Akos Sveiczer

A stochastic, molecular model of the fission yeast cell cycle: role of the nucleocytoplasmic ratio in cycle time regulation

We propose a stochastic version of a recently published, deterministic model of the molecular mechanism regulating the mitotic cell cycle of fission yeast, Schizosaccharomyces pombe. Stochasticity is introduced in two ways: (i) by considering the known asymmetry of cell division, which produces daughter cells of slightly different sizes; and (ii) by assuming that the nuclear volumes of the two newborn cells may also differ. In this model, the accumulation of cyclins in the nucleus is proportional to the ratio of cytoplasmic to nuclear volumes. We have simulated the cell-cycle statistics of populations of wild-type cells and of wee1(-) mutant cells. Our results are consistent with well known experimental observations.

The time-profile of cell growth in fission yeast: model selection criteria favoring bilinear models over exponential ones

BackgroundThere is considerable controversy concerning the exact growth profile of size parameters during the cell cycle. Linear, exponential and bilinear models are commonly considered, and the same model may not apply for all species. Selection of the most adequate model to describe a given data-set requires the use of quantitative model selection criteria, such as the partial (sequential) F-test, the Akaike information criterion and the Schwarz Bayesian information criterion, which are suitable for comparing differently parameterized models in terms of the quality and robustness of the fit but have not yet been used in cell growth-profile studies.ResultsLength increase data from representative individual fission yeast (Schizosaccharomyces pombe) cells measured on time-lapse films have been reanalyzed using these model selection criteria. To fit the data, an extended version of a recently introduced linearized biexponential (LinBiExp) model was developed, which makes possible a smooth, continuously differentiable transition between two linear segments and, hence, allows fully parametrized bilinear fittings. Despite relatively small differences, essentially all the quantitative selection criteria considered here indicated that the bilinear model was somewhat more adequate than the exponential model for fitting these fission yeast data.ConclusionA general quantitative framework was introduced to judge the adequacy of bilinear versus exponential models in the description of growth time-profiles. For single cell growth, because of the relatively limited data-range, the statistical evidence is not strong enough to favor one model clearly over the other and to settle the bilinear versus exponential dispute. Nevertheless, for the present individual cell growth data for fission yeast, the bilinear model seems more adequate according to all metrics, especially in the case of wee1 Δ cells.

How do fission yeast cells grow and connect growth to the mitotic cycle

To maintain size homeostasis in a unicellular culture, cells should coordinate growth to the division cycle. This is achieved via size control mechanisms (also known as size checkpoints), i.e. some events during the mitotic cycle supervene only if the cell has reached a critical size. Rod-shaped cells like those of fission yeast are ideal model organisms to study these checkpoints via time-lapse microphotography. By applying this method, once we can analyse the growth process between two consecutive divisions at a single (or even at an ‘average’) cellular level, moreover, we can also position the size checkpoint(s) at the population level. Finally, any of these controls can be abolished in appropriate cell cycle mutants, either in steady-state or in induction synchronised cultures. In the latter case, we produce abnormally oversized cells, and microscopic experiments with them clearly show the existence of a critical size above which the size checkpoint ceases (becomes cryptic). In this review, we delineate the development of our knowledge both on the growth mode of fission yeast and on the operating size control(s) during its mitotic cycle. We finish these historical stories with our recent findings, arguing that three different size checkpoints exist in the fission yeast cell cycle, namely in late G1, in mid G2 and in late G2, which has been concluded by analysing these controls in several cell cycle mutants.

Cell length growth patterns in fission yeast reveal a novel size control mechanism operating in late G2 phase

Because cylindrically shaped fission yeast cells grow exclusively at their tips, cell volume is proportional to length and can be easily monitored by time‐lapse microscopy. Here, we analysed the growth pattern of individual cells from several fission yeast strains to determine the growth function that describes them most adequately and to perform size control studies.

Is there a universal rule for cellular growth?--Problems in studying and interpreting this phenomenon.

There is an enormous number of different cells in the biosphere, prokaryotes and eukaryotes, many of them living as unicellular organisms, while others forming complex multicellular beings. Some cells grow and divide generating offsprings; others are in a dormant state or generate gametes or spores. It is not too hard to conclude that it is unlikely that there is a general law describing the growth kinetics of every cell considering that several of them do not grow at all. However, when unicellular microorganisms (like bacteria or yeasts) reside in a stirred liquid medium containing appropriate nutrients both in qualitative and quantitative terms, the pure culture soon reaches an exponential phase of growth where the cell number (or cell mass) increases exponentially in time (Black, ⇓). Notably, the known general growth kinetics of this asynchronous population tells us nothing about the growth kinetics of mass observed in the individual cells of the population. By the same logic, the ‘simplest’ way for the cells to grow is an exponential mode; however, there is no unequivocal proof that such a universal law exists. Theoretically, any continuous mathematical function might describe cellular growth, if it fulfils two requirements; namely, both cell mass must double during the cycle time, and also, the rate of cell mass increase must do the same – even if not necessarily for every individual cell – but at least for the hypothetical ‘average’ cell representing the population. This way, a symmetric cell division can generate two identical progenies whose physiological states are equivalent with each other as well as with that of their mother cells state at the beginning of the previous cycle (Mitchison, ⇓). The exponential model has the advantage that cell mass is automatically proportional to the rate of cell mass increase; therefore, there is no need …

Phylogenetic and comparative functional analysis of the cell-separation α-glucanase Agn1p in Schizosaccharomyces.

The post-cytokinetic separation of cells in cell-walled organisms involves enzymic processes that degrade a specific layer of the division septum and the region of the mother cell wall that edges the septum. In the fission yeast Schizosaccharomyces pombe, the 1,3-α-glucanase Agn1p, originally identified as a mutanase-like glycoside hydrolase family 71 (GH71) enzyme, dissolves the mother cell wall around the septum edge. Our search in the genomes of completely sequenced fungi identified GH71 hydrolases in Basidiomycota, Taphrinomycotina and Pezizomycotina, but not in Saccharomycotina. The most likely Agn1p orthologues in Pezizomycotina species are not mutanases having mutanase-binding domains, but experimentally non-characterized hypothetical proteins that have no carbohydrate-binding domains. The analysis of the GH71 domains corroborated the phylogenetic relationships of the Schizosaccharomyces species determined by previous studies, but suggested a closer relationship to the Basidiomycota proteins than to the Ascomycota proteins. In the Schizosaccharomyces genus, the Agn1p proteins are structurally conserved: their GH71 domains are flanked by N-terminal secretion signals and C-terminal sequences containing the conserved block YNFNA(Y)/HTG. The inactivation of the agn1(Sj) gene in Schizosaccharomyces japonicus, the only true dimorphic member of the genus, caused a severe cell-separation defect in its yeast phase, but had no effect on the hyphal growth and yeast-to-mycelium transition. It did not affect the mycelium-to-yeast transition either, only delaying the separation of the yeast cells arising from the fragmenting hyphae. The heterologous expression of agn1(Sj) partially rescued the separation defect of the agn1Δ cells of Schizosaccharomyces pombe. The results presented indicate that the fission yeast Agn1p 1,3-α-glucanases of Schizosaccharomyces japonicus and Schizosaccharomyces pombe share conserved functions in the yeast phase.