Research


Projects

Cell cycle and mitotic fidelity
The cell cycle comprises a series of processes, like DNA duplication and nuclear division, which lead to the formation of two daughter cells from one mother cell. These events are highly similar even between evolutionarily distant organisms, such as the unicellular fission yeast and humans. Cell cycle progression is tightly regulated and coordinated, and defects in these processes can lead to cancer. In fission yeast, failed coordination between nuclear division and cytokinesis may lead to catastrophic mitosis and the so-called „cut“ (cell untimely torn) phenotype, where the division septum forms aberrantly across an undivided nucleus. Several classes of „cut“ mutants have been described, including some lipid metabolism genes. We have identified Cbf11, a fission yeast CSL-family transcription factor, as a transcriptional regulator of lipid metabolism genes important for mitotic fidelity. Our current research aims to clarify the connection between lipid metabolism and catastrophic mitosis.



Figure 1 - Fluorescence microscopy of fixed WT and lipid metabolism mutant fission yeast cells demonstrates how Cbf11 (transcription factor) and its target Cut6 (acetyl-coenzyme A carboxylase) are required for proper execution of mitosis. Cells were stained with DAPI to visualize DNA. Asterisks mark cells in which catastrophic mitosis occurred and the nucleus was cut by the prematurely formed division septum. White bar represents 10 micrometers.








Response to stress and nutrient availability
Changes in the environment, such as the presence of toxins or depletion of nutrients, pose constant challenges to cells. Furthermore, harmful insults can also come from within the cell, as exemplified by the generation of reactive oxygen species during respiration. In order to survive, cells need to deal with various stressful conditions, either by neutralizing the stressor or by physiological adaptation. To this end, elaborate signalling pathways have evolved that allow cells to sense and respond to stress.
Oxidative stress represents a complex and intensely studied phenomenon tightly linked to a range of human diseases. Despite considerable research efforts, the cellular and organismal responses to oxidative stress are not completely understood. In fission yeast, the response to oxidative stress is mainly mediated by two pathways: 1) the MAP kinase Sty1/p38 pathway, and 2) the redox-sensitive transcription factor Pap1/AP-1. We aim to identify additional regulatory components in these signalling networks, and how these respond to changes in nutrient availability.



Figure 2 - Hierarchical clustering of 340 fission yeast genes showing differential expression under various cultivation conditions (different media, growth phases, genetic perturbations) identified distinct patterns in regulation of oxidative stress-response genes.
















Publications

2016
Převorovský M, Hálová M, Abrhámová K, Libus J, Folk P.
BioMed Research International. 2016. doi:10.1155/2016/4783841

Bischof L, Převorovský M, Rallis C, Jeffares DC, Arzhaeva Y, Bähler J.
Biotechniques. 2016 Oct 1;61(4):191-201.

Převorovský M, Oravcová M, Zach R, Jordáková A, Bähler J, Půta F, Folk P.
Cell Cycle. 2016 Sep 29:0.

2015
Převorovský M, Oravcová M, Tvarůžková J, Zach R, Folk P, Půta F, Bähler J.
PLoS One. 2015;10(9):e0137820.

The genomic and phenotypic diversity of Schizosaccharomyces pombe.
Jeffares DC, Rallis C, Rieux A, Speed D, Převorovský M, Mourier T, Marsellach FX, Iqbal Z, Lau W, Cheng TMK, Pracana R, Mülleder M, Lawson JLD, Chessel A, Bala S, Hellenthal G, O’Fallon B, Keane T, Simpson JT, Bischof L, Tomiczek B, Bitton DA, Sideri T, Codlin S, Hellberg JEEU, van Trigt L, Jeffery L, Li J-J, Atkinson S, Thodberg M, Febrer M, McLay K, Drou N, Brown W, Hayles J, Carazo Salas RE, Ralser M, Maniatis N, Balding DJ, Balloux F, Durbin R, Bähler J.
Nature Genetics (2015) doi:10.1038/ng.3215.

2014
Převorovský M.
Yeast. 2014 Nov 13. doi: 10.1002/yea.3055.

Bušek P, Převorovský M, Křepela E, Šedo A.
pp 317-395 in Glioma Cell Biology, Part II, Editors: Šedo A, Mentlein R, 2014
ISBN: 978-3-7091-1430-8

2013
Oravcová M, Teska M, Půta F, Folk P, Převorovský M.
PLoS One. 2013;8(3):e59435

2012
Pancaldi V, Saraç OS, Rallis C, McLean JR, Převorovský M, Gould K, Beyer A, Bähler J.
G3 (Bethesda). 2012 Apr;2(4):453-67.

2011
Převorovský M, Rallis C.
Genome Biol. 2011;12(5):305.

Převorovský M, Atkinson SR, Ptáčková M, McLean JR, Gould K, Folk P, Půta F, Bähler J.
PLoS One. 2011;6(8):e23650.

2009
Převorovský M, Groušl T, Staňurová J, Ryneš J, Nellen W, Půta F, Folk P.
Exp Cell Res. 2009 May 1;315(8):1533-47.

Převorovský M, Staňurová J, Půta F, Folk P.
FEMS Microbiol Lett. 2009 Apr;293(1):130-4.

2007
Převorovský M, Půta F, Folk P.
BMC Genomics. 2007 Jul 13;8:233.

2003
Převorovský M, Půta F.
Biotechniques. 2003 Oct;35(4):698-700, 702.

Funding

Current
Charles University (PRIMUS/MED/26 - New interconnections between lipid metabolism and centromeric heterochromatin function, 2017-2019)
Charles University (GAUK 1170217 - Mitochondrial hormesis in Schizosaccharomyces pombe: alternative mechanisms of prolonging chronological lifespan, 2017-2019)
Charles University (GAUK 1308217 - Evolutionary plasticity: Notch-independent CSL signaling and lipid metabolism, 2017-2019)
Charles University (UNCE 204013; SVV 260206)

Past
Grant Agency of the Charles University (GAUK 640413 - Characterization of DNA binding of CSL transcription factors in the yeast Schizosaccharomyces pombe, 2013-2015)
Czech Science Foundation (P305/12/P040 - Fission yeast CSL proteins in the maintenance of genome integrity, 2012-2014)
Grant Agency of the Charles University (92009 - Identification of CSL-responsive genes in Schizosaccharomyces pombe, 2009-2011)
Grant Agency of the Charles University (157/2005/B-BIO/PrF - The function of the CBF1 homolog from S. pombe – tracking the ancestral role of an important transcription factor, 2005-2006)