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Math Model Accurately Mimics Cell Division In Carbon-cycling Bacterium
ScienceDaily (Aug. 22, 2009) — Scientists from the Department of Biological Sciences and the Virginia Bioinformatics Institute (VBI) at Virginia Tech have developed a quantitative, mathematical model of DNA replication and cell division for the bacterium Caulobacter crescentus. C. crescentus, an alpha-proteobacterium that inhabits freshwater, seawater and soils, is an ideal organism for genetic and computational biology studies due to the wealth of molecular information that has been accumulated by researchers. It also plays a key role in global carbon cycling in its natural environment.
See also:
Plants & Animals
* Developmental Biology
* Cell Biology
* Molecular Biology
Computers & Math
* Computer Modeling
* Mathematical Modeling
* Mathematics
Reference
* Vector (biology)
* Microorganism
* Computational genomics
* Trait (biology)
The researchers work will appear in the August 14 edition of PLoS Computational Biology. The article is by Genetics, Bioinformatics, and Computational Biology graduate student Shenghua Li, research scientist Paul Brazhnik, Professor and Director of VBI's Cyberinfrastructure Group Bruno Sobral, and University Distinguished Professor of Biological Sciences John Tyson.
The mathematical model described in the paper allows researchers to study and analyze the systems-level dynamics of the Caulobacter cell cycle, test hypotheses and suggest crucial new experiments. "By careful examination of the large amount of experimental information available about the genes, proteins and biochemical reactions involved in regulating the cell division of C. crescentus, we have developed a good understanding of the mechanism of cell division in this organism and a realistic, quantitative mathematical model of the molecular machinery that oversees Caulobacter's cell division cycle," said John Tyson.
Caulobacter normally undergoes a cell cycle that produces two different types of offspring: a motile "swarmer cell" with a flagellum, a slender thread-like structure that allows the bacterium to swim, and an immobile "sessile stalked cell" that lacks a flagellum. The two cell types undergo different development programs but share the same core molecular regulatory system that controls whether the cell commits to a new round of DNA synthesis and to the cell division process. This regulatory core comprises three key proteins – DnaA, GcrA, and CtrA – that act as control points or master switches for DNA replication and cell division. The new math model allows scientists to investigate how these proteins vary with time and their link to physiological events in both stalked and swarmer cells.
"Cells have some similarities to computers in the sense that they engage in information processing", said Tyson. "However, prokaryotic cells like Caulobacter have been somewhat neglected as information systems in studies by scientists. While computers are precise, digital processors, cells are analog systems that operate for the most part in sloppy, watery environments. Conveying instructions for DNA replication and cell division has profound consequences for a cell and needs to be done with considerable accuracy and precision and that's one of the reasons why we want to be able to model the process." Tyson added: "We have been able to establish a wiring diagram that maps the essential regulatory steps for DNA replication and cell division in Caulobacter in a way that is similar to how you would define a computer process. The model provides a rigorous account of the consequences of our hypotheses, which can be compared to experimental observations to test the model."
With the model in place, the researchers confirmed that it correctly represents the sequence of physiological events that take place during cell division. They were able to show in simulations that the model accurately describes how the different proteins change in quantity during the cell division cycle. Taking this one step further, they were also able to simulate the impact of specific known mutations on cell function.
Mutant cells provide valuable information about how individual components of the cell cycle control system affect the features (phenotype) of cells. Commented Tyson: "Our model allows you to perform quantitative predictions for novel mutants. We have performed simulations of some novel mutants that to our knowledge have not been described in the scientific literature. For example, the math model predicts that if the master regulator CtrA cannot be properly phosphorylated, which is a key step in the activation of CtrA, then the cell replicates its DNA but cannot divide. It will grow very long and eventually die. Specific predictions like this can test the reliability of the model. A validated model can then be used to design new experiments by in silico simulations."
