Biology subjects

Grilli, J.

Publications and source records attributed to Grilli, J..

4 recordsLinked to original sources

bioRxiv2018

Dissecting the control mechanisms for DNA replication and cell division in E. coli

Understanding how single E. coli cells coordinate the timing of cell division with genome replication would unlock a classic problem of biology, and open the way to address cell-cycle progression at the single-cell level. Several recent studies produced new data and proposed different models, based on the hypothesis that replication-segregation is the bottleneck process for cell division. However, due to the apparent contrast in both experimental results and proposed mechanisms, the emerging picture is fragmented and unclear. In this work, we re-evaluate jointly available data and models, and we show that, while each model contains useful insights, none of the proposed models, as well as generalizations based on the same assumptions, correctly describes all the correlation patterns observed in data. This analysis leads us to conclude that the assumption that replication is the bottleneck process for cell division is too restrictive. Instead, we propose that two concurrent cycles responsible for division and initiation of DNA replication together set the time of cell division. This framework correctly captures available data and allows us to select a nearly constant added size per origin between subsequent initiations as the most likely mechanism setting initiation of replication.

cell biology↗

bioRxiv2018

Concurrent processes set E. coli cell division

A cell can divide only upon completion of chromosome segregation, or its daughters would lose genetic material [1, 2]. In E. coli bacteria, the prevalent view is that cells divide a fixed amount of time after they start to copy the chromosomes [3, 4], and a known pathway prevents cells from dividing if the chromosomes interfere with the cytokinesis machinery [5]. However, whether completion of segregation is typically the bottleneck process for the decision to divide has never been stringently tested on single cells. We show how key trends in single-cell data lead to challenge the classic idea of replication-segregation limiting cell division. Instead, the data agree with a model where two concurrent processes (setting replication initiation and inter-division time) set cell division on competing time scales. During each cell cycle, division is set by the slowest process (an \" ...

cell biology↗

bioRxiv2017

An adder behavior in mammalian cells achieves size control by modulation of growth rate and cell cycle duration

Despite decades of research, it remains unclear how mammalian cell growth varies with cell size and across the cell division cycle to maintain size control. Answers have been limited by the difficulty of directly measuring growth at the single cell level. Here we report direct measurement of single cell volumes over complete cell division cycles. The volume added across the cell cycle was independent of cell birth size, a size homeostasis behavior called \"adder\". Single-cell growth curves revealed that the homeostatic behavior relied on adaptation of G1 duration as well as growth rate modulations. We developed a general mathematical framework that characterizes size homeostasis behaviors. Applying it on datasets ranging from bacteria to mammalian cells revealed that a near-adder is the most common type of size control, but only mammalian cells achieve it using modulation of both cell growth rate and cell-cycle progression.

cell biology↗

bioRxiv2017

A Point Of No Return Leading To Death During Heat-Shock In C. elegans

There is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments. Here, we studied global gene expression profiles during 12 hours of heat stress in the nematode C. elegans. Using a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3-4 hours into the stress response, separating an initially highly dynamic phase from a later relatively stagnant phase. This turning point in expression dynamics coincided with a phenotypic turning point, as shown by a strong decrease in movement, survival and, progeny count in the days following the stress. Both detectable at transcriptional and phenotypic level, this study pin-points a relatively small time frame during heat stress at which enough damage is accumulated, making it impossible to recover the next few days.

genomics↗