Research frontiers in molecular and structural biology

PhD-course for the PhD-school - November 8th to 19th, 2010

The course will cover topics of current interest in molecular and structural biology and is designed for PhD fellows at the PhD school in molecular and structural biology, but other PhD students who are seeking state-of-the art research strategies and methods are welcome. The course is divided into two major sections of two weeks duration. Each section consists of lectures from resident faculties and other invited speakers, discussions and demonstrations/tutorials. The first section covers structural biology including bioinformatics and RNomics. The research groups of this section are devoted to the study of (I) Bioinformatics for assemble, annotation and mining genomes (II) Modelling and drug design (III) structural-functional studies; (IV) RNA biology. The second section is focused on molecular biology. This section consists of research groups that are dedicated to the study of (V) Molecular and biological aspects of Systemic lupus erythematosus. (SLE) and SLE nephritis (VI) Study of transcription factor function by molecular genetics and use of zebrafish as a model system. VII) Gene expression: a journey from the cell membrane to the nucleus, and (VIII) Molecular characterization and functional role(s) of specific protein-protein interactions in intracellular signal transduction and transcriptional regulation.

Lecture plan and time-table 2010

The lectures are mandatory for the students.

Registration for the course by an e-mail to Gry Evjen (Gry.Evjen@uit.no) within October 25th, 2010.

Questions about the course can be directed to one of the group leaders of the PhD-school, or to Gry Evjen, NorStruct (gry.evjen@uit.no).

Evaluation/exam
Each candidate will be assigned a research paper on one of the topics covered by the course. The topic will be chosen outside the PhD-student’s own research field. The evaluation will be based on a 20 minute presentation of the research paper, followed by questions from an evaluation panel. The presentation will be judged by these criteria.

The research group suggesting the paper will act as mentors for the PhD-student in the process of preparing the presentation.

The course participants will have the topic announced one week prior to the start of the course, and the presentation/evaluation will be held on November 19th, 2010.

Evaluation: bestått/ikke-bestått

Lecture plan for "Research frontiers in molecular and structural biology" - Autumn 2010

Schedule

The lecture notes for the course will be available, and will constitute the syllabus for the course.

The topics of the course:

I) Macromolecular structures at atomic resolution – experimental methods

Arne Smalås
Norwegian Structural Biology Center (NorStruct)

From genes to structure to function
This section of the course will cover modern methods and strategies used in structural biology. The process from a potential interesting gene or gene cluster is identified - to the confirmation of function from 3D-structures at atomic levels in combination with biochemical, biophysical and computational methods, will be discussed – including the concept of structural genomics. Furthermore, some central techniques for obtaining structural information at atomic resolution will be covered, and how the structural data can be combined with other methods in order to extract structure-function relation information. Structure-function relations studies will be exemplified by examples.

II) Molecular modelling of drug target proteins

Ingebrigt Sylte
Molecular Modelling Group

Structural knowledge is essential for the understanding of how drugs interfere with cellular communication and regulation, and for the design of new ligands with a potential therapeutic potential. Experimental techniques for direct structural determination are time consuming and not always strait forward. The lack of detailed experimental structures limits the design of new ligands that interfere with protein function and disease processes. Molecular modelling may provide structural insight into the processes of drug recognition and binding, and be an important support to experimental studies. In this section computer based methods for generating 3D models of proteins based on indirect structural information are discussed and exemplified. Molecular modelling techniques for predicting binding affinities and binding modes are also discussed and exemplified.

III) Ribozymes – structure and function

Steinar Johansen
RNA & Transcriptome Research Group

Many RNA molecules are directly involved in cell function due to their complex three-dimensional structure. During the past decade new technologies have become available which greatly improves RNA structure prediction and determination. The first part of this section will review recent knowledge from the literature of RNA structure, including large catalytic RNA molecules as well as the ribosome. Then, current examples from our research group on RNA structure determination of a lariat-forming ribozyme will be introduces. In the second part the catalytic diversity of RNAs will be presented. Examples from the literature will be extended with our own research. Here, molecular methods used to study RNA catalysis in the lab will be presented.

