"To work in the service of life and the living, in search of the answers to questions unknown"
                      John Denver

The Proteosynthesis and Proteostasis group is a part of the Laboratory of Cell Signalling of the Institute of Microbiology of the Czech Academy of Sciences.

Our goal is to search for and describe mechanisms which regulate protein synthesis and related stress response. We are, in particular, interested in RNA granules (stress granules and Processing bodies) as well as in misfolded protein aggregates.

Yeast cells (Saccharomyces cerevisiae) and mammalian tissue cultures are our model organisms.  

Stress granules (SGs) are transient membrane-less organelles consisting mainly of messenger ribonucleoprotein assemblies. The formation of SGs results from an evolutionarily conserved proteostasis strategy to cellular stress. During their formation triggered by robust environmental stress, SGs sequester translationally inactive mRNA molecules, which are either forwarded for further processing elsewhere or stored during stress within SGs. Removal of mRNA molecules from active translation and their sequestration in SGs allows preferential translation of stress response transcripts. By affecting the specificity of mRNA translation, mRNA localization and stability, SGs are involved in overall cellular reprogramming during environmental stress.

Processing bodies (P-bodies) are messenger ribonucleoprotein assemblies similar to SGs. However, unlike SGs, P-bodies are found in unstressed cells and propagate when subjected to stress. P-bodies accumulate translationally repressed mRNA molecules and mRNA decay machinery components. Due to their composition, it was generally believed that P-bodies regulate the degradation of mRNA molecules. However, recent data showed that mRNA degradation occurs independently on P-bodies. Although P-bodies involvement in mRNA quality control, mRNA storage, and translation repression was documented, their general function in cell metabolism remains elusive.

Along with the formation of SGs and P-bodies upon environmental stress, proteostasis is maintained by molecular chaperons which recognise misfolded proteins. These proteins are refolded or degraded by the ubiquitin-proteasome pathway or autophagy. The misfolded proteins can also be sequestered into distinct subcellular compartments, where they are retained during stress alleviating an overloaded protein folding system.