The researchers have built a math model that allows for the study of how the protein components change with time. Future versions of the model will also take into account the spatial localization of the proteins. Said Bruno Sobral: "Caulobacter crescentus is a member of the alpha-proteobacteria, a group of diverse organisms whose members have successfully adopted different lifestyle and energy-yielding strategies over the course of evolution. Caulobacter was also recently detected as a human pathogen, which makes its study directly relevant to human health. Since many genes and mechanisms discovered in Caulobacter are evolutionarily conserved among the alpha-proteobacteria our computational model of cell replication may be applicable to other family members, in particular the causative agents of brucellosis in cattle and Rocky Mountain spotted fever in humans."
Journal reference:
1. Shenghua Li, Paul Brazhnik, Bruno Sobral, John J. Tyson. Temporal controls of the asymmetric cell division cycle in Caulobacter crescentus. PLoS Computational Biology, 2009; 5(8): e1000463 DOI: 10.1371/journal.pcbi.1000463
Adapted from materials provided by Virginia Tech, via EurekAlert!, a service of AAAS.
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Virginia Tech (2009, August 22). Math Model Accurately Mimics Cell Division In Carbon-cycling Bacterium. ScienceDaily. Retrieved August 24, 2009, from http://www.sciencedaily.com /releases/2009/08/090813202124.htm
enlarge
Two cells of the aquatic bacterium Caulobacter crescentus attach to a surface, and each other, by their glue-secreting holdfasts. The holdfast is the structure at the tip of the stalk, a thin extension of the cell. The two cells in the picture are about to divide. (Credit: Yves V. Brun, Indiana University)
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Related Stories
Biologists Use Computers To Study Bacterial Cell Division (Jan. 30, 2008) — A group of computational biologists have created a mathematical model of the process that regulates cell division in a common bacterium, confirming hypotheses, providing new insights, identifying ... > read more
Nature's Strongest Glue Could Be Used As A Medical Adhesive (Apr. 12, 2006) — A bacterium that lives in rivers, streams and human aqueducts uses nature's strongest glue to stay in one place, according to new research by Indiana University Bloomington and Brown University ... > read more
How Do Bacteria Swim? Physicists Explain (Nov. 20, 2008) — Physicists have completed the most detailed study of the swimming patterns of a microbe, showing for the first time how its movement is affected by drag and a phenomenon called Brownian ... > read more
Carbon Metabolism And DNA Replication Tightly Linked, Study Finds (May 17, 2007) — A challenging goal in biology is to understand how principal cellular functions are integrated so that cells achieve viability and optimal fitness under a wide range of nutritional conditions. ... > read more
Bacteria Are Models Of Efficiency (Feb. 6, 2009) — A mathematical model has revealed how single celled organisms regulate their activities for maximum ... > read more
Figuring Out Function From Bacteria's Bewildering Forms (July 19, 2006) — The constellation of shapes and sizes among bacteria is as remarkable as it is mysterious. Why should Spirochaeta halophila resemble a bedspring coil, Stella a star and Clostridium cocleatum a partly ... > read more
Puzzle In The Control Of Cell Division Unraveled (July 5, 2008) — A puzzle in the control of cell division, one of the most fundamental processes in all biology, has been unraveled. Although the steps of cell division are familiar to all pupils studying biology in ... > read more
Researchers Succeed In Observing For First Time How DNA Damage Is Identified (May 22, 2006) — For the first time anywhere, researchers at the Hebrew University of Jerusalem have succeeded in observing and describing how damaged DNA is naturally ... > read more
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Math Model Accurately Mimics Cell Division In Carbon-cycling Bacterium
ScienceDaily (Aug. 22, 2009) — Scientists from the Department of Biological Sciences and the Virginia Bioinformatics Institute (VBI) at Virginia Tech have developed a quantitative, mathematical model of DNA replication and cell division for the bacterium Caulobacter crescentus. C. crescentus, an alpha-proteobacterium that inhabits freshwater, seawater and soils, is an ideal organism for genetic and computational biology studies due to the wealth of molecular information that has been accumulated by researchers. It also plays a key role in global carbon cycling in its natural environment.