IV) Bioinformatics and computational biology

Nils Peder Willassen
Molecular Biosystems Group & The Norwegian Structural Biology Center (NorStruct)

This section of the course will cover methods and strategies used in functional genomics to understand how microorganisms behave under different environmental conditions. We will also give a short introduction to system biology using Vibrio salmonicida as a model organism.

V) Molecular and biological aspects of SLE and SLE nephritis

Ole Petter Rekvig
Molecular Immunology Research Group

The kidney disease lupus nephritis is the most serious manifestation of the autoimmune syndrome Systemic lupus erythematosus. Lupus nephritis is caused by the interaction of autoimmune nucleosome-specific autoantibodies and T cells. The activation of autoimmune B cells and T cells can be described at an experimental level, but the in vivo processes are still enigmatic. The potential of intraglomerular cell death by apoptosis (and necrosis?) to provide activators for the autoimmune responses, and simultaneously serve as target antigens in the glomeruli will be discussed. Lupus nephritis will in this section be used as a model system to demonstrate how biotechnology, cell biology and gene technology are utilized to explain a serious disease manifestation in a human disease.

The theoretical basis for lupus nephritis:

1. Immunological tolerance:
    - Principles for regulation towards nucleosomes
    - Consequence of loss of tolerance
2. Apoptosis – basic aspects
3. Nephritis – an apoptosis disease in SLE

Methods that will be focused on in this section:

4. Co-localization immune electron microscopy
5. Biacore Surface Plasmon Resonance

VI) Study of transcription factor function by molecular genetics and use of zebrafish as a model system.

Ingvild Mikkola
Molecular Genetics Research Group

Transcriptionfactors are regulatory proteins that activate or repress the expression of their respective target genes. The complete sequence of the human, mouse and zebrafish genomes are now accessible in databases, and are (in combination with more conventional laboratory techniques) used for the study of gene regulatory regions. This session will give an overview of techniques used to study transcription factors, and provide examples on the usefulness of a modelsystem like the zebrafish.

VII) Gene expression: a journey from the cell membrane to the nucleus

Ugo Moens and Mona Johannessen
The Cellular Signalling and Gene Regulation Research Group

The aim of this modul is, by using the transcription factor CREB (cAMP response element binding protein) as an example, to illustrate in detail the participation of signal transduction pathways, chromatin structure, protein-protein interaction and protein modifications in the regulation of gene expression.

Transcription of mammalian protein encoding genes relies on complex events that involve i. signal transduction pathways regulating the activity of transcription factors, ii. DNA elements controlling the accessibility of the DNA, iii. protein-protein interactions and post-translational modifications influencing transcription factor activity. The transcription factor CREB, which is estimated to affect the transcription of approximately 4000 genes, will be used as an example to illustrate the multiple mechanisms participating in gene expression. Examples of the implication of CREB in cellular processes and diseases will be presented.

VIII) Molecular characterization and functional role(s) of specific protein-protein interactions in intracellular signal transduction and transcriptional regulation.

Terje Johansen and Geir Bjørkøy
Molecular Cancer Research Group

All aspects of cellular behaviour are under strict control. External signals are integrated into intracellular signalling pathways that regulate both metabolic processes and gene expression. Loss of control over these signalling pathways is the underlying cause of severe diseases such as cancer and diabetes. The specificity and magnitude of a certain signal is obtained through highly specific protein-protein interactions.
In these lectures we will exemplify both theoretic and experimental aspects of signal transduction and gene regulation. We will focus on some PB1 domain proteins in intracellular signalling. Aspects of studies of transcription regulation will be exemplified by our work with the specific transcription factor Pax6 and the transcriptional co-activator/co-repressor SPBP.