Course catalogue doctoral education - HT19

  • Ansökan kan ske mellan 2019-04-15 och 2019-05-15
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Title Understanding and fighting disease using structural biology
Course number 3047
Programme 1-Ingår i flera program
Language English
Credits 3.0
Date 2019-04-01 -- 2019-04-12
Responsible KI department Institutionen för biovetenskaper och näringslära
Specific entry requirements BSc-level course in biochemistry and molecular biology
Purpose of the course The course will first introduce X-ray crystallography, electron microscopy (EM) and nuclear magnetic resonance (NMR) spectroscopy, the three main methodologies used to experimentally determine the three-dimensional (3D) structure of biological macromolecules. Doctoral candidates will then analyze how point mutations can cause diseases at the molecular level and gain a basic understanding of how knowledge of the 3D structure of proteins can inform the drug design process.
Intended learning outcomes By following this course, doctoral candidates will learn how the 3D structure of proteins is determined, and how this information can be used to both understand human disease at the molecular level and facilitate the rational development of novel therapeutics. In particular, Ph.D. candidates will be able to understand the most important biochemical and biophysical properties of proteins and, based on this knowledge, learn to choose and apply protocols for expressing and purifying proteins for structural studies. Following the practicals, the candidates will also be able to bioinformatically analyze protein sequences and structures in order to predict their characteristics and functions.

At the end of the X-ray crystallography module, Ph.D. candidates will be able to read a protein crystallization diagram; list different crystallization techniques; understand the basics of X-ray diffraction; describe the data collection and processing procedures; explain the phase problem and its solution by experimental phasing or molecular replacement; understand the process of structure refinement; and validate crystal structures downloaded from the Protein Data Bank (PDB).

The electron microscopy module of the course will provide an introduction to the basics of EM. This knowledge will provide a foundation for understanding the technique and its applications. At the end of the module, the candidates will be able to understand the basics concepts of EM and its differences from other structure determination techniques; list the advantages and limitations of EM for structure determination; describe the overall functioning and instrumentation of an electron microscope; explain the interaction of electrons with the sample and the process of image formation; understand the principles of 3D reconstruction from projection images; compare the process of model building in EM with other structure determination techniques.

The NMR lecture will provide a basic overview of the technique as well as discuss the differences between NMR-derived models and those obtained by the other techniques. Thus, at the end of the lecture, the PhD candidates will be able to list the advantages and limitations of all methods presented and compare protein structures obtained through these different approaches.

After the last lecture, the doctoral candidates will be able to understand recent examples describing how human mutations can cause diseases by affecting the structure of proteins and their ability to perform their biological function. They will also have gained a basic knowledge of how lead compounds/drugs bind to their molecular targets, and how structural biology can be of high medical relevance by allowing to optimize the affinity and specificity of this interaction.
Contents of the course Theoretical: The lectures will open with an introduction to protein structure and function (1), followed by a presentation of protein expression and purification strategies (2). Then the theoretical background needed for understanding X-ray crystallography (3), EM (4) and NMR (5) will be given. At the end, we will go through examples of how gene mutations can lead to diseases and explain how knowledge of molecular structures can contribute to drug discovery (6). Practical: The Ph.D. candidates will work through six projects during the two weeks: (1) analysis of protein structure elements and properties using the molecular visualization program PyMOL; (2) protein purification; (3) protein structure determination by X-ray crystallography; (4) protein structure determination by EM; (5) comparison of protein structures obtained by X-ray crystallography, EM and NMR using PyMOL; (6) analysis of structure-function relationship for a selection of medically relevant proteins.
Teaching and learning activities Lectures, laboratory work, presentation and discussion of current biomedically relevant research in the field of structural biology.
Compulsory elements Lectures, laboratory work and seminar presentations are compulsory. If a Ph.D. candidate misses a practical exercise or the seminar presentations, they will be given a chance to complete it at another occasion set by the organizers.
Examination Reports from practical exercises and journal club-like presentations of scientific articles describing protein structure of biomedical interest. ILOs will be assessed both theoretically and through practical exercises. Each ILO will be tested through questionnaires that have to be submitted in electronic form at the end of each day. To ensure that each student gets every ILO, each teacher will take care of a maximum of 7 students; moreover, every ILO will be repeated on the day following the corresponding practical exercises and questionnaires, as well as when the students give their final presentations.
Literature and other teaching material Compendium containing a selection of recent structural biology studies relevant for biomedicine; protocols for practical work.
Number of students 8 - 14
Selection of students Selection will be based on 1) the relevance of the course syllabus for the applicant's doctoral project (according to written motivation), 2) date for registration as a doctoral student (priority given to earlier registration date).
More information The course will be given from Monday to Friday, 9 am to 5 pm. The address for the theoretical part is: NEO, Karolinska Institutet Campus Flemingsberg, Hälsovägen 7C, 14157 Huddinge. The address for the computer part is: KTH, Kungliga Tekniska Högskolan, Hälsovägen 11C, 14152 Huddinge. The course is arranged in collaboration between the doctoral programmes in Neuroscience and Development and Regeneration, see
Additional course leader Carsten Mim.
Earlier evaluation of the course Evaluation report
Course responsible Luca Jovine
Institutionen för biovetenskaper och näringslära
Contact person Eileen Dietzel
Institutionen för biovetenskaper och näringslära