See also:
Plants & Animals
* Developmental Biology
* Cell Biology
* Molecular Biology
Computers & Math
* Computer Modeling
* Mathematical Modeling
* Mathematics
Reference
* Vector (biology)
* Microorganism
* Computational genomics
* Trait (biology)
The researchers work will appear in the August 14 edition of PLoS Computational Biology. The article is by Genetics, Bioinformatics, and Computational Biology graduate student Shenghua Li, research scientist Paul Brazhnik, Professor and Director of VBI's Cyberinfrastructure Group Bruno Sobral, and University Distinguished Professor of Biological Sciences John Tyson.
The mathematical model described in the paper allows researchers to study and analyze the systems-level dynamics of the Caulobacter cell cycle, test hypotheses and suggest crucial new experiments. "By careful examination of the large amount of experimental information available about the genes, proteins and biochemical reactions involved in regulating the cell division of C. crescentus, we have developed a good understanding of the mechanism of cell division in this organism and a realistic, quantitative mathematical model of the molecular machinery that oversees Caulobacter's cell division cycle," said John Tyson.
Caulobacter normally undergoes a cell cycle that produces two different types of offspring: a motile "swarmer cell" with a flagellum, a slender thread-like structure that allows the bacterium to swim, and an immobile "sessile stalked cell" that lacks a flagellum. The two cell types undergo different development programs but share the same core molecular regulatory system that controls whether the cell commits to a new round of DNA synthesis and to the cell division process. This regulatory core comprises three key proteins – DnaA, GcrA, and CtrA – that act as control points or master switches for DNA replication and cell division. The new math model allows scientists to investigate how these proteins vary with time and their link to physiological events in both stalked and swarmer cells.
"Cells have some similarities to computers in the sense that they engage in information processing", said Tyson. "However, prokaryotic cells like Caulobacter have been somewhat neglected as information systems in studies by scientists. While computers are precise, digital processors, cells are analog systems that operate for the most part in sloppy, watery environments. Conveying instructions for DNA replication and cell division has profound consequences for a cell and needs to be done with considerable accuracy and precision and that's one of the reasons why we want to be able to model the process." Tyson added: "We have been able to establish a wiring diagram that maps the essential regulatory steps for DNA replication and cell division in Caulobacter in a way that is similar to how you would define a computer process. The model provides a rigorous account of the consequences of our hypotheses, which can be compared to experimental observations to test the model."
With the model in place, the researchers confirmed that it correctly represents the sequence of physiological events that take place during cell division. They were able to show in simulations that the model accurately describes how the different proteins change in quantity during the cell division cycle. Taking this one step further, they were also able to simulate the impact of specific known mutations on cell function.
Mutant cells provide valuable information about how individual components of the cell cycle control system affect the features (phenotype) of cells. Commented Tyson: "Our model allows you to perform quantitative predictions for novel mutants. We have performed simulations of some novel mutants that to our knowledge have not been described in the scientific literature. For example, the math model predicts that if the master regulator CtrA cannot be properly phosphorylated, which is a key step in the activation of CtrA, then the cell replicates its DNA but cannot divide. It will grow very long and eventually die. Specific predictions like this can test the reliability of the model. A validated model can then be used to design new experiments by in silico simulations."
The researchers have built a math model that allows for the study of how the protein components change with time. Future versions of the model will also take into account the spatial localization of the proteins. Said Bruno Sobral: "Caulobacter crescentus is a member of the alpha-proteobacteria, a group of diverse organisms whose members have successfully adopted different lifestyle and energy-yielding strategies over the course of evolution. Caulobacter was also recently detected as a human pathogen, which makes its study directly relevant to human health. Since many genes and mechanisms discovered in Caulobacter are evolutionarily conserved among the alpha-proteobacteria our computational model of cell replication may be applicable to other family members, in particular the causative agents of brucellosis in cattle and Rocky Mountain spotted fever in humans."
Journal reference:
1. Shenghua Li, Paul Brazhnik, Bruno Sobral, John J. Tyson. Temporal controls of the asymmetric cell division cycle in Caulobacter crescentus. PLoS Computational Biology, 2009; 5(8): e1000463 DOI: 10.1371/journal.pcbi.1000463
Adapted from materials provided by Virginia Tech, via EurekAlert!, a service of AAAS.
