But now experts at the Florida Company of Engineering (Caltech) are obtaining that tissue can answer using a new kind of boasting procedure, instead of just shifting from one continuous condition to another and being there. The guidelines behind this process are interestingly simple, the experts say, and could generate other cellular phone methods, disclosing more about how the tissue -- and eventually life -- work.
In their research, the experts researched how a microbial types known as B. subtilis behaves to a demanding atmosphere -- for example, one without food. In such problems, the single-celled patient triggers a large set of genetics that help it handle problems, by helping cellular fix for example. In the past, scientists had imagined the germs would manage tension by transforming on the appropriate genetics and simply making them on until the tension goes away.
Instead, the experts found that B. subtilis consistently flicks these genetics on and off. When encountered with more tension, it raises the rate of these impulses. The boasting actions is like shifting your heating unit on full boost for a brief period every few moments, and transforming it on and off more generally if you want the home to be hotter.
"It's a very different view of how a cell can respond to a particular stress," says James Locke, a postdoctoral scholar at Caltech. Locke and graduate student Jonathan Young are the lead authors on a paper describing this work, which was published in the Oct. 21 issue of Science.
To make their finding, the researchers introduced a chemical to B. subtilis that inhibits the production of ATP, the energy-carrying molecules of cells. The team found that the stress induced by this chemical triggers interactions within a set of genes -- collectively called a genetic circuit. This circuit, which contains a set of positive and negative feedback loops, generates sustained pulses of activity in a key regulatory protein called σB ("sigma B"). The researchers attached fluorescent proteins to the circuit, causing the cells to glow green when σB was activated. By making movies of the flashing cells, the team could then study the dynamics of the circuit.
The key to this pulsating mechanism is the variability inherent in how proteins are made, the researchers say. The number of copies of any specific protein in a given cell fluctuates over time. The bacterial gene circuit amplifies these molecular fluctuations, also called noise, to generate discrete pulses of σB activation. The stress also activates another key protein that modulates the pulse frequencies.
By turning a steady input (the stress) into an oscillating output (the activation of σB) the genetic circuit is analogous to an electrical inverter, a device that converts direct current (DC) into alternating current (AC), explains Michael Elowitz, professor of biology and bioengineering at Caltech, Howard Hughes Medical Institute investigator, and coauthor of the paper. "You might think you need some kind of elaborate circuitry to implement that, but the cell can do it with just a few proteins, and by taking advantage of noise."
This work provides a blueprint for how relatively simple genetic circuits can generate complex and dynamic behaviors in individual cells, the researchers say. "We're excited to think that similar mechanisms may occur in other cellular processes," Locke says. "It'd be interesting in the future to see which aspects of this circuit architecture also appear in more complex systems, such as mammalian cells."
"With this work and recent work in other systems, we're starting to get a glimpse of just how dynamic cellular control systems really are," Elowitz adds. "That's something that was very difficult to see in the past."
The other authors of the Science paper, "Stochastic pulse regulation in bacterial stress response," are research technicians Michelle Fontes and Maria Jesus Hernandez Jimenez. The research was funded by the National Institutes of Health, the National Science Foundation, the Packard Foundation, the International Human Frontier Science Organization, and the European Molecular Biology Organization.
