scholarly journals Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Giansimone Perrino ◽  
Sara Napolitano ◽  
Francesca Galdi ◽  
Antonella La Regina ◽  
Davide Fiore ◽  
...  

AbstractThe cell cycle is the process by which eukaryotic cells replicate. Yeast cells cycle asynchronously with each cell in the population budding at a different time. Although there are several experimental approaches to synchronise cells, these usually work only in the short-term. Here, we build a cyber-genetic system to achieve long-term synchronisation of the cell population, by interfacing genetically modified yeast cells with a computer by means of microfluidics to dynamically change medium, and a microscope to estimate cell cycle phases of individual cells. The computer implements a controller algorithm to decide when, and for how long, to change the growth medium to synchronise the cell-cycle across the population. Our work builds upon solid theoretical foundations provided by Control Engineering. In addition to providing an avenue for yeast cell cycle synchronisation, our work shows that control engineering can be used to automatically steer complex biological processes towards desired behaviours similarly to what is currently done with robots and autonomous vehicles.

2020 ◽  
Author(s):  
Giansimone Perrino ◽  
Sara Napolitano ◽  
Francesca Galdi ◽  
Antonella La Regina ◽  
Davide Fiore ◽  
...  

ABSTRACTThe cell cycle is the process by which eukaryotic cells replicate. Yeast cells cycle asynchronously with each cell in the population budding at a different time. Although there are several experimental approaches to “synchronise” cells, these work only in the short-term. Here, we built a cyber-genetic system to achieve long-term synchronisation of the cell population, by interfacing genetically modified yeast cells with a computer by means of microfluidics to dynamically change medium, and a microscope to estimate cell cycle phases of individual cells. The computer implements a “controller” algorithm to decide when, and for how long, to change the growth medium to synchronise the cell-cycle across the population. Our work builds upon solid theoretical foundations provided by Control Engineering. In addition to providing a new avenue for yeast cell cycle synchronisation, our work shows that computers can automatically steer complex biological processes towards desired behaviours similarly to what is currently done with robots and autonomous vehicles.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3161
Author(s):  
Mahsa Ebrahimi ◽  
Lukas Habernig ◽  
Filomena Broeskamp ◽  
Andreas Aufschnaiter ◽  
Jutta Diessl ◽  
...  

Nutrient limitation results in an activation of autophagy in organisms ranging from yeast, nematodes and flies to mammals. Several evolutionary conserved nutrient-sensing kinases are critical for efficient adaptation of yeast cells to glucose, nitrogen or phosphate depletion, subsequent cell-cycle exit and the regulation of autophagy. Here, we demonstrate that phosphate restriction results in a prominent extension of yeast lifespan that requires the coordinated activity of autophagy and the multivesicular body pathway, enabling efficient turnover of cytoplasmic and plasma membrane cargo. While the multivesicular body pathway was essential during the early days of aging, autophagy contributed to long-term survival at later days. The cyclin-dependent kinase Pho85 was critical for phosphate restriction-induced autophagy and full lifespan extension. In contrast, when cell-cycle exit was triggered by exhaustion of glucose instead of phosphate, Pho85 and its cyclin, Pho80, functioned as negative regulators of autophagy and lifespan. The storage of phosphate in form of polyphosphate was completely dispensable to in sustaining viability under phosphate restriction. Collectively, our results identify the multifunctional, nutrient-sensing kinase Pho85 as critical modulator of longevity that differentially coordinates the autophagic response to distinct kinds of starvation.


Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 81
Author(s):  
Nisrin El Mlili ◽  
Hanan Ahabrach ◽  
Omar Cauli

Cortisol is the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and its production is increased mainly in stressful situations or in chronic disorders accompanied by stress enhancement. Altered cortisol concentrations have been reported in a number of neuropsychiatric diseases and sleep disorders. Cortisol concentrations have been measured using several methods, and in several matrixes, such as blood, saliva, and urine. However, lately, hair cortisol, for several reasons, has emerged as a promising biomarker of long-term retrospective HPA activation. Several experimental approaches for cortisol measurement with the corresponding concentration reference ranges and a summary of findings from scientific literature on this field are presented. There is evidence of a close relationship between HPA functional alteration and the development of neuropsychiatric disorders. Sleep disorders are the most common manifestation in several neuropsychiatric conditions, and have also been associated to cortisol alterations in both adults and children. Many studies indicate that hair cortisol constitutes a valuable tool for further contributing to existing data on salivary, plasma, or urinary cortisol concentrations in patients with sleep disorders.


