scholarly journals Whole yeast model: what and why

2018 ◽  
Author(s):  
Pasquale Palumbo ◽  
Marco Vanoni ◽  
Federico Papa ◽  
Stefano Busti ◽  
Lilia Alberghina
Keyword(s):  
Life Science ◽  
Cell Model ◽  
Model Organism ◽  
Science Research ◽  
Cellular Functions ◽  
Cellular Division ◽  
Whole Cell ◽  
Proposed Model ◽  
Cell Modeling ◽  
Single Input

One of the most challenging fields in Life Science research is to deeply understand how complex cellular functions arise from the interactions of molecules in living cells. Mathematical and computational methods in Systems Biology are fundamental to study the complex molecular interactions within biological systems and to accelerate discoveries. Within this framework, a need exists to integrate different mathematical tools in order to develop quantitative models of entire organisms, i.e. whole-cell models. This note presents a first attempt to show the feasibility of such a task for the budding yeast Saccharomyces cerevisiae, a model organism for eukaryotic cells: the proposed model refers to the main cellular activities like metabolism, growth and cycle in a modular fashion, therefore allowing to treat them separately as single input/output modules, as well as to interconnect them in order to build the backbone of a coarse-grain whole cell model. The model modularity allows to substitute a low granularity module with one with a finer grain, whenever molecular details are required to correctly reproduce specific experiments. Furthermore, by properly setting the cellular division, simulations of cell populations are achieved, able to deal with protein distributions. Whole cell modeling will help understanding logic of cell resilience.

scholarly journals Whole yeast model: what and why

2018 ◽  
Author(s):  
Pasquale Palumbo ◽  
Marco Vanoni ◽  
Federico Papa ◽  
Stefano Busti ◽  
Lilia Alberghina
Keyword(s):  
Life Science ◽  
Cell Model ◽  
Model Organism ◽  
Science Research ◽  
Cellular Functions ◽  
Cellular Division ◽  
Whole Cell ◽  
Proposed Model ◽  
Cell Modeling ◽  
Single Input

One of the most challenging fields in Life Science research is to deeply understand how complex cellular functions arise from the interactions of molecules in living cells. Mathematical and computational methods in Systems Biology are fundamental to study the complex molecular interactions within biological systems and to accelerate discoveries. Within this framework, a need exists to integrate different mathematical tools in order to develop quantitative models of entire organisms, i.e. whole-cell models. This note presents a first attempt to show the feasibility of such a task for the budding yeast Saccharomyces cerevisiae, a model organism for eukaryotic cells: the proposed model refers to the main cellular activities like metabolism, growth and cycle in a modular fashion, therefore allowing to treat them separately as single input/output modules, as well as to interconnect them in order to build the backbone of a coarse-grain whole cell model. The model modularity allows to substitute a low granularity module with one with a finer grain, whenever molecular details are required to correctly reproduce specific experiments. Furthermore, by properly setting the cellular division, simulations of cell populations are achieved, able to deal with protein distributions. Whole cell modeling will help understanding logic of cell resilience.

The E. coli Whole-Cell Modeling Project

EcoSal Plus ◽  
2021 ◽  
Author(s):  
Gwanggyu Sun ◽  
Travis A. Ahn-Horst ◽  
Markus W. Covert
Keyword(s):  
Computational Model ◽  
Model Organism ◽  
Current Version ◽  
Whole Cell ◽  
Content Type ◽  
E Coli ◽  
Cell Modeling

The Escherichia coli whole-cell modeling project seeks to create the most detailed computational model of an E. coli cell in order to better understand and predict the behavior of this model organism. Details about the approach, framework, and current version of the model are discussed.

scholarly journals Testing theoretical minimal genomes using whole-cell models

2020 ◽  
Author(s):  
Joshua Rees-Garbutt ◽  
Jake Rightmyer ◽  
Oliver Chalkley ◽  
Lucia Marucci ◽  
Claire Grierson
Keyword(s):  
In Silico ◽  
Cell Model ◽  
Mycoplasma Genitalium ◽  
Essential Genes ◽  
Cellular Division ◽  
Whole Cell ◽  
Gene Sets ◽  
Dividing Cells ◽  
Species Specific

AbstractThe minimal gene set for life has often been theorised, with at least ten produced for Mycoplasma genitalium (M. genitalium). Due to the difficulty of using M. genitalium in the lab, combined with its long replication time of 12 - 15 hours, none of these theoretical minimal genomes have been tested, even with modern techniques. The publication of the M. genitalium whole-cell model provided the first opportunity to test them, simulating the genome edits in-silico. We simulated eight minimal gene sets from the literature, finding that they produced in-silico cells that did not divide. Using knowledge from previous research, we reintroduced specific essential and low essential genes in-silico; enabling cellular division. This reinforces the need to identify species-specific low essential genes and their interactions. Any genome designs created using the currently incomplete and fragmented gene essentiality information, will very likely require in-vivo reintroductions to correct issues and produce dividing cells.

