The goal of the emerging field of synthetic biology is to produce and assemble biological parts and to create new life forms that will have a positive effect on people or the environment. Reaching that goal will require the experts of several disciplines, from biology and chemistry to computer science and engineering. The likely payoff for scientists with the required expertise is a high probability of fascinating science, both basic and applied. The field is so new that there are few dedicated training programs, but interested scientists have found their own ways into the field, as these three scientists–a microbiologist, a mechanical engineer, and a chemist–explain to Science Careers.
A microbiologist in search of applications
Early on, Radha Krishnakumar’s plan was to study the mechanisms by which bacteria cause disease and to find new methods to combat them. This plan, and her innate scientific curiosity, led her to acquire a wide range of scientific skills. Her desire to apply those skills to something practical led to her current job at the J. Craig Venter Institute (JCVI) in Rockville, Maryland.
Krishnakumar, 33, earned a master’s degree in microbiology at Bharathidasan University in Tiruchirappalli, a city in her native India. In 2000, she started work on a Ph.D. at the University of Illinois, Urbana-Champaign, on the gastroenteritis-causing ability of Salmonella. She was looking at the role of an enzyme called copper/zinc superoxide dismutase in Salmonella’s virulence. Soon, she also decided to peer into the structure-function relationship of this enzyme.
After she finished her graduate work, an ad for a position in synthetic biology at JCVI caught her eye. Krishnakumar joined JCVI in 2006. Since then, the group has taken some important steps toward building a synthetic cell, transplanting the whole genome of one species of bacteria into another species of bacteria, and synthesizing the entire Mycoplasma genitalium genome. “Now what we want to do is try to boot up this artificial genome into a cell and see if we can jump-start life,” Krishnakumar says.
Krishnakumar’s main project is building a new strain of Mycoplasma that produces proteins with more than the standard 20 amino acids nature uses. Such a bug could be used to produce non-natural proteins with, say, novel antimicrobial properties, Krishnakumar says. But it also helps the lab to mitigate risk. “When we make a synthetic cell, we want to make it so that it cannot survive in the absence of the 21st amino acid,” Krishnakumar says. That way, the organism won’t be able to survive outside the lab.
The ultimate goal–synthetic life–is exciting in itself, but Krishnakumar most enjoys the excitement of the quest. “It is a very new field, and every day people are coming up with new ideas” and new techniques for building genes and metabolic pathways, she says. It’s exciting and challenging work–but the greatest challenges she encounters are away from the lab. It’s “challenging for us to make the public understand [that] what we are doing is not harmful,” she says.
Choosing synthetic biology for a postdoc, Krishnakumar says, was “a risky move.” But today, as she contemplates applying her synthetic biology skills to the production of antimicrobial compounds in a pharmaceutical or biotech company, she believes her opportunities are expanding.
A diversifying mechanical engineer
British-Canadian Kim de Mora, 26, has always enjoyed mechanical things. Yet, during the penultimate year of his mechanical engineering master’s degree at the University of Edinburgh in the U.K., de Mora realized he didn’t want a “pure mechanical engineering” career.
In 2006, as he considered research topics for his Ph.D. and looked for something to do over the summer, de Mora got an e-mail from the biomedical engineer who was to become his Ph.D. supervisor, calling on undergrads to join the Edinburgh team for the international Genetically Engineered Machine (iGEM) competition (see Getting Ready for Synthetic Biology), an annual contest in which teams around the world tackle a synthetic-biology challenge. His interest piqued, de Mora joined a team of eight engineering, biology, and informatics undergrads and four faculty members. In the 10 weeks that followed, the team built a simple biological device able to detect arsenic in drinking water and won the 2006 iGEM prize for the best real-world application.
De Mora was hooked. “I was really surprised that after that amount of time our device … worked, and that’s what really got me interested. … I thought, ‘If that’s what nine undergrads can do in a summer, what can you do with this for your career?’ ” He decided to pursue synthetic biology for his dissertation topic.
