CONTACTS

Institute of Microbiology of CAS
Vídeňská 1083
142 20 Prague 4
Czech Republic
PHONE: +420 241 062 503
FAX: +420 241 062 501

oCellaris - usefull SW to analyse pH and stress granules in yeast

MEMBERS

Jiří Hašek, PhD. (head) hasek [at] biomed.cas.cz +420 241 062 503
Pavla Binarová, PhD., binarova [at] biomed.cas.cz +420 241 062 130
Ivana Malcová-Janatová, PhD. janatova [at] biomed.cas.cz +420 241 062 769
Jana Vojtová, PhD. vodolan [at] biomed.cas.cz +420 241 062 504
Lucie Trögelová (Kohoutová), PhD. troglova [at] biomed.cas.cz (maternity leave) +420 241 062 130
Jana Chumová, PhD. chumova [at] biomed.cas.cz +420 241 062 130
Lenka Senohrábková, MSc. (PhD student) senohra [at] biomed.cas.cz +420 241 062 590
Hana Kourová, MSc. (PhD student) kourova [at] biomed.cas.cz +420 241 062 130
Renata Lejsková, MSc. (PhD student) rslaba [at] biomed.cas.cz (maternity leave) +420 241 062 590
Dominik Eisner, BSc. (Diploma student) dominik.ei [at] seznam.cz +420 241 062 504
Danuša Hašková, MSc. (technician) danusa.haskova [at] biomed.cas.cz +420 241 062 590
Dana Janošková, MSc. (technician) dana.janoskova [at] seznam.cz +420 241 062 590
Lenka Nováková, MSc. (technician) lenkan [at] biomed.cas.cz +420 241 062 590
Gabriela Kočárová, MSc. (technician) kocarova [at] biomed.cas.cz +420 241 062 130
Jarmila Serbousková (part-time technician) +420 241 062 503

RESEARCH TOPICS

i) Stress granules and misfolded proteins/prions.
ii) Stress granules and protein degradation.
iii) Stress granules and cytoskeleton.
 
 

CURRENT PROJECTS

Heat-induced stress granules in S. cerevisiae

Environmental changes induce stress response in live cells. As a consequence of these stresses, various intracellular accumulations containing protein and ribonucleoprotein complexes are formed. Malfunction in cleansing these accumulations may result in various functional and metabolic disorders at the cellular level.

Robust stresses induce a transient accumulation of translation machinery into stress granules (SGs). Complexity of these SGs indicate that their dynamics vary depending on the cell type and applied stress, and alteration of their constitutive components may result in persisting and possibly harmful protein accumulations detected in several human pathologies from cancer to neurodegeneration. An important question remains, whether assembly of heat-induced SGs is good or bad for yeast cells to cope with heat.

Yeast Saccharomyces cerevisiae represents a suitable model system to elucidate the bases of these disorders. Our studies on heat-shocked yeast S. cerevisiae indicate that heat-induced SGs assembly depends on polysome-free mRNA. Heat-induced SGs also associate with misfolded proteins and sequester particular signaling and regulatory proteins. In our studies, we combine live-cell-imaging with biochemical and genetic approaches to analyze dynamics of heat-induced SGs in specific yeast mutants. We want to understand the impact altered SGs assembly on heat-stress survival. We assume that our analysis of heat-stressed yeast cells will produce important new insights into SGs biology and stress survival that will be instrumental to further studies also in the mammalian systems.

Role of gamma tubulin in stress response

γ-Tubulin is a phylogenetically conserved member of tubulin superfamily, involved in nucleation of microtubules from spindle pole bodies or centrosomes. Current models of mitotic spindle formation in the absence of centrosomes are based on chromatin-mediated microtubule organization and nucleation from pre-existing microtubules; however, molecular mechanisms behind the process are much less understood. Characterization of molecular components of γ-tubulin complexes and identification of interacting proteins and their function in acentrosomal microtubule organization present a long term goal of our research team. We described interaction of TPX2 protein with γ-tubulin and function of RanGTPase pathway in plant microtubule formation as well as function of MAP kinases in regulation of cell division through γ-tubulin and microtubule plus end proteins EB1c. Role of γ-tubulin in genome maintenance in response to DNA damage is under study. 
 