scholarly journals On the Relation between Chemical Oscillations and Self-Replication

2017 ◽  
Vol 23 (4) ◽  
pp. 453-480
Author(s):  
Erwan Bigan ◽  
Pierre Plateau
Keyword(s):  
Cell Model ◽  
Nonlinear Differential Equations ◽  
Oscillation Amplitude ◽  
Volume Ratio ◽  
Spontaneous Curvature ◽  
Model Framework ◽  
Cellular Division ◽  
Chemical Oscillations ◽  
Biochemical Oscillations ◽  
Self Replication

One proposed scenario for the emergence of biochemical oscillations is that they may have provided the basic mechanism behind cellular self-replication by growth and division. However, alternative scenarios not requiring any chemical oscillation have also been proposed. Each of the various protocell models proposed to support one or another scenario comes with its own set of specific assumptions, which makes it difficult to ascertain whether chemical oscillations are required or not for cellular self-replication. This article compares these two cases within a single whole-cell model framework. This model relies upon a membrane embedding a chemical reaction network (CRN) synthesizing all the cellular constituents, including the membrane, by feeding from an external nutrient. Assuming the osmolarity is kept constant, the system dynamics are governed by a set of nonlinear differential equations coupling the chemical concentrations and the surface-area-to-volume ratio. The resulting asymptotic trajectories are used to determine the cellular shape by minimizing the membrane bending energy (within an approximate predefined family of shapes). While the stationary case can be handled quite generally, the oscillatory one is investigated using a simple oscillating CRN example, which is used to identify features that are expected to hold for any network. It is found that cellular self-replication can be reached with or without chemical oscillations, and that a requirement common to both stationary and oscillatory cases is that a minimum spontaneous curvature of the membrane is required for the cell to divide once its area and volume are both doubled. The oscillatory case can result in a greater variety of cellular shape trajectories but raises additional constraints for cellular division and self-replication: (i) the ratio of doubling time to oscillation period should be an integer, and (ii) if the oscillation amplitude is sufficiently high, then the spontaneous curvature must be below a maximum value to avoid early division before the end of the cycle. Because of these additional stringent constraints, it is likely that early protocells did not rely upon chemical oscillations. Biochemical oscillations typical of modern evolved cells may have emerged later through evolution for other reasons (e.g., metabolic advantage) and must have required additional feedback mechanisms for such a self-replicating system to be robust against even slight environmental variations (e.g., temperature fluctuations).

The principles of whole-cell modeling

2015 ◽  
Vol 27 ◽  
pp. 18-24 ◽  
Author(s):  
Jonathan R Karr ◽  
Koichi Takahashi ◽  
Akira Funahashi
Keyword(s):  
Whole Cell ◽  
Cell Modeling

scholarly journals The Road Less Traveled? Unconventional Protein Secretion at Parasite–Host Interfaces

2021 ◽  
Vol 9 ◽  
Author(s):  
Erina A. Balmer ◽  
Carmen Faso
Keyword(s):  
Protein Secretion ◽  
Cell Biology ◽  
Mammalian Cells ◽  
Cell Model ◽  
Signal Sequence ◽  
Model Organism ◽  
Secreted Proteins ◽  
Current Status ◽  
Secretory Proteins ◽  
Secretion Pathways

Protein secretion in eukaryotic cells is a well-studied process, which has been known for decades and is dealt with by any standard cell biology textbook. However, over the past 20 years, several studies led to the realization that protein secretion as a process might not be as uniform among different cargos as once thought. While in classic canonical secretion proteins carry a signal sequence, the secretory or surface proteome of several organisms demonstrated a lack of such signals in several secreted proteins. Other proteins were found to indeed carry a leader sequence, but simply circumvent the Golgi apparatus, which in canonical secretion is generally responsible for the modification and sorting of secretory proteins after their passage through the endoplasmic reticulum (ER). These alternative mechanisms of protein translocation to, or across, the plasma membrane were collectively termed “unconventional protein secretion” (UPS). To date, many research groups have studied UPS in their respective model organism of choice, with surprising reports on the proportion of unconventionally secreted proteins and their crucial roles for the cell and survival of the organism. Involved in processes such as immune responses and cell proliferation, and including far more different cargo proteins in different organisms than anyone had expected, unconventional secretion does not seem so unconventional after all. Alongside mammalian cells, much work on this topic has been done on protist parasites, including genera Leishmania, Trypanosoma, Plasmodium, Trichomonas, Giardia, and Entamoeba. Studies on protein secretion have mainly focused on parasite-derived virulence factors as a main source of pathogenicity for hosts. Given their need to secrete a variety of substrates, which may not be compatible with canonical secretion pathways, the study of mechanisms for alternative secretion pathways is particularly interesting in protist parasites. In this review, we provide an overview on the current status of knowledge on UPS in parasitic protists preceded by a brief overview of UPS in the mammalian cell model with a focus on IL-1β and FGF-2 as paradigmatic UPS substrates.

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