‘STARS’ Help Scientists Control Genetic On/Off Switch

All life on Earth relies, ultimately, on the delicate coordination of switches. During development, these switches turn genes on—or keep them off—at precise intervals, controlling the complex processes that guide the growth of the embryo, cell by cell, as it matures from a collection of stem cells into a living, breathing organism.

Scientists have found a new way to control genetic switches.

Scientists have found a new way to control genetic switches.

If you control the switch, you could theoretically control some of life’s most fundamental processes.

Which is precisely what scientists at Cornell University are attempting to do.

Reporting in today’s issue of Nature Chemical Biology, synthetic biologists have developed a new method of directing these switches—a feat that could revolutionize the field of genetic engineering.

At the heart of the team’s discovery is a tiny molecule called RNA. A more simplified version of its cousin, DNA, RNA normally serves as a liaison—translating the genetic information housed in DNA into the proteins that together make up each and every cell in the body.

In nature, RNA does not have the ability to ‘turn on’ a gene at will. So the Cornell team, led by Julius Lucks, made a new kind of RNA that did.

They engineered a new type of RNA that they are calling Small Transcription Activating RNAs, or STARS, that can serve as a kind of artificial switch. In laboratory experiments, Lucks and his team showed that they could control how and when a gene was switched on by physically placing the STARS system in front of it. As Lucks explained in a news release:

“RNA is like a molecular puzzle, a crazy Rubik’s cube that has to be unlocked in order to do different things. We’ve figured out how to design another RNA that unlocks part of that puzzle. The STAR is the key to that lock.”

RNA is an attractive molecule to manipulate because it is so simple, says Lucks, much simpler than proteins. Many efforts aimed at protein manipulation have failed, due to the sheer complexity of these molecules. But by downshifting into the simpler, more manageable RNA molecules, Lucks argues that greater strides can be made in the field of synthetic biology and genetic engineering.

“This is going to open up a whole set of possibilities for us, because RNA molecules make decisions and compute information really well, and they detect things really well,” said Lucks.

In the future, Lucks envisions a system based solely on RNA that has the capability to manipulate genetic switches to better understand fundamental processes that guide the healthy development of a cell—and provide clues to what happens when those processes go awry.

Throwback Thursday: Scientists Create Synthetic Version of Earth’s Earliest Primordial Cells

Cells as we know them today—no matter the species—are feats of evolution; molecular machines with thousands of interlocking parts. But they didn’t start out that way.

Scientists have built a simplified cell membrane that mimics natural cellular processes and movements.

Scientists have built a simplified cell membrane that mimics natural cellular processes and movements.

Using the latest tools from the new field of synthetic biology, a team of biophysicists from Tecnische Universitaet Muenchen (TUM) in Munich, Germany, has constructed a synthetic version of an early cell, complete with some biomechanical function.

To build a primordial cell, the recipe is simple: all you need is a membrane shell, a couple of biomolecules that perform the most basic of functions, and some fuel to keep it going.

Here, TUM researchers used lipids (fat molecules) to create a double-layer cellular membrane that mimics a cell’s natural membrane. They then filled the membrane with microtubules, which acted as cellular ‘scaffolding’ to hold everything in place, and another molecule called ‘kinesin.’ These kinesin molecules serve as molecular ‘motors,’ transporting components throughout the cell by traveling along the microtubule scaffolding. Finally, they added the fuel: a compound called adenosine triphosphate, or ATP. The scientists likened this set-up to a liquid crystal layer within the membrane that is in a permanent state of motion. As lead author Felix Keber explained in a news release:

“One can picture the liquid crystal layer as tree logs drifting on the surface of a lake. When it becomes too congested, they line up in parallel but can still drift alongside each other.”

Once constructed, the research team then wanted to understand how these synthetic cells behaved, and if it would mimic natural cellular movements. And much to the team’s surprise—they did.

During a process called osmosis—where water droplets selectively pass through the membrane—the researchers noticed a change in the cells’ shape as water left the interior of the cell. The resulting membrane slack was causing the microtubules to stick out like spikes. These ‘spiked extensions’ were eerily similar to what the extensions that scientists have seen cells normally use to get around.

This observation cleared up a long-standing mystery: the way cells change shape and move around wasn’t random. The cells were simply following the basic laws of physics. This discovery then led the team to uncover the underlying mechanisms of other cellular behaviors—and even make predictions on other systems.

As the study’s lead author, Professor Andreas Bausch, stated in the same release:

“With our synthetic biomolecular model we have created a novel option for developing minimal cell models. It is ideally suited to increasing the complexity in a modular fashion in order to reconstruct cellular processes like cell migration or cell division in a controlled manner.”

In the future, the team hopes to build this knowledge to a point where they can understand the physical basis for deformed cells—with potential applications to disease modeling. Bausch added:

“That the artificially created system can be comprehensively described from a physical perspective gives us hope that in the next steps we will also be able to uncover the basic principles behind the manifold cell deformations.”