Stefan Björklund - Professor
The Mediator complex and its function in transcriptional regulation at the molecular level
Tumor development is usually caused by changes of the levels, the expression pattern or the activity for one or several proteins. These changes are often a result of mutations of certain genes i.e. proto-oncogenes and tumor suppressor genes. These genes normally function as a template for the synthesis of proteins that in the normal, healthy cell function as master regulators of larger families of genes. Another function for proto-oncogenes and tumor suppressor genes is to encode for proteins that control cell division. This process must proceed in a controlled manner where one process must be completed before the next process is initiated. A common cause for tumor development is mutations in the genes that encode these control proteins which then leads to miss-expression of other proteins and uncontrolled cell division. Knowledge about the basic mechanisms that control how transcription is regulated is therefore fundamental to reveal the underlying mechanisms behind most tumors, and in the long run for the possibility to develop drugs to treat different cancer.
In this project we combine structural and functional studies of a set of ~25 proteins which assemble in a large complex called Mediator. The mediator complex is essential for regulated transcription of nearly all genes in all eukaryotes from yeast to humans by transferring signals from promoter-bound transcriptional regulators to the general RNA polymerase II transcription machinery. Our aim is to reveal how Mediator functions at the molecular level in order to understand (and to influence) how transcription of genes is regulated.
We have chosen to work with two different model systems; the yeast Saccharomyces cerevisiae and the plant Arabidopsis thaliana. There are several reasons for this choice. First, basic mechanisms like replication, transcription and translation are usually well conserved between eukaryotes. Second, these systems are well suited for these types of studies. Yeast has the advantage of being easily manipulated by genetic methods which combined with biochemical methods offer unique possibilities to reveal complicated mechanisms. The plant system is interesting for studies of transcriptional regulation since plants, different to most other organisms, cannot respond to harsh environments by movement, but rather has to adapt by changing their gene expression pattern.