Email or share this story:
| More
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
Virginia Tech (2009, August 22). Math Model Accurately Mimics Cell Division In Carbon-cycling Bacterium. ScienceDaily. Retrieved August 24, 2009, from http://www.sciencedaily.com /releases/2009/08/090813202124.htm
enlarge
Two cells of the aquatic bacterium Caulobacter crescentus attach to a surface, and each other, by their glue-secreting holdfasts. The holdfast is the structure at the tip of the stalk, a thin extension of the cell. The two cells in the picture are about to divide. (Credit: Yves V. Brun, Indiana University)
Ads by Google
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Framework 7
Register for your free online training course
agilent.com/chem/framework7online
Problems with Mycoplasma?
MycoSPY for detection-MycoRAZOR for removal-mycofree Trypsin,FBS
www.biontex.com
Moartea microscopica
Un virus necrutator ameninta femeile. Afla mai mult!
www.informarehpv.ro
Reliable Cell Analysis
Reduce cell variability with cell micropatterns
www.cytoo.com
Systems Biology&Medicine
Wiley Interdisciplinary Reviews Free Access Opt-in NOW!
www.wiley.com/wires/sysbio
Related Stories
Biologists Use Computers To Study Bacterial Cell Division (Jan. 30, 2008) — A group of computational biologists have created a mathematical model of the process that regulates cell division in a common bacterium, confirming hypotheses, providing new insights, identifying ... > read more
Nature's Strongest Glue Could Be Used As A Medical Adhesive (Apr. 12, 2006) — A bacterium that lives in rivers, streams and human aqueducts uses nature's strongest glue to stay in one place, according to new research by Indiana University Bloomington and Brown University ... > read more
How Do Bacteria Swim? Physicists Explain (Nov. 20, 2008) — Physicists have completed the most detailed study of the swimming patterns of a microbe, showing for the first time how its movement is affected by drag and a phenomenon called Brownian ... > read more
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Figuring Out Function From Bacteria's Bewildering Forms (July 19, 2006) — The constellation of shapes and sizes among bacteria is as remarkable as it is mysterious. Why should Spirochaeta halophila resemble a bedspring coil, Stella a star and Clostridium cocleatum a partly ... > read more
Puzzle In The Control Of Cell Division Unraveled (July 5, 2008) — A puzzle in the control of cell division, one of the most fundamental processes in all biology, has been unraveled. Although the steps of cell division are familiar to all pupils studying biology in ... > read more
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Search ScienceDaily
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Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily's archives for related news topics,
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Int. Diabetes Monitor
A free online review journal on trends in clinical diabetes.
InternationalDiabetesMonitor.com
Used Biotech Instruments
PCR/RT PCR, DNA seq(ABI3730,3100) Storm860/Typhoon9400. Centrifuge
www.cgenetool.com
Food Production Decon
Decontaminate food manufacturing and food preparation facilities
www.Bioquell.co.uk
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Microchip Does 1,000 Chemical Reactions At Once
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Inner 'Fingerprint' For Personal Medical Care
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Oxycholesterol: Greatest Heart Disease Risk?
Science Video News
Cancer Killer Found In The Ocean
Biomedicine scientists identified and sequenced the genes of a bacteria called Salinispora tropica. It produces anti-cancer compounds and can be. ... > full story
* Bioengineers Combine Mathematical Equations, Data to Simulate Surgeries
* Physicist Explains Benefits Of Carbon Dioxide
* Meteorologists See Future of Increasingly Extreme Weather Events
* more science videos
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* S.Korea seeks 4-year prison term for stem cell fraud
* Encyclopedia of Life grows; clues on ageing, pests
* Satellites put into orbit for Japan and Australia
* Scientists make "sugar bug" drug for bowel disease
* Gene swap experiment makes altering bugs easier
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In Other News ...
* Suspect in U.S. model murder found dead in Canada
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* Malaysian state to cane woman after Ramadan
* U.S. presses sanctions to end N.Korea atomic plans
* Singapore shoots down "rumor" of APEC attack plot
* Hurricane Bill kills 2 in U.S., drenches eastern Canada
* China trials over Xinjiang riot "likely this week"
* Warner Chilcott to buy P&G unit for $3 billion: sources
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