Navigation Links
Understanding a cell's split personality aids synthetic circuits
Date:10/4/2009

DURHAM, N.C. -- As scientists work toward making genetically altered bacteria create living "circuits" to produce a myriad of useful proteins and chemicals, they have logically assumed that the single-celled organisms would always respond to an external command in the same way.

Alas, some bacteria apparently have an individualistic streak that makes them zig when the others zag.

A new set of experiments by Duke University bioengineers has uncovered the existence of "bistability," in which an individual cell has the potential to live in either of two states, depending on which state it was in when stimulated.

Taking into account the effects of this phenomenon should greatly enhance the future efficiency of synthetic circuits, said biomedical engineer Lingchong You of Duke's Pratt School of Engineering and the Duke Institute for Genome Sciences & Policy.

In principle, re-programmed bacteria in a synthetic circuit can be useful for producing proteins, enzymes or chemicals in a coordinated way, or even delivering different types of drugs or selectively killing cancer cells, the scientists said.

Researchers in this new field of synthetic biology "program" populations of genetically altered bacteria to direct their actions in much the same way that a computer program directs a computer. In this analogy, the genetic alteration is the software, the cell the computer. The Duke researchers found that not only does the software drive the computer's actions, but the computer in turn influences the running of the software.

"In the past, synthetic biologists have often assumed that the components of the circuit would act in a predictable fashion every time and that the cells carrying the circuit would just serve as a passive reactor," You said. "In essence, they have taken a circuit-centric view for the design and optimization process. This notion is helpful in making the design process more convenient."

But it's not that simple, say You and his graduate student Cheemeng Tan, who published the results of their latest experiments early online in the journal Nature Chemical Biology.

"We found that there can be unintended consequences that haven't been appreciated before," said You. "In a population of identical cells, some can act one way while others act in another. However, this process appears to occur in a predictable manner, which allows us to take into account this effect when we design circuits."

Bistability is not unique to biology. In electrical engineering, for example, bistability describes the functioning of a toggle switch, a hinged switch that can assume either one of two positions on or off.

"The prevailing wisdom underestimated the complexity of these synthetic circuits by assuming that the genetic changes would not affect the operation of the cell itself, as if the cell were a passive chassis," said Tan. "The expression of the genetic alteration can drastically impact the cell, and therefore the circuit.

"We now know that when the circuit is activated, it affects the cell, which in turn acts as an additional feedback loop influencing the circuit," Tan said. "The consequences of this interplay have been theorized but not demonstrated experimentally."

The scientists conducted their experiments using a genetically altered colony of the bacteria Escherichia coli (E.coli) in a simple synthetic circuit. When the colony of bacteria was stimulated by external cues, some of the cells went to the "on" position and grew more slowly, while the rest went to the "off" position and grew faster.

"It is as if the colony received the command not to expand too fast when the circuit is on," Tan explained. "Now that we know that this occurs, we used computer modeling to predict how many of the cells will go to the 'on' or 'off' state, which turns out to be consistent with experimental measurements"


'/>"/>

Contact: Richard Merritt
richard.merritt@duke.edu
919-660-8414
Duke University
Source:Eurekalert

Related biology news :

1. East African cichlid fish offer new understanding of genetic basis of sex determination
2. How the 100th protein structure solved at Diamond impacts our understanding of how insects smell
3. Comprehensive understanding of bacteria could lead to new insights into many organisms
4. UNC study: Color-coded chart improves parents understanding of body mass index
5. Understanding how weeds are resistant to herbicides
6. Advance in understanding cellulose synthesis
7. Understanding plants overactive immune system will help MU researchers build better crops
8. Diminuendo -- New mouse model for understanding cause of progressive hearing loss
9. Optimum running speed is stride toward understanding human body form
10. Understanding soil carbon sequestration: New book presents key concepts
11. Understanding natural crop defenses
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/26/2016)... , April 27, 2016 ... "Global Multi-modal Biometrics Market 2016-2020"  report to their ... , The analysts forecast the global ... of 15.49% during the period 2016-2020.  ... of sectors such as the healthcare, BFSI, transportation, ...
(Date:4/13/2016)... April 13, 2016  IMPOWER physicians supporting Medicaid patients ... a new clinical standard in telehealth thanks to a ... the higi platform, IMPOWER patients can routinely track key ... body mass index, and, when they opt in, share ... visit to a local retail location at no cost. ...
(Date:3/22/2016)... , March 22, 2016 ... report "Electronic Sensors Market for Consumer Industry by Type ... Others), Application (Communication & IT, Entertainment, Home ... Global Forecast to 2022", published by MarketsandMarkets, ... expected to reach USD 26.76 Billion by ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016  Sequenom, Inc. (NASDAQ: ... healthier lives through the development of innovative products and ... the United States denied its petition ... claims of Sequenom,s U.S. Patent No. 6,258,540 (",540 Patent") ... established by the Supreme Court,s Mayo Collaborative Services v. ...
(Date:6/27/2016)... June 27, 2016  Liquid Biotech ... funding of a Sponsored Research Agreement with The ... cells (CTCs) from cancer patients.  The funding will ... levels correlate with clinical outcomes in cancer patients ... will then be employed to support the design ...
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica delle Marche in ... peritoneal or pleural mesothelioma. Their findings are the subject of a new article on ... biomarkers are signposts in the blood, lung fluid or tissue of mesothelioma patients that ...
(Date:6/23/2016)... 23, 2016 A person commits a crime, and ... to track the criminal down. An outbreak of ... Drug Administration (FDA) uses DNA evidence to track down the ... Sound far-fetched? It,s not. The FDA has increasingly used a ... of foodborne illnesses. Put as simply as possible, whole genome ...
Breaking Biology Technology: