to the supervisor, who will correct it once only. Then you hand it in. It is often convenient to write a proposal in a lab in which you are working, since then you can ask other people in the lab for help. (Asking lab members for help is an extremely important research skill!) The proposal subject (and lab) can be completely different from your final Masters thesis topic.
You do a six-week practical in a lab of your choice (within MCB). This must be written up as a formal report with Introduction, Methods, Results and Discussion, references. Also you should do a presentation in the laboratory seminar series – either presenting you project, or a literature presentation. All of this will be marked by the supervisor.
PLEASE NOTE: For administrative reasons it is important that the proposals and practical reports are corrected promptly, so I will ask you to register for this module centrally. We submit all the results for module 4 to the faculty together, so a delay by one person affects everyone. The deadline will be September 18th 2015.
MARKING of project proposals and lab rotations
The project proposal and lab rotation MUST be marked on the official forms. I will send you these in March. Informal e-mails from the supervisors cannot be accepted.
MODULE 5 Biolab
This is a lab practical of 8 weeks within MCB. This must be written up as a formal report with Introduction, Methods, Results and Discussion, references. Also you should do a presentation in the laboratory seminar series – either presenting your project, or a literature presentation. This will be marked by the supervisor who must be a recognised MCB teacher.
MODULE 6 Working in Biosciences
This is a lab practical of 8 weeks that can be done at any approved location. Before setting up a trip elsewhere please check with me. Please, please do NOT plan to leave the country before finishing module 4!!!
As for Module 5, the lab practical MUST be written up as a formal report with Introduction, Methods, Results and Discussion, references. Also you must do a presentation in the laboratory seminar series – either presenting you project, or a literature presentation. Everything will be marked by the supervisor. If you do this module in another country, the supervisor should give a mark on the scale used in that country but also say what percentile you fall into (e.g. bottom 50%, top 5% etc.).
IMPORTANT.When you return I must see the formal report in order to make sure that the mark is appropriate according to our standards. If necessary I will “translate” the grade into an equivalent in our system. Because of this, it is ESSENTIAL that you make it absolutely clear which experiments you did yourself. It is NOT appropriate to write "We" all the way through a report. Instead, if you did something, write "I did this" Use "we" ONLY if you did something with someone else. Otherwise, actually, you are lying!!!
If you stay in a lab for more than 8 weeks you should make it clear which work was done in the last 8 weeks, since officially, only 8 weeks should be used for the purposes of grading.
Normally, the MSc thesis work is done in the lab of an MCB teacher/lecturer. PEople with status "A" or "B" are allowed to supervise and examine the MSc thesis. To find the current list go to:
Examination is by writing a thesis and giving an oral presentation.
Students are now also allowed to do their MSc thesis in an external laboratory. However if they do this they must find both primary, and secondary supervisors from within the list of MCB examiners. These names are submitted before the thesis work starts. Please note that this is a both a considerable responsibility, and a thankless chore for the MCB examiners concerned, so finding someone to do it may be difficult.
IMPORTANT. You must register for your Masters thesis within 6 weeks of finishing modules 1-6. If you wish to postpone registering then you must make sure that you can delay submitting the protocol (or result) for either module 5 or module 6.
Lecturer: Christine Clayton.
This seminar focusses mainly on small molecule drug development, but also includes novel approaches such as therapeutic RNAs.
It is preceded by two lectures that introduce drug development.
Organelle dynamics in health and disease
LeAnne-Lore Schlaitz, Carmen Nussbaum.
Special exchange programme: Life Science for Health (LSH)
Selected Heidelberg students will be able to spend part of Semester 3 in either the Karolinska Institute, Stockholm or the University Medical Centre Leiden, The Neth
erlands. The LSH program allows for the exchange of students studying in Master programmes in the three institutions.
Structure of 3rd semester (click to view larger image in new window)
Structure of 4th semester (click to view larger image in new window)