HANNELORE BREITENBACH-KOLLER: CUSTOMIZED PROTEIN SYNTHESIS
We have developed a screen that can be used to identify ribosomal proteins that specifically regulate a particular mRNA. We are now using this in a pilot project to study therapeutic interventions for a mutation in a gene that plays a role in the rare disease Epidermolyis bullosa.
Ribosomes are part of all cells and consist of ribosomal RNA (rRNA) and ribosomal proteins. In eukaryotic cells, i.e. from yeast cells to human cells, ribosomes consist of a large 60S and a small 40S subunit, which together form the 80S functional ribosome. The ribosome synthesizes (= translated) proteins according to the encoded information on the messenger RNA (mRNA), the small subunit containing the decoding center and the large subunit containing the protein synthesis function. A central aspect of the regulation of gene expression – that is, the control of when and where in a cell a certain mRNA is translated into a protein – is the regulation of translation. For some years now, the regulatory role of ribosomal proteins and other components of the translational apparatus in these processes has become increasingly clear. Our group studies the ribosomal proteins rpL10, rpS6 and the ribosome-associated protein Nmd3p.
For several years now, our research has focused on the translation-associated, functional characterization of human disease genes in the yeast model system. We are studying the autism-associated ribosomal protein rpL10 in cooperation with the DKFZ Heidelberg; and the expression of the LAMB3 gene, the mutated form of which plays a role in the blistering skin disease Epidermolyis Bullosa, in cooperation with EB Haus Austria / PMU and the University of Kent.
We have developed a personalized ribosome screen that enables us to identify ribosomal variants that exclusively and selectively increase or decrease the protein synthesis yield of a target mRNA. “Personalized ribosomes” can be generated by different experimental strategies. These translational control studies have led to the topic of controlling protein synthesis of these candidate genes in oxidative stress. Our work is documented in our publications.