Lab on a Chip ◽  
2021 ◽  
Author(s):  
Ningquan Wang ◽  
Ruxiu Liu ◽  
Norh Asmare ◽  
Chia-Heng Chu ◽  
Ozgun Civelekoglu ◽  
...  

An adaptive microfluidic system changing its operational state in real-time based on cell measurements through an on-chip electrical sensor network.


Small Science ◽  
2021 ◽  
pp. 2100002
Author(s):  
Tomohito Sekine ◽  
Yi-Fei Wang ◽  
Jinseo Hong ◽  
Yasunori Takeda ◽  
Reo Miura ◽  
...  

2021 ◽  
pp. 1-10
Author(s):  
Karissa Barthelson ◽  
Stephen Martin Pederson ◽  
Morgan Newman ◽  
Haowei Jiang ◽  
Michael Lardelli

Background: Mutations in PRESENILIN 2 (PSEN2) cause early onset familial Alzheimer’s disease (EOfAD) but their mode of action remains elusive. One consistent observation for all PRESENILIN gene mutations causing EOfAD is that a transcript is produced with a reading frame terminated by the normal stop codon—the “reading frame preservation rule”. Mutations that do not obey this rule do not cause the disease. The reasons for this are debated. Objective: To predict cellular functions affected by heterozygosity for a frameshift, or a reading frame-preserving mutation in zebrafish psen2 using bioinformatic techniques. Methods: A frameshift mutation (psen2N140fs) and a reading frame-preserving (in-frame) mutation (psen2T141 _ L142delinsMISLISV) were previously isolated during genome editing directed at the N140 codon of zebrafish psen2 (equivalent to N141 of human PSEN2). We mated a pair of fish heterozygous for each mutation to generate a family of siblings including wild type and heterozygous mutant genotypes. Transcriptomes from young adult (6 months) brains of these genotypes were analyzed. Results: The in-frame mutation uniquely caused subtle, but statistically significant, changes to expression of genes involved in oxidative phosphorylation, long-term potentiation and the cell cycle. The frameshift mutation uniquely affected genes involved in Notch and MAPK signaling, extracellular matrix receptor interactions and focal adhesion. Both mutations affected ribosomal protein gene expression but in opposite directions. Conclusion: A frameshift and an in-frame mutation at the same position in zebrafish psen2 cause discrete effects. Changes in oxidative phosphorylation, long-term potentiation and the cell cycle may promote EOfAD pathogenesis in humans.


2001 ◽  
Vol 21 (5) ◽  
pp. 1710-1718 ◽  
Author(s):  
David J. Galgoczy ◽  
David P. Toczyski

ABSTRACT Despite the fact that eukaryotic cells enlist checkpoints to block cell cycle progression when their DNA is damaged, cells still undergo frequent genetic rearrangements, both spontaneously and in response to genotoxic agents. We and others have previously characterized a phenomenon (adaptation) in which yeast cells that are arrested at a DNA damage checkpoint eventually override this arrest and reenter the cell cycle, despite the fact that they have not repaired the DNA damage that elicited the arrest. Here, we use mutants that are defective in checkpoint adaptation to show that adaptation is important for achieving the highest possible viability after exposure to DNA-damaging agents, but it also acts as an entrée into some forms of genomic instability. Specifically, the spontaneous and X-ray-induced frequencies of chromosome loss, translocations, and a repair process called break-induced replication occur at significantly reduced rates in adaptation-defective mutants. This indicates that these events occur after a cell has first arrested at the checkpoint and then adapted to that arrest. Because malignant progression frequently involves loss of genes that function in DNA repair, adaptation may promote tumorigenesis by allowing genomic instability to occur in the absence of repair.


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