Weiss builds 'genetic circuits' for stem cell research

Electrical engineering professor Ron Weiss works with circuits, but he is never at risk of being electrocuted. His circuits are made of bacteria.

As one of the first researchers in the field of synthetic biology, Weiss conducts groundbreaking investigations focused on designing new biological functions and systems.

"Basically, we're trying to program cells just like you'd program a computer," he said. His work could have numerous applications, from producing tissues from stem cells to creating energy from photosynthetic bacteria.

Weiss' lab has engineered bacteria that can form macroscopic patterns, produce dye only when certain chemicals are present and react to their environment in novel ways.

One strain of bacteria acts like an artificial immune system. The bacteria detect the presence of certain pathogens and synthesize an enzyme to kill them.

Underlying all of these feats is a series of "genetic circuits" that use the same logic as many electronic devices. Researchers insert artificial genes created by the lab into cells, giving them a new set of instructions.

Another system being developed is a genetic toggle switch, which would allow cells to "remember" to perform an action, such as producing the dye. The toggle switch "is attractive in clinical settings ... as the continuous presence of the [chemical] is not required," Sairam Subramanian, a graduate student in the Weiss lab, said in an email.

Cells also can be engineered to communicate with each other. Bacteria can "sense" the presence of other bacteria by detecting certain chemicals and move to form patterns large enough to be seen with the naked eye.

Another of Weiss' major projects involves mouse embryonic stem cells, which could hold the key to treating some diseases.

Stem cells are characterized by their ability to differentiate into different cell types, such as skin, muscle or nerve. This ability to differentiate makes them attractive both for researching, by producing realistic models to study disease and fighting disease by producing healthy cells to replace damaged ones.

But controlling their stem cell differentiation is a major challenge.

Weiss is working on methods to program stem cells to differentiate into different tissue types. Under a certain set of conditions, stem cells can be induced to differentiate into muscle cells; in different conditions, they become nerve cells.

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"We are in the early stages of directing the differentiation of stem cells, said Dr. Priscilla Purnick, who works in the Weiss lab. The ultimate goal is "to differentiate embryonic stem cells ... with a minimum of human intervention."

Weiss' stem cell research could lead to a treatment for Type I diabetes by replacing the damaged beta cells in the pancreas that normally produce insulin. The Princeton team is trying to program stem cells to differentiate into beta cells in the correct locations in the pancreas.

"This might lead to a cure" for diabetes, Weiss said, though he emphasized that the research is "still at an early stage."

Much of the lab's work is analogous to much more complex processes occurring in nature. Stem cell differentiation already occurs during the development of all animals.

"It is quite challenging to have even a simple synthetic gene network working," Subramanian said. "It is remarkable that there are thousands of such networks perfected by nature."