Being in a biomedical engineering lab with no molecular biology expertise, de Mora was given carte blanche on which synthetic biology project he wanted to tackle. He set out to design a new strain of yeast that would be able to detect glucose and release insulin–the first draft of a synthetic pancreas. “I came up with a rough idea of how I could do it, like which were the genes that I would need to look at,” de Mora says. But he soon learned that not “all the pathways that I was looking at are all completely understood and known. I could just about make the yeast responsive to glucose but not at the correct concentration ranges.”
Hoping to get some help from synthetic biologists, de Mora went to Pamela Silver’s lab at Harvard Medical School’s Systems Biology Department in Boston on a 6-month travel scholarship from the Royal Society of Edinburgh. Once there, he decided to switch projects to fit in better with Silver’s lab. He started engineering the production in yeast of human copies of small organelles called peroxisomes. He plans to stay in Silver’s lab, living off his own savings, until he finishes all his experiments.
An engineer by training, de Mora had to learn many general biology and molecular biology skills. “I found it initially difficult and a little bit overwhelming at times,” he says. But “if you want to interact between the people modeling and developing tools and the people that are actually using those tools–the biologists–then I think engineering helps,” de Mora says. “It allows you to understand … what exactly the problems are and try to solve them.”
To those interested in exploring the field, “the best way in right now … is iGEM,” the MIT-sponsored competition, he says. “That will really show you what’s possible, what’s going on in the field, … and whether you want to pursue it.”
A chemist following natural evolution
As a teenager, Stano was drawn to chemistry because he saw it as the most rigorous way to investigate natural compounds. His interest in analysis led him toward chemical synthesis: At the University of Pisa in Italy, he explored supramolecules, synthesizing transition metal complexes as part of his master’s degree research project. Since then, biology, too, has been shifting from analysis toward synthesis, he says, so it was natural to apply his supramolecular knowledge to “try to synthesize biological systems.”
After receiving his master’s degree, Stano became a research assistant in Pier Luigi Luisi’s group in the material science department of the Swiss Federal Institute of Technology Zurich. There, he started using molecular self-organization to build lipid vesicles for drug delivery.
Lipid vesicles may also be used as small bioreactors that “have the same structure [as] a cell,” Stano explains. “We call them minimal cells … because they should contain the minimal number of components that produce a behavior [or] function very similar to cells.” Stano’s line of research merged with synthetic biology, and in 2004, Luisi offered him another research assistant position, in the biology department of the Roma Tre University back in Italy, where Luisi is now mainly based.
Since January, Stano has been involved in the European SynthCells project, which aims to develop new approaches to engineering synthetic minimal cells. Because minimal cells are so simple, they can serve as models for the original cell, he explains. “We study how these cells grow, how they reproduce, how they interact with … polymers, for example RNA [and] proteins,” Stano says.
To work in synthetic biology, Stano relies heavily on his background as a chemist. “For my chemical mentality, constructing the thing you want to study is natural, because in chemistry you build molecules,” he says. Another similarity: “The process of building is extremely useful because it lets you understand many things.”
Stano works alongside chemists, biologists, and mathematicians. There’s even “a philosopher in our group because we should ask ‘What is life?’ and when our minimal cell is alive.” Indeed, one of the greatest challenges in synthetic biology is communication with scientists from other disciplines. You have “to find common ways to describe things and to work together,” Stano says. Another great challenge is that it is still very difficult to control systems at the molecular level and get them to do what you want, Stano adds.
But with these challenges comes the excitement of being a pioneer in an important, emerging field. Synthetic biology is “so young that there are no classical views,” he says. Synthetic biology, Stano argues, will be one of the foundations of science and technology in the 21st century thanks to its new, powerful “systems” perspective. “If you look at the parts, you don’t see anything. But if the parts are connected together by some organization, you can see something that emerges. This is life.”
Photos, top to bottom: PhotoDisc, Michael G. Montague, courtesy of Kim de Mora, courtesy of Pasquale Stano.