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.


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Czech Science Foundation (20-12109S - The Unique Mycobacterial Transcription Machinery: Insights into its Composition, Structure & Functioning, 2020-2022)
Charles University Grant Agency (GAUK 248120 - Transcription regulators of lipid metabolism in the fission yeast Schizosaccharomyces pombe - mapping their target genes and their role in preventing catastrophic mitosis)
Charles University Grant Agency (GAUK 1311120 - Nitrogen source as a determinant of mitotic fidelity in fission yeast)
Charles University (SVV 260206)

Charles University (PRIMUS/MED/26 - New interconnections between lipid metabolism and centromeric heterochromatin function, 2017-2019)
Charles University Grant Agency (GAUK 1170217 - Mitochondrial hormesis in Schizosaccharomyces pombe: alternative mechanisms of prolonging chronological lifespan, 2017-2019)
Charles University Grant Agency (GAUK 1308217 - Evolutionary plasticity: Notch-independent CSL signaling and lipid metabolism, 2017-2019)
Charles University (UNCE 204013)
Charles University Grant Agency (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)
Charles University Grant Agency (GAUK 92009 - Identification of CSL-responsive genes in Schizosaccharomyces pombe, 2009-2011)
Charles University Grant Agency (GAUK 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)