2017 - Prague - 28th International Conference on Yeast Genetics and Molecular Biology

FUNDING

The projects are financially supported by the following institutions:
Czech Science Foundation: 16-05497S (JH), P501 15-11657S (PB)

COLLABORATION

NICHD NIH, Bethesda, USA (Dr. A. Hinnebusch)
University of Salzburg, Austria (Prof. M. Breitenbach, Dr. M. Rinnerthaler)
St John's University, New York, USA (Dr. Ales Vancura)
University of New Hampshire, Durham, USA (Dr. Clyde L.Denis)
Swedish University of Agricultural Sciences, Uppsala, Sweden (G. Daniel)
University of London, UK (L. Bögre)
Semmelweis University, Budapest, Hungary (T. Mészáros)

RECENT PUBLICATIONS

Bischof J., Salzmann M., Streubel M.K., Hasek J., Geltinger F., Duschl J., Bresgen N., Briza P., Haskova D., Lejskova R., Sopjani M., Richter K., Rinnerthaler M. (2017) Clearing the outer mitochondrial membrane from harmful proteins via lipid droplets. Cell Death Discovery (2017) 3, 17016; doi:10.1038/cddiscovery.2017.16/p>

Horvath, B., Kourova, H., Nagy S., Nemeth S., Magyar Z., Papdi C., Ahmad Z., Sanchez-Perez G., Perilli S., Blilou I., Meszaros T., Binarova P., Bogre L., Scheres B. (2017) Arabidopsis RETINOBLASTOMA RELATED regulates DNA damage response independently of the cell-cycle.EMBO Journal in press

Vasicova P., Rinnerthaler M., Haskova D., Novakova L., Malcova I., Breitenbach M., Hasek J. (2016) Formaldehyde fixation is detrimental to actin cables in glucose-depleted S.cerevisiae cells. Microbial Cell in press

Malcova I., Farkasovsky M.,Senohrabkova L., Vasicova P., Hasek J. (2016) New integrative modules for multicolor-protein labeling and live-cell imaging in Saccharomyces cerevisiae. FEMS Yeast Research, 16, doi: 10.1093/femsyr/fow027

Wang X., Xi W., Toomey S., Chiang Y-C.,Hasek J., Laue T.M., et al. 2016) Stoichiometry and Change of the mRNA Closed-Loop Factors as Translating Ribosomes Transit from Initiation to Elongation. PLoS ONE 11(3): e0150616. doi:10.1371/

Vasicova P., Lejskova R., Malcova I., Hasek J. (2015) The stationary phase cells of S. cerevisiae display dynamic actin filaments required for processes extending chronological life span . Mol. Cell. Biol. 35, 3892-3908.

Grousl T., Opekarova M., Stradalova V., Hasek J., Malinsky J.(2015) Evolutionarily conserved 5'-3' exoribonuclease Xrn1 accumulates at plasma membrane-associated eisosomes in post-diauxic yeast. PLoS ONE 10, e0122770.

Rinnerthaler M., Lejskova R., Grousl T.,Stradalova V., Heeren G., Richter K., Breitenbach-Koller L., Malinsky J., Hasek J., Breitenbach M. (2013) Mmi1, the yeast homologue of mammalian TCTP, associates with stress granules in heat-shocked cells and modulates proteasome activity.PLoS ONE 8, e77791.

Malinsky J., Opekarova M., Grossmann G., Tanner W. (2013) Membrane Microdomains Rafts, and Detergent-Resistant Membranes in Plants and Fungi. Annu. Rev. Plant. Biol. 64, 501-529. doi:10.1146/annurev-arplant-050312-120103

Grousl T., Ivanov P., Malcova I., Pompach P., Frydlova I., Slaba R., Senohrabkova L., Novakova L., Hasek J. (2013) Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae. PLoS ONE 8, e57083.

Gaur N.A., Hasek J., Brickner D.G., Qiu H., Zhang F., Wong C.M., Malcova I., Vasicova P., Brickner J.H., Hinnebusch A.G. (2013)Vps factors are required for efficient transcription elongation in budding yeast. Genetics 193, 829–851

Vasicova P., Stradalova V., Halada P., Hasek J., Malcova I. (2013) Nuclear import of chromatin remodeler Isw1 is mediated by atypical bipartite cNLS and classical import pathway. Traffic 14,176-93. doi: 10.1111/tra.12025. Epub 2012 Nov 26.

Rinnerthaler M., Büttner S., Laun P., Heeren G., Felder T.K., Klinger H., Weinberger M., Stolze K., Grousl T., Hasek J., Benada O., Frydlova I., Klocker A., Simon-Nobbe B., Jansko B., Breitenbach-Koller H., Eisenberg T., Gourlay C.W., Madeo F., Burhans W.C., Breitenbach M. (2012) Yno1p/Aim14p, a NADPH-oxidase ortholog, controls extramitochondrial reactive oxygen species generation, apoptosis, and actin cable formation in yeast Proc. Natl. Acad. Sci. USA 29, 8658-8663

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