Entry requirements

120 credits within the Master's Programme in Molecular Biotechnology Engineering including Linear Algebra and Geometry I, Structural Bioinformatics, and one of the courses Electromagnetism and Wave Physics or Applied Physics for Molecular Biotechnology. Proficiency in English equivalent to the Swedish upper secondary course English 6.

Learning outcomes

The course gives an introduction to methods for structure determination of biological macromolecules with special focus on diffraction based methods.

On completion of the course, the student should be able to:

• account for basic Fourier optics theory and its applications in structure determination of biological macromolecules
• account for basic theory and concepts used in structure determination by transmission electron microscopy (TEM), including cryo electron microscopy
• account for basic methods that are used in cryo electron microscopy structure determination
• account for basic concepts in X-ray crystallographic theory
• account for basic methods that are used in macromolecular crystallography
• build models of macromolecules by means of electron density maps and analyse the possible errors of such models by means of different validation methods
• critically review and evaluate structures solved with X-ray crystallography or cryo electron microscopy
• account for requirements, possibilities and limitations of different structure determination methods and for the information provided by the different methods.

Content

Basics

This course module covers basic concepts and theory of diffraction (both X-ray and electron diffraction) and Fourier optics and gives a basis to understand several of the most important methods for biomacromolecular structure determination (X-ray diffraction, cryo-EM). The concepts and the theory are developed, and are applied in later parts of the course.

Cryo electron microscopy

In this course module, theory and methodology for high resolution structure determination of biological macromolecules using cryo-EM are introduced. Students gain hands-on experience in processing cryo-EM data all the way from CTF correction to 3D classification and refinement.

X-Ray Crystallography

Here, the theory for X-ray crystallography and its application in modern methods for structure determination of biological macromolecules is further developed. Topics covered include collection and processing of data from synchrotron radiation sources, experimental phasing, interpretation of electron density maps and modelling, refinement and validation of structural models. Students will also get practical experience of all essential stages in a structure determination. The course module gives the students the knowledge and experience needed to critically review and evaluate structures solved with X-ray crystallography.

Other methods

Other complementary methods (e.g. XFEL single particle imaging, serial crystallography, SAXS/SANS) are introduced in a series of lectures.

Instruction

Lectures, literature seminars, laboratory sessions, computer exercises, and structure determination projects. Participation in seminars, laboratory sessions, computer exercises, and structure determination projects are compulsory.

Assessment

Written examination (6 credits). Seminars, exercises, laboratory sessions, and structure determination projects (4 credits).

If there are special reasons for doing so, an examiner may make an exception from the method of assessment indicated and allow a student to be assessed by another method. An example of special reasons might be a certificate regarding special pedagogical support from the disability coordinator of the university.