Cell populations achieve size homoeostasis by coordinating cell growth and division. Direct
(sizer) or indirect (adder, timer) models of size regulation have been proposed. Early experiments
from 1970s showed that fission yeast implements an almost perfect sizer, whereas more
recent data hint at looser regulation. It is unclear whether external conditions can affect regulation
stringency and putative additional internal thresholds or timers regulating cell cycle
progression. Moreover, it is currently unclear what causes different size heterogeneity levels
observed by varying experimental conditions.
In this work, I implemented an experimental and computational pipeline to investigate the
aforementioned points. First, I created a cell cycle reporter strain and devised an imaging
pipeline for analysing cells images, which I employed for acquiring high-throughput phenotypic
data on cells grown in different experimental conditions (nitrogen sources). Second, I wrote
cell cycle models and optimization scripts for extracting additional dynamic information from
static experimental data, e.g. regarding cell size regulation.
Apart from confirming that fission yeast adopts an imperfect sizer mechanism (at the G2/M
transition), I unexpectedly observed that sizer stringency increases in faster-growing populations
and is responsible for the reduction in heterogeneity of cell length at division. I also found
that a constant adder regulates G1 elongation and a timer determines S duration.
Fission yeast cells elongate asymmetrically; I found that elongation asymmetry depends on
growth rate and on the stage in which cells divided. I also observed the presence of slower
growing subpopulations, whose rate ranges between 15-40% of the overall growth rate and
whose abundance increases in least favourable conditions. Finally, I found that the duration of
the non-elongating phase between mitosis and cell division depends on growth rate, as well as
the duration of cell cycle stages in the elongating phase and the duration of the mitotic phase.