Biology subjects

Grilli, J.

Publications and source records attributed to Grilli, J..

26 records · Page 2Linked to original sources

bioRxiv2021

A macroecological description of alternative stable states reproduces intra- and inter-host variability of gut microbiome

The most fundamental questions in microbial ecology concern the diversity and variability of communities. Their composition varies widely across space and time, as it is determined by a non-trivial combination of stochastic and deterministic processes. The interplay between non-linear community dynamics and environmental fluctuations determines the rich statistical structure of community variability, with both rapid temporal dynamics fluctuations and non-trivial correlations across habitats. Here we analyze long time-series of gut microbiome and compare intra- and inter-community dissimilarity. Under a macroecological framework we characterize their statistical properties. We show that most taxa have large but stationary fluctuations over time, while a minority is characterized by quick changes of average abundance which cluster in time, suggesting the presence of alternative stable states. We disentangle inter-individual variability in a major stochastic component and a deterministic one, the latter recapitulated by differences in the carrying capacities of taxa. Finally, we develop a model which includes environmental fluctuations and alternative stable states. This model quantitatively predicts the statistical properties of both intra- and inter-individual community variability, therefore summarizing variation in a unique macroecological framework.

ecology↗

bioRxiv2020

Threshold accumulation of a constitutive protein explains E. coli cell division behavior in nutrient upshifts.

Despite of a boost of recent progress in dynamic single-cell measurements and analyses in E. coli, we still lack a mechanistic understanding of the determinants of the decision to divide. Specifically, the debate is open regarding the processes linking growth and chromosome replication to division, and on the molecular origin of the observed "adder correlations", whereby cells divide adding roughly a constant volume independent of their initial volume. In order to gain insight into these questions, we interrogate dynamic size-growth behavior of single cells across nutrient upshifts with a high-precision microfluidic device. We find that the division rate changes quickly after nutrients change, much before growth rate goes to a steady state, and in a way that adder correlations are robustly conserved. Comparison of these data to simple mathematical models falsifies proposed mechanisms where replication-segregation or septum completion are the limiting step for cell division. Instead, we show that the accumulation of a putative constitutively expressed "P-sector divisor" protein explains the behavior during the shift. Significance statementThe mechanism leading to cell division in the bacterium E. coli is unknown, but we know that it results in adding a roughly constant size every cell cycle, regardless of size at birth. While most available studies try to infer information on cell division from steadily dividing cells in constant nutrient conditions, this study leverages on a high-resolution device to monitor single-cell growth division upon nutrient changes. Comparing these data with different mathematical models, the authors are able to discriminate among fundamentally different mechanisms of cell division control, and they show that the data support a model where an unregulated protein accumulates to a threshold and triggers division.

cell biology↗

bioRxiv2020

ppGpp is a bacterial cell size regulator

Growth and division are central to cell size. Bacteria achieve size homeostasis by dividing when growth has added a constant size since birth, termed the "adder" principle, by unknown mechanisms [1-4]. Growth is well known to be regulated by ppGpp, which controls anything from ribosome production to metabolic enzyme activity and replication initiation, and whose absence or excess can induce the stress response, filamentation, and yield growth-arrested miniature cells [5-8]. These observations raise unresolved questions about the relation between ppGpp and size homeostasis mechanisms during normal exponential growth. Here, to untangle effects of ppGpp and nutrients, we gained control of cellular ppGpp by inducing the synthesis and hydrolysis enzymes RelA and Mesh1. We found that ppGpp not only exerts control over the growth rate, but also over cell division and hence the steady state cell size. The added size responds rapidly to changes in the ppGpp level, aided by transiently accelerated or delayed divisions, and establishes its new constant value while the growth rate still adjusts. Moreover, the magnitude of the added size and resulting steady-state birth size correlate consistently with the ppGpp level, rather than with the growth rate, which results in cells of different size that grow equally fast. Our findings suggest that ppGpp serves as a critical regulator that coordinates cell size and growth control.

microbiology↗

bioRxiv2019

Laws of diversity and variation in microbial communities

How coexistence of many species is maintained is a fundamental and unanswered question in ecology. Coexistence is a puzzle because we lack a quantitative understanding of the variation in species presence and abundance. Whether variation in ecological communities is driven by deterministic or random processes is one of the most controversial issues in ecology. Here, we study the variation of species presence and abundance in microbial communities from a macroecological standpoint. We identify three novel, fundamental, and universal macroecological laws that characterize the fluctuation of species abundance across communities and over time. These three laws -- in addition to predicting the presence and absence of species, diversity and other commonly studied macroecological patterns -- allow to test mechanistic models and general theories aiming at describing the fundamental processes shaping microbial community composition and dynamics. We show that a mathematical model based on environmental stochasticity quantitatively predicts the three macroecological laws, as well as non-stationary properties of community dynamics.

ecology↗

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↗