If you were a bacterium, the virus M13 might seem innocuous enough. It
insinuates more than it invades, setting up shop like a freeloading houseguest,
not a killer. Once inside it makes itself at home, eating your food, texting
indiscriminately. Recently, however, bioengineers at Stanford University have
given M13 a bit of a makeover.

The researchers, Monica Ortiz, a doctoral candidate in bioengineering, and Drew
Endy, PhD, an assistant professor of bioengineering, have parasitized the
parasite and harnessed M13’s key attributes—its non-lethality and its ability
to package and broadcast arbitrary DNA strands—to create what might be termed
the biological Internet, or “Bi-Fi.” Their findings were published online in
the Journal of Biological Engineering.

Using the virus, Ortiz and Endy have created a biological mechanism to send
genetic messages from cell to cell. The system greatly increases the complexity
and amount of data that can be communicated between cells and could lead to
greater control of biological functions within cell communities. The advance
could prove a boon to bioengineers looking to create complex, multicellular
communities that work in concert to accomplish important biological functions.

Medium and message

M13 is a packager of genetic messages. It reproduces within its
host, taking strands of DNA—strands that engineers can control—wrapping them up
one by one and sending them out encapsulated within proteins produced by M13
that can infect other cells. Once inside the new hosts, they release the
packaged DNA message.

The M13-based system is essentially a communication channel. It acts like a
wireless Internet connection that enables cells to send or receive messages,
but it does not care what secrets the transmitted messages contain.

“Effectively, we’ve separated the message from the channel. We can now send
any DNA message we want to specific cells within a complex microbial
community,” says Ortiz, the first author of the study.

It is well known that cells naturally use various mechanisms, including
chemicals, to communicate, but such messaging can be extremely limited in both
complexity and bandwidth. Simple chemical signals are typically both message
and messenger—two functions that cannot be separated.

“If your network connection is based on sugar then your messages are limited
to ‘more sugar,’ ‘less sugar,’ or ‘no sugar,'” explains Endy.

Cells engineered with M13 can be programmed to communicate in much more
complex, powerful ways than ever before. The possible messages are limited only
by what can be encoded in DNA and thus can include any sort of genetic
instruction: start growing, stop growing, come closer, swim away, produce
insulin and so forth.

Rates and ranges

In harnessing DNA for cell-cell messaging the researchers have also greatly
increased the amount of data they can transmit at any one time. In digital
terms, they have increased the bit rate of their system. The largest DNA strand
M13 is known to have packaged includes more than 40,000 base pairs. Base pairs,
like 1s and 0s in digital encoding, are the basic building blocks of genetic
data. Most genetic messages of interest in bioengineering range from several
hundred to many thousand base pairs.

Ortiz was even able to broadcast her genetic messages between cells
separated by a gelatinous medium at a distance of greater than 7 cm.

“That’s very long-range communication, cellularly speaking,” she says. 

Down the road, the biological Internet could lead to biosynthetic factories
in which huge masses of microbes collaborate to make more complicated fuels,
pharmaceuticals and other useful chemicals. With improvements, the engineers
say, their cell-cell communication platform might someday allow more complex 3D
programming of cellular systems, including the regeneration of tissue or
organs.

“The ability to communicate ‘arbitrary’ messages is a fundamental leap—from
just a signal-and-response relationship to a true language of interaction,”
says Radhika Nagpal, professor of computer science at the Wyss Institute for
Biologically Inspired Engineering at Harvard University, who was not involved
in the research. “Orchestrating the cooperation of cells to form artificial
tissues, or even artificial organisms is just one possibility. This opens a
door to new biological systems and solving problems that have no direct analog
in nature.”

Ortiz adds, “The biological Internet is in its very earliest stages. When
the information Internet was first introduced in the 1970s, it would have been
hard to imagine the myriad uses it sees today, so there’s no telling all the
places this new work might lead.”

Source: Stanford University