Redesigning cells

(Nanowerk News) It had been seven years since Fahim Farzadfard had last seen his family back home in Iran. Even after obtaining his green card in the middle of 2016, he had waited to finish his PhD before making the trip. Finally, last December, Farzadfard made a long-awaited visit to his hometown of Mashhad, Iran.
Farzadfard had missed his family, and would have loved to stay longer to enjoy Persian cuisine, Iran’s raw beauty, and the courteous culture he grew up with. He kept his visit short, however, partly out of concerns over a possible travel ban under the new federal administration, but also because of the ongoing research at MIT that he was devoted to. Even while in Iran, he had been working on it to the best of his ability, but he soon felt pulled to return to campus.
 Fahim Farzadfard in the lab
“We engineer new functions into cells. We try to give them new abilities,” PhD student Fahim Farzadfard says. “Basically, we’re making molecular tools. We try to understand cells inner-workings and engineer them using these tools.” (Photo: M. Scott Brauer)
Farzadfard came to MIT almost seven years ago, after completing his undergraduate and master’s degrees in biotechnology from a prestigious program at the University of Tehran. It was in this program that Farzadfard would fall twice in love — with biological engineering and with a fellow student, Nava Gharaei, whom he would later marry.
While at the University of Tehran, Fahim was committed to his research but understood that the academic labs in Iran had limited resources. That meant research projects would take much longer and be more difficult to accomplish. Something that would take a month to complete in the United States, Fahim says, might take a year in Iran.
“I wanted to do cutting edge research,” he says. “The opportunity wasn’t there.”
Fahim decided that if he wanted to excel further in the emerging field of synthetic biology, he would need to seek opportunities outside of his home country. Weeks after he and Gharaei defended their master’s theses, they got married and landed in Boston to start a new journey as PhD students — she at Harvard University and he in the Synthetic Biology Group in MIT’s Research Laboratory of Electronics.

Master tinkerers

Synthetic biology is a relatively new field that marries engineering with molecular and cellular biology. As Farzardfard explains it, scientists tinker with existing biological parts and systems to redesign a cell’s functionality. “We engineer new functions into cells. We try to give them new abilities,” he says. “Basically, we’re making molecular tools. We try to understand cells’ inner-workings and engineer them using these tools.”
Farzadfard has been taking synthetic biology to the next level by engineering an analog memory storage system using the cell’s DNA. Living cells are constantly sensing their environment, sampling molecules and computing a response based on their genetic programs and the environmental cues that they recieve. For example, when pancreatic cells sense a high concentration of glucose (input), this starts a chain reaction of regulatory and signaling molecules (cell processing), that eventually leads to the production and release of insulin (output).
In synthetic biology, genes can be designed and engineered to respond to signaling molecules and to regulate the expression of other genes in such a way that they could perform logic functions. Analogous to computer circuits, these interconnected networks of genes are called gene circuits and can be used to engineer and program cellular functions. Someday, engineered cells with these circuits could find a number of uses, such as sensors for environmental or medical monitoring.
In 2014, Farzadfard and Timothy Lu, MIT associate professor of electrical engineering and computer science and of biological engineering, published their findings in Science. Previous studies had demonstrated that memory can be encoded in DNA, but the encodings were “digital” — that is, they recorded only whether a particular event occurred. Farzadfard’s platform overcomes this limitation by making analog recordings, which capture information about an event’s intensity, for example, or its duration.
“You can have infinite states. The capacity to record analog information means you can record the magnitude of inputs, not just absence or presence,” Farzadfard says, “You can record how much input and how long it has been there.”
Farzadfard has also been working to develop a sort of DNA barcode memory system in bacteria that are communicating with one another. In this research, two different bacteria, A and B, were given their own DNA barcodes. Farzadfard developed a system where if bacteria A and B communicate via conjugation (a transfer of DNA), then a new barcode, AB, would be encoded in their DNA. The logic seems simple and straightforward, but it has the potential for mapping cellular interactions at single-cell resolution. For example, this technique might someday be used to map all the connections of a network of neurons, Farzardfard says.

Caught between two countries

After the 2016 presidential election, Farzadfard remembers being concerned about potential policy changes from the new administration that could affect people living in the U.S., based on their nationalities. Those concerns increased when President Trump first signed an executive order preventing individuals from Iran and certain other countries from entering the United States, and the status of green-card holders was unclear. Farzadfard was thankful to have had the foresight to visit Iran last December, but he acknowledges that many others are worried about being able to travel to their home countries.
“Personally, I didn’t experience that much hardship after the election,” he says. “I’m lucky. Some of my friends couldn’t come those few days after [the president’s executive order]. I could have easily been one of those people, and had that stress of the uncertainty of not knowing what is going to happen next.”
At that time, he wondered when he would next be able to visit his three sisters, his parents, or once again enjoy delicious Persian food which, he jokingly says, caused him to gain a few pounds that he hasn’t lost yet. Now that judges from federal district courts have blocked the revised version of President Trump’s executive order, Farzadfard feels more confident about traveling to Iran and having the freedom to return to America.
Whatever the future may hold, this soft-spoken Iranian immigrant has come a long way since first arriving in America without knowing anyone but his wife. Today, he’s made many friends and has established his life in New England, while continuing to push the frontiers of synthetic biology.
Source: By Dara Farhadi, MIT