Navigation Links
Understanding a cell's split personality aids synthetic circuits

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
Duke University

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:
(Date:10/4/2017)... , Oct. 4, 2017  GCE Solutions, a global clinical ... data and document anonymization solution on October 4, 2017. Shadow is ... field to comply with policy 0070 of the European Medicines Agency ... data. ... GCE Solutions ...
(Date:7/20/2017)... , July 20, 2017 Delta (NYSE: DAL ) ... any Delta aircraft at Reagan Washington National Airport (DCA). ... Delta launches biometrics to board ... Delta,s biometric boarding ... Club is now integrated into the boarding process to allow eligible ...
(Date:6/14/2017)... -- IBM (NYSE: IBM ) is introducing several innovative partner ... developing collaboration between startups and global businesses, taking place in ... event, nine startups will showcase the solutions they have built ... France is one of ... 30 percent increase in the number of startups created between ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... AMRI, a global contract ... to improve patient outcomes and quality of life, will now be offering its ... attributed to new regulatory requirements for all new drug products, including the finalization ...
(Date:10/11/2017)... (PRWEB) , ... October 11, 2017 , ... ... Foundation President Andi Purple announced Dr. Suneel I. Sheikh, the co-founder, CEO ... ASTER Labs ), Inc. has been selected for membership in ARCS Alumni ...
(Date:10/11/2017)... ... October 11, 2017 , ... Personal eye wash is a basic first aid supply for any ... So which eye do you rinse first if a dangerous substance enters both eyes? It’s ... Wash with its unique dual eye piece. , “Whether its dirt and debris, or ...
(Date:10/11/2017)... ... 2017 , ... Proscia Inc ., a data solutions ... “Pathology is going digital. Is your lab ready?” with Dr. Nicolas Cacciabeve, Managing ... how Proscia improves lab economics and realizes an increase in diagnostic confidence.* ...
Breaking Biology Technology: