Biophysical Methods & Structural Biology

Course goals

1. Describe the basic principles of the experimental methods treated in the course, i.e. light microscopy, EM, MS, NMR, and XRD.
2. Identify the appropriate experimental methods for a given research question;
3. Critically assess the outcome of a quantitative data analysis;
4. Search, access, view and evaluate atomic models of biomolecules with common database search tools and software packages;
5. Assimilate biophysical and structural data from multiple methods to formulate molecular mechanisms and models of biomolecular organization;
6. Analyse, perform literature searches and report on the biomolecular organization of a biological system;
7. Effectively work collaboratively in a group assignment with their peers and reflect on their role in this collaboration.

Content

In this course students study the basic principles underlying biophysical and structural biology methods such as light and electron microscopy and different forms of spectroscopy. Students practice with real data and in doing so, learn how to interpret the quality of quantitative data based on key figures-of-merit and how this quality relates to the biological information that can be extracted from the data. 
 
Set up of this course: In this course plenary lectures, group work, and individual computer practicals all contribute to a deep learning experience aimed at familiarizing students with the theory behind, and applications of, microscopy and spectroscopy in structural biology. One aspect all techniques have in common is that data analysis is a crucial step in the experimentation process. A theoretical basis for the retrieval of useful biological information from primary measurements and the assessment of data quality and information content is laid down in the plenary lectures.
 
In a series of context-rich lectures key insights into the molecular organization of life that these methods have brought us are discussed. In these lectures experimental challenges for microscopy and spectroscopy, other than data analyses, are covered (determining the structure and organisation of biological complexes; imaging live tissues and cells on relevant timescales; identifying biomolecules in a cellular context at the nanometer scale; uncovering biological interaction networks at a systems-wide scale.)
 
Information from the lectures is practiced and applied in weekly tutorials and several computer practicals
 
Throughout the course, students work on a case study about the biomolecular organization of a biological system of their choice. In this group assignment students explore this biological system by analysing and reviewing published literature (journal club style) and by retrieving and exploring molecular models from databases. In the final weeks of the course, students prepare a presentation to explain to their fellow students how various biophysical and structural biology methods were essential in providing the original researchers key insights into the molecular organization of their chosen system.

Relation to other courses: This course builds on (1) mathematical and programming skills introduced in MBLS-102 ‘Mathematics and Programming’ and applied in MBLS-106 ‘Biological Physics’, and on (2) MBLS-104 ‘Physical Chemistry for the Life Sciences’ in which basic concepts of NMR and MS are introduced. This course prepares students for the following level 2 and 3 courses ‘Advanced Structural Biology', ‘NMR spectroscopy and Molecular modelling’, ‘Mass Spectrometry and Proteomics’, and ‘Light and Electron Microscopy’.

Teaching formats course (estimation):
In this course lectures are alternated with computer practicals and tutorials. A context-rich group assignment is used to integrate the various aspects of this course in a final project.

Lectures = 60%
Tutorials (werkcolleges) = 25% 
Practicals = 10%
Presenting = 5%

Grading (see course manual for details):

1. Exam 1 (40%)
2. Exam 2 (40%)
3. Presentation on a case study (20%)

Participation in the computer practicals is required for admittance to the written exams.
The minimum grade required to pass the course is a 5 for each component (2 exams and the group presentation), with a weighted average score of at